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• Original Investigation Non–High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events Feitong Wu, PhD; David R. Jacobs, PhD; Stephen R. Daniels, MD, PhD; et al cme

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Research articles

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse, esketamine after childbirth for mothers with prenatal depression, glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer, use of progestogens and the risk of intracranial meningioma, delirium and incident dementia in hospital patients, derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin, quality and safety of artificial intelligence generated health information, large language models and the generation of health disinformation, 25 year trends in cancer incidence and mortality among adults in the uk, cervical pessary versus vaginal progesterone in women with a singleton pregnancy, comparison of prior authorization across insurers, diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis, ultra-processed food exposure and adverse health outcomes, added benefit and revenues of oncology drugs approved by the ema, exposure to air pollution and hospital admission for cardiovascular diseases, short term exposure to low level ambient fine particulate matter and natural cause, cardiovascular, and respiratory morbidity, optimal timing of influenza vaccination in young children, effect of exercise for depression, association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes, duration of cpr and outcomes for adults with in-hospital cardiac arrest, clinical effectiveness of an online physical and mental health rehabilitation programme for post-covid-19 condition, atypia detected during breast screening and subsequent development of cancer, publishers’ and journals’ instructions to authors on use of generative ai in academic and scientific publishing, effectiveness of glp-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes, neurological development in children born moderately or late preterm, invasive breast cancer and breast cancer death after non-screen detected ductal carcinoma in situ, all cause and cause specific mortality in obsessive-compulsive disorder, acute rehabilitation following traumatic anterior shoulder dislocation, perinatal depression and risk of mortality, undisclosed financial conflicts of interest in dsm-5-tr, effect of risk mitigation guidance opioid and stimulant dispensations on mortality and acute care visits, update to living systematic review on sars-cov-2 positivity in offspring and timing of mother-to-child transmission, perinatal depression and its health impact, christmas 2023: common healthcare related instruments subjected to magnetic attraction study, using autoregressive integrated moving average models for time series analysis of observational data, demand for morning after pill following new year holiday, christmas 2023: christmas recipes from the great british bake off, effect of a doctor working during the festive period on population health: experiment using doctor who episodes, christmas 2023: analysis of barbie medical and science career dolls, christmas 2023: effect of chair placement on physicians’ behavior and patients’ satisfaction, management of chronic pain secondary to temporomandibular disorders, christmas 2023: projecting complete redaction of clinical trial protocols, christmas 2023: a drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing, christmas 2023: efficacy of cola ingestion for oesophageal food bolus impaction, conservative management versus laparoscopic cholecystectomy in adults with gallstone disease, social media use and health risk behaviours in young people, untreated cervical intraepithelial neoplasia grade 2 and cervical cancer, air pollution deaths attributable to fossil fuels, implementation of a high sensitivity cardiac troponin i assay and risk of myocardial infarction or death at five years, covid-19 vaccine effectiveness against post-covid-19 condition, association between patient-surgeon gender concordance and mortality after surgery, intravascular imaging guided versus coronary angiography guided percutaneous coronary intervention, treatment of lower urinary tract symptoms in men in primary care using a conservative intervention, autism intervention meta-analysis of early childhood studies, effectiveness of the live zoster vaccine during the 10 years following vaccination, effects of a multimodal intervention in primary care to reduce second line antibiotic prescriptions for urinary tract infections in women, pyrotinib versus placebo in combination with trastuzumab and docetaxel in patients with her2 positive metastatic breast cancer, association of dcis size and margin status with risk of developing breast cancer post-treatment, racial differences in low value care among older patients in the us, pharmaceutical industry payments and delivery of low value cancer drugs, rosuvastatin versus atorvastatin in adults with coronary artery disease, clinical effectiveness of septoplasty versus medical management for nasal airways obstruction, ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder, early versus delayed antihypertensive treatment in patients with acute ischaemic stroke, mortality risks associated with floods in 761 communities worldwide, interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities, association between changes in carbohydrate intake and long term weight changes, future-case control crossover analysis for adjusting bias in case crossover studies, association between recently raised anticholinergic burden and risk of acute cardiovascular events, suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: individual participant data meta-analysis, efficacy and safety of an inactivated virus-particle vaccine for sars-cov-2, effect of invitation letter in language of origin on screening attendance: randomised controlled trial in breastscreen norway, visits by nurse practitioners and physician assistants in the usa, non-erosive gastro-oesophageal reflux disease and oesophageal adenocarcinoma, venous thromboembolism with use of hormonal contraception and nsaids, food additive emulsifiers and risk of cardiovascular disease, balancing risks and benefits of cannabis use, promoting activity, independence, and stability in early dementia and mild cognitive impairment, effect of home cook interventions for salt reduction in china, cancer mortality after low dose exposure to ionising radiation, effect of a smartphone intervention among university students with unhealthy alcohol use, long term risk of death and readmission after hospital admission with covid-19 among older adults, mortality rates among patients successfully treated for hepatitis c, association between antenatal corticosteroids and risk of serious infection in children, the proportions of term or late preterm births after exposure to early antenatal corticosteroids, and outcomes, safety of ba.4-5 or ba.1 bivalent mrna booster vaccines, comparative effectiveness of booster vaccines among adults aged ≥50 years, third dose vaccine schedules against severe covid-19 during omicron predominance in nordic countries, private equity ownership and impacts on health outcomes, costs, and quality, healthcare disruption due to covid-19 and avoidable hospital admission, educational inequalities in mortality and their mediators among generations across four decades, prevalence and predictors of data and code sharing in the medical and health sciences, medicare eligibility and in-hospital treatment patterns and health outcomes for patients with trauma, therapeutic value of first versus supplemental indications of drugs in us and europe, hospital admissions linked to sars-cov-2 infection in children and adolescents, vitamin d supplementation and major cardiovascular events, menopausal hormone therapy and dementia, associations between modest reductions in kidney function and adverse outcomes in young adults, association between surgeon volume and patient outcomes after elective shoulder replacement surgery, risk prediction of covid-19 related death or hospital admission in adults testing positive for sars-cov-2, follow us on, content links.

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Page 1 of 32

Correction: A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis

The original article was published in Journal of Biomedical Science 2022 29 :24

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Significance of hepatitis B virus capsid dephosphorylation via polymerase

It is generally believed that hepatitis B virus (HBV) core protein (HBc) dephosphorylation (de-P) is important for viral DNA synthesis and virion secretion. HBV polymerase contains four domains for terminal pr...

Association of TRAIL receptor with phosphatase SHP-1 enables repressing T cell receptor signaling and T cell activation through inactivating Lck

T cell receptor (TCR) signaling and T cell activation are tightly regulated by gatekeepers to maintain immune tolerance and avoid autoimmunity. The TRAIL receptor (TRAIL-R) is a TNF-family death receptor that ...

Improving CRISPR–Cas9 directed faithful transgene integration outcomes by reducing unwanted random DNA integration

The field of genome editing has been revolutionized by the development of an easily programmable editing tool, the CRISPR–Cas9. Despite its promise, off-target activity of Cas9 posed a great disadvantage for g...

A matter of new life and cell death: programmed cell death in the mammalian ovary

The mammalian ovary is a unique organ that displays a distinctive feature of cyclic changes throughout the entire reproductive period. The estrous/menstrual cycles are associated with drastic functional and mo...

Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury

Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The mi...

The rise of big data: deep sequencing-driven computational methods are transforming the landscape of synthetic antibody design

Synthetic antibodies (Abs) represent a category of artificial proteins capable of closely emulating the functions of natural Abs. Their in vitro production eliminates the need for an immunological response, st...

Tick-borne encephalitis virus transmitted singly and in duo with Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum bacteria by ticks as pathogens modifying lipid metabolism in human blood

Ticks are vectors of various pathogens, including tick-borne encephalitis virus causing TBE and bacteria such as Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum causing e.g. viral-bacterial co-infec...

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional ...

Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes

Streptococcus pyogenes (group A streptococcus, GAS) causes a variety of diseases ranging from mild superficial infections of the throat and skin to severe invasive infections, such as necrotizing soft tissue infe...

Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications

Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming of energy metabolism is a major feature of the malignant transformation of breast cancer. Compar...

Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson’s disease phenotypes in vivo and in cell models

Mutations in CHCHD2 have been linked to Parkinson’s disease, however, their exact pathophysiologic roles are unclear. The p32 protein has been suggested to interact with CHCHD2, however, the physiological functio...

The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tu...

Translational research on drug development and biomarker discovery for hepatocellular carcinoma

Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist in this field because of the limited availability of hum...

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan

Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population.

Rab37 mediates trafficking and membrane presentation of PD-1 to sustain T cell exhaustion in lung cancer

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor expressed on the surface of T cells. High expression of PD-1 leads to T-cell dysfunction in the tumor microenvironment (TME). However, th...

FLT3L-induced virtual memory CD8 T cells engage the immune system against tumors

Previous research in FMS-like tyrosine kinase 3 ligands (FLT3L) has primarily focused on their potential to generate dendritic cells (DCs) from bone marrow progenitors, with a limited understanding of how thes...

Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus

Mycobacterium abscessus , a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic ...

Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy

MDM2 has been established as a biomarker indicating poor prognosis for individuals undergoing immune checkpoint inhibitor (ICI) treatment for different malignancies by various pancancer studies. Specifically, ...

Mechanisms and functions of SUMOylation in health and disease: a review focusing on immune cells

SUMOylation, which is a type of post-translational modification that involves covalent conjugation of small ubiquitin-like modifier (SUMO) proteins to target substrates, regulates various important molecular a...

Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice

CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longe...

Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma

The expression of aquaporin 4 (AQP4) and intermediate filament (IF) proteins is altered in malignant glioblastoma (GBM), yet the expression of the major IF-based cytolinker, plectin (PLEC), and its contributio...

Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool

Cancer remains a serious burden in society and while the pace in the development of novel and more effective therapeutics is increasing, testing platforms that faithfully mimic the tumor microenvironment are l...

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-β activity through its receptor stability in dermal fibroblasts

Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathol...

Physiology and pharmacological targeting of phase separation

Liquid–liquid phase separation (LLPS) in biology describes a process by which proteins form membraneless condensates within a cellular compartment when conditions are met, including the concentration and postt...

Inactivation of pentraxin 3 suppresses M2-like macrophage activity and immunosuppression in colon cancer

The tumor microenvironment is characterized by inflammation-like and immunosuppression situations. Although cancer-associated fibroblasts (CAFs) are among the major stromal cell types in various solid cancers,...

Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines

Extracellular vesicles (EVs) are tiny, lipid membrane-bound structures that are released by most cells. They play a vital role in facilitating intercellular communication by delivering bioactive cargoes to rec...

Attenuation of neurovirulence of chikungunya virus by a single amino acid mutation in viral E2 envelope protein

Chikungunya virus (CHIKV) has reemerged as a major public health concern, causing chikungunya fever with increasing cases and neurological complications.

Scaffold-based 3D cell culture models in cancer research

Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer c...

Therapeutic antibodies for the prevention and treatment of cancer

The developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the an...

Immune evasion in cell-based immunotherapy: unraveling challenges and novel strategies

Cell-based immunotherapies (CBIs), notably exemplified by chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy, have emerged as groundbreaking approaches for cancer therapy. Nevertheless, akin to ...

Exploring the relationship between metabolism and immune microenvironment in osteosarcoma based on metabolic pathways

Metabolic remodeling and changes in tumor immune microenvironment (TIME) in osteosarcoma are important factors affecting prognosis and treatment. However, the relationship between metabolism and TIME needs to ...

The synergism of cytosolic acidosis and reduced NAD + /NADH ratio is responsible for lactic acidosis-induced vascular smooth muscle cell impairment in sepsis

During sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in vasoplegia, hypotension and hypoperfusion. In ad...

Localization, traffic and function of Rab34 in adipocyte lipid and endocrine functions

Excessive lipid accumulation in the adipose tissue in obesity alters the endocrine and energy storage functions of adipocytes. Adipocyte lipid droplets represent key organelles coordinating lipid storage and m...

Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer

As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with other the...

A novel mucosal bivalent vaccine of EV-A71/EV-D68 adjuvanted with polysaccharides from Ganoderma lucidum protects mice against EV-A71 and EV-D68 lethal challenge

Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in chi...

A secreted form of chorismate mutase (Rv1885c) in Mycobacterium bovis BCG contributes to pathogenesis by inhibiting mitochondria-mediated apoptotic cell death of macrophages

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and its pathogenicity is associated with its ability to evade the host defense system. The secretory form of the chorismate mutase of M. tub...

ARID1A loss activates MAPK signaling via DUSP4 downregulation

ARID1A , a tumor suppressor gene encoding BAF250, a protein participating in chromatin remodeling, is frequently mutated in endometrium-related malignancies, including ovarian or uterine clear cell carcinoma (CCC)...

SCEL regulates switches between pro-survival and apoptosis of the TNF-α/TNFR1/NF-κB/c-FLIP axis to control lung colonization of triple negative breast cancer

Patients with metastatic triple-negative breast cancer (mTNBC) have a higher probability of developing visceral metastasis within 5 years after the initial diagnosis. Therefore, a deeper understanding of the p...

Butterflies in the gut: the interplay between intestinal microbiota and stress

Psychological stress is a global issue that affects at least one-third of the population worldwide and increases the risk of numerous psychiatric disorders. Accumulating evidence suggests that the gut and its ...

Spatiotemporal roles of AMPK in PARP-1- and autophagy-dependent retinal pigment epithelial cell death caused by UVA

Although stimulating autophagy caused by UV has been widely demonstrated in skin cells to exert cell protection, it remains unknown the cellular events in UVA-treated retinal pigment epithelial (RPE) cells.

The ‘speck’-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a s...

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies

Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can b...

Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges

RNA has emerged as a revolutionary and important tool in the battle against emerging infectious diseases, with roles extending beyond its applications in vaccines, in which it is used in the response to the CO...

Human ACE2 protein is a molecular switch controlling the mode of SARS-CoV-2 transmission

Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the lungs and is upregulated after SAR...

Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis

Mitochondrial mass and quality are tightly regulated by two essential and opposing mechanisms, mitochondrial biogenesis (mitobiogenesis) and mitophagy, in response to cellular energy needs and other cellular a...

Extracellular release in the quality control of the mammalian mitochondria

Mammalian cells release a wealth of materials to their surroundings. Emerging data suggest these materials can even be mitochondria with perturbed morphology and aberrant function. These dysfunctional mitochon...

mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high e...

Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update

Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis of AD involves various pathophysiological events, including the accumulation o...

Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations

Mitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally inherited with 37 genes, encoding 13 poly...

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Health & Medicine News

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Revolutionising health care: Exploring the latest advances in medical sciences

Gehendra mahara.

1 Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China

4 Shantou University Medical College, Shantou, Guangdong, China

Cuihong Tian

2 Center for Precision Health, Edith Cowan University, Perth, Australia

3 Department of Cardiovascular Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China

5 Department of Infection Control, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangzhou, China

Photo: Human heart, anterior view, artificial valve, coronary bypass. Illustration by Patrick J. Lynch. Source: Flickr, free to use under Creative Commons Attribution 2.5 License ( https://creativecommons.org/licenses/by/2.5/ ).

Recent years have seen a revolution in the domain of medical science, with ground-breaking discoveries changing health care as we once knew it [ 1 ]. These advances have considerably improved disease diagnosis, treatment, and management, improving patient outcomes and quality of life [ 2 - 5 ]. These innovations range from the creation of novel medications and treatments to the utilization of cutting-edge technologies. For instance, gene editing technologies like Clustered Regularly Interspaced Palindromic Repeats (CRISPR-Cas9) have opened up new treatment options for genetic illnesses [ 6 ], while the development of mRNA vaccines has offered a desperately needed response to the coronavirus disease 2019 (COVID-19) pandemic [ 7 ]. Moreover, wearable technology and telemedicine have improved accessibility, convenience, and personalization of health care, whereas 3D printing and nanotechnology breakthroughs have made it possible to create individualized implants and drug delivery systems [ 8 - 10 ]. This article examines some of the most recent developments in medical research and how they might completely change health care delivery.

The selection process for identifying the latest advances in medical sciences for this article was as follows. We aimed to showcase ground-breaking developments with the potential to revolutionise health care practices and significantly impact patient outcomes. We extensively searched reputable scientific journals, conferences, and reports from recognized health care organisations and institutes. We included the novelty and significance of the advancements, their ability to address existing health care challenges, the level of scientific evidence supporting their efficacy, and their potential for widespread adoption and implementation. By utilizing this process, we ensured that the selected advancements represent diverse medical fields and have the capacity to drive significant advancements in patient care, diagnostics, treatment modalities, and health care delivery.

REGENERATIVE THERAPY TREATMENT

Regenerative medicine is a rapidly growing field that seeks to restore, replace, or regenerate damaged tissues and organs using a variety of approaches, including cell therapy, tissue engineering, and gene therapy [ 11 ]. This field has the potential to revolutionise the treatment of many diseases and injuries that are currently incurable or difficult to treat. For example, stem cell therapy has been shown to be effective in treating spinal cord injuries [ 12 ], with several studies reporting significant improvements in motor function and sensory perception [ 13 ]. Tissue engineering approaches are being developed to replace damaged or diseased organs using 3D printing, such as the liver, pancreas, and heart [ 11 , 14 ]. Gene therapy is being used to target genetic disorders, such as sickle cell anaemia and cystic fibrosis, with promising results [ 15 ]. The development of regenerative medicine has the potential to transform the treatment of many diseases and injuries, providing hope for patients with conditions that are currently considered untreatable [ 16 - 18 ].

DEVELOPMENT OF IMPLANTABLE ARTIFICIAL ORGANS

Various replacement or augmentation devices for organs, such as the eyes, kidneys, heart, muscle, liver, skin, and brain, have been developed due to the creation of implantable artificial organs [ 4 ]. Artificial organs can be developed from a number of substances, such as polymers and biological tissues, and are intended to mimic the shape and functionality of actual organs [ 19 ]. For instance, the Wearable Artificial Kidney (WAK) has promise for enhancing the quality of life for individuals with end-stage of renal illness [ 20 ]. The creation of artificial hearts ( Figure 1 ), such as the Total Artificial Heart (TAH), has the potential to extend the lives of patients awaiting heart transplants [ 21 - 23 ].

Artificial Intelligence, Brain. Image by Gerd Altmann. Source: Pixabay, free to use under Content License ( https://pixabay.com/service/license-summary/ ).

Furthermore, scientists are developing artificial muscles, liver tissue replicas, skin grafts, and brain implants. For instance, a study by Kolesky et al. [ 24 ] reported the successful implantation of a 3D-printed artificial skin graft. Additionally, a study by White [ 25 ] and Weng et al. [ 26 ] revealed the development of a 3D-printed muscle tissue construct [ 26 ]. Although the research into implantable artificial organs is still in its infancy, it has the potential to transform how organ failure is treated and enhance patient outcomes [ 4 ].

ADVANCEMENTS IN NANOTECHNOLOGY IN HEALTH SCIENCE

Another fast-expanding and highly promising area of use for nanotechnology is in the field of medicine. Drugs and other therapeutic substances can be delivered directly to a disease site using nanoparticles because they can target particular cells or tissues in the body [ 27 ]. This technology may improve the efficacy of therapies, lessen their negative effects, and potentially enable the treatment of previously incurable diseases [ 28 ].

Current developments in nanotechnology have demonstrated considerable promise for the medical field. A study by Foglizzo and Marchio [ 10 ] created a multifunctional nano platform that delivered chemotherapeutic medication and an immunomodulatory substance to tumour cells, increasing antitumor activity and minimizing adverse effects. Using nanotechnology, a magnetic resonance imaging (MRI) contrast agent that can specifically target and image pancreatic cancer cells was created [ 29 ]. Moreover, nanotechnology has demonstrated promise in the treatment of diseases like brain tumours that were previously incurable. A study by Chen et al. [ 30 ] created a nano platform that specifically targeted and delivered medications to brain tumour cells, improving survival rates in a mouse model. These recent developments show how nanotechnology has the potential to enhance therapeutic efficacy, lessen adverse effects, and broaden the scope of diseases that can be treated [ 31 , 32 ].

DEVELOPMENT OF CRISPR-Cas9 GENE EDITING TECHNOLOGY

A rapidly developing technique called gene editing could revolutionise medicine by enabling researchers to change cells' genetic makeup. CRISPR-Cas9, a promising method for gene editing, allows for accurate targeting and editing of particular regions of the genome [ 33 ]. Genetic disorders like cystic fibrosis and sickle cell anaemia, which were once thought to be incurable, could potentially be cured because of this technique [ 34 , 35 ]. Also, scientists are looking at its therapeutic potential for a number of illnesses, such as Alzheimer’s disease, human immunodeficiency virus (HIV), and cancer [ 34 , 36 ].

Yet there are also moral questions raised by using gene editing on people, so it's important to use the technology sensibly and morally. Until the hazards and moral issues surrounding germline editing, which edits the genes that can be passed on to future generations, are better known, a group of scientists called for a moratorium on its clinical usage in 2019 [ 37 ].

ARTIFICIAL INTELLIGENCE (AI) FOR MEDICAL SCIENCE

Recent years have seen considerable advancements in the use of artificial intelligence (AI) and machine learning in the health care industry. In order to find trends and forecast health outcomes, AI systems can evaluate enormous amounts of medical data, including images, test results, and patient records [ 38 ]. This may result in more accurate diagnosis, individualized treatment strategies, and effective patient monitoring.

The promise of AI in health care has been proved by a number of studies. For instance, Esteva et al. [ 39 ], created an AI model with skin cancer detection accuracy on par with dermatologists. Rajkomar et al. [ 40 ] use of machine learning to forecast patient mortality and hospital readmission rates may aid health care professionals in identifying patients who need more care. Moreover, Chung et al. [ 41 ], created an AI algorithm that could anticipate the onset of psychosis in individuals who had clinical high-risk signs.

Predicting the risk of cardiovascular illness using AI has also shown promise. For example, Khera et al. [ 42 ] developed a model using machine learning to identify patients with a high risk of developing heart disease, potentially allowing for early intervention and preventative measures.

Yet, there are also issues with using AI in health care that need to be resolved, such as the requirement for strong data protection and ethical concerns with the use of AI algorithms to clinical decision-making [ 43 ].

CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY TO TREAT CANCER

Chimeric Antigen Receptor (CAR) T-cell therapy, a form of immunotherapy that employs T cells to recognize and target cancer cells, depends heavily on genetically transformed T cells [ 44 ]. Recent studies have demonstrated that CAR T treatment is very effective in treating a range of lymphoma types, including diffuse large B-cell lymphoma and mantle cell lymphoma [ 45 , 46 ].

Despite the positive outcomes, CAR T therapy has drawbacks, such as a high price and risk for toxicity. In order to increase the effectiveness and safety of CAR T treatment and broaden its use to treat additional cancer types, research is now being done by Ren et al. [ 47 ]. For instance, a recent study by Yang et al. [ 48 ] discovered that multiple myeloma, a kind of blood cancer, that has relapsed or become resistant to treatment, can be effectively treated with CAR T therapy that targets the B-cell maturation antigen (BCMA). Researchers are also investigating combination therapies, which couple CAR T therapy with additional medications, including checkpoint inhibitors, to enhance results [ 49 ].

DEVELOPMENT OF mRNA VACCINE

The development of mRNA vaccines has been a significant milestone in the fight against COVID-19 [ 50 ]. The Pfizer-BioNTech and Moderna mRNA vaccines have demonstrated remarkable efficacy and safety profiles in preventing COVID-19 infection and its complications [ 7 , 51 , 52 ]. The mRNA technology used in these vaccines has several advantages over traditional vaccine production methods, including faster development and manufacturing times, lower production costs, and greater flexibility in responding to emerging viral variants [ 53 , 54 ].

Clinical trials of the Pfizer-BioNTech and Moderna vaccines have shown high levels of protection against COVID-19. A study by Polack et al. [ 55 ] found that the Pfizer-BioNTech vaccine had an efficacy rate of 95% in preventing COVID-19 infection, while a study by Baden et al. [ 56 ] reported a similar efficacy rate of 94.1% for the Moderna vaccine. Additionally, real-world data has confirmed the high effectiveness of mRNA vaccines in preventing severe disease, hospitalization, and death caused by COVID-19 [ 57 ].

Another company that has been working on developing mRNA vaccines for COVID-19 is Novavax [ 58 ]. The company's vaccine candidate combines mRNA technology with nanoparticles to enhance the body's immune response [ 59 ]. In clinical trials, the vaccine demonstrated efficacy against both the original strain of COVID-19 and certain variants of the virus [ 60 ].

Companies such as Moderna and BioNTech are now exploring the potential of mRNA vaccines for a wide range of illnesses, including cancer and influenza [ 61 ]. The development of mRNA vaccines also holds promise for creating rapid responses to new and emerging infectious diseases, as the technology allows for quick adaptation to new viral strains [ 7 , 54 , 61 , 62 ].

Overall, the development of mRNA vaccines for COVID-19 represents a significant breakthrough in vaccine technology, with potential implications for future disease prevention and treatment [ 53 ].

ADVANCES IN 3D PRINTING FOR MEDICAL APPLICATIONS

The development of complex anatomical models, prostheses, implants, and drug delivery systems has been made possible by advances in 3D printing technology [ 8 ]. 3D printing has enabled the development of custom-made implants, reducing the need for invasive surgeries and improving patient outcomes. The successful implantation of 3D printed titanium-mesh implants for the repair of bone deformities was described in a study by Ma et al. [ 63 ]. Anatomical models that have been 3D printed have been proven to be useful for planning surgeries and advancing medical knowledge. The use of 3D printed models for surgical planning in complicated craniofacial patients was reported in a study by Charbe et al. [ 64 ]. The development of 3D printing technology has the potential to revolutionise the medical industry by enabling more individualized and efficient patient care [ 65 ].

TELEMEDICINE TO PROVIDE REMOTE CARE

Over the past few years, telemedicine – the use of technology to deliver medical treatments remotely – has grown in popularity, especially during the COVID-19 pandemic [ 66 ]. Telemedicine allows health care providers to offer virtual consultations, monitor patients remotely, and provide access to medical services in areas with limited health care resources [ 67 ]. Telemedicine was linked to better health care access and outcomes for patients with cardiovascular disease during the COVID-19 pandemic [ 9 ]. Telemedicine also has the potential to lower medical expenses and raise patient satisfaction. High levels of patient satisfaction with teleconsultations for dermatology services were observed in a study by Nicholson et al. [ 68 ]. Telemedicine use is anticipated to increase over the next few years, which might have a significant impact on how health care is delivered in the future [ 9 , 69 ].

VERTUAL REALITY IN MEDICAL TRAINING

Medical students can practice and hone their skills in a safe and controlled environment with the help of virtual reality (VR), which has grown in popularity in recent years [ 70 ]. Students can practice medical procedures and scenarios using VR technology, which helps them become more adept at diagnosing and treating patients [ 71 ]. According to a recent study by Yiasemidou et al. [ 72 ], medical students' performance and confidence improved when VR was used for surgical instruction. Moreover, using VR technology can replace animal or cadaveric models in training for less common medical operations. The effective use of VR technology in training for transesophageal echocardiography was described in a study by Arango et al. [ 73 ]. The use of VR in medical education has the potential to raise the standard of medical instruction and increase patient safety [ 74 ].

DEVELOPMENT OF WEARABLE DEVICES FOR HEALTH MONITORING

The development of wearable health monitoring technology has completely revolutionised how people track and manage their health [ 75 ]. Individuals can receive real-time feedback on their health state by using wearable devices, such as fitness trackers and smartwatches, which can gather data on physical activity, heart rate, blood oxygen saturation, sleep habits, and other health markers [ 76 ]. These devices capture data that can be analysed to find trends and patterns that can provide important information about a person's general health and well-being [ 77 , 78 ]. According to research by Patel et al. [ 79 ], adult users of wearable technology had increases in physical activity and weight loss. Moreover, wearable technology can be used to monitor patients with chronic illnesses remotely, enabling health care professionals to monitor patient progress and take appropriate action as needed. According to a study by Gautam et al. [ 80 ], wearable devices are useful for remotely monitoring patients with heart failure [ 80 , 81 ]. By encouraging early disease identification and prevention, wearable health monitoring technology has the potential to enhance health outcomes and save health care costs [ 78 ].

CONCLUSIONS

In conclusion, the most recent developments in medical science have the potential to completely revolutionise the way health care is provided and greatly enhance patient outcomes. With the advent of modern technologies like telemedicine, gene editing, and AI, doctors are now able to detect and treat illnesses more precisely and effectively. Moreover, the application of nanotechnology, 3D printing, and regenerative medicine is bringing about ground-breaking treatments for previously incurable diseases. The advances being made in medical science are genuinely astonishing and give hope for a healthier future, even though there are still obstacles to be addressed. In the years to come, we may anticipate even more interesting advances with ongoing innovation and investment.

Acknowledgements

We would like to acknowledge the support of Prof Xuerui Tan, from Shantou University Medical College. Additionally, we extend our gratitude to the clinical research center team at the first affiliated Hospital of Shantou University Medical College.

Funding: This work was funded by the Provincial Science and Technology Special Fund of Guangdong, China (2021123071-1).

Authorship contributions: GM and WW conceived the research idea. GM drafted the manuscript. CT and XX, collected information and reviewed the manuscript. WW, acting as the principal investigator, assisted in revising the manuscript. The final version of the manuscript was critically reviewed and approved by all authors.

Disclosure of interest: The authors have completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

• Open access
• Published: 29 March 2023

Mapping ethical issues in the use of smart home health technologies to care for older persons: a systematic review

• Nadine Andrea Felber   ORCID: orcid.org/0000-0001-8207-2996 1 ,
• Yi Jiao (Angelina) Tian   ORCID: orcid.org/0000-0003-2969-9655 1 ,
• Félix Pageau   ORCID: orcid.org/0000-0002-4249-7399 2 ,
• Bernice Simone Elger   ORCID: orcid.org/0000-0003-0857-0510 1 &
• Tenzin Wangmo 1  

BMC Medical Ethics volume  24 , Article number:  24 ( 2023 ) Cite this article

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The worldwide increase in older persons demands technological solutions to combat the shortage of caregiving and to enable aging in place. Smart home health technologies (SHHTs) are promoted and implemented as a possible solution from an economic and practical perspective. However, ethical considerations are equally important and need to be investigated.

We conducted a systematic review according to the PRISMA guidelines to investigate if and how ethical questions are discussed in the field of SHHTs in caregiving for older persons.

156 peer-reviewed articles published in English, German and French were retrieved and analyzed across 10 electronic databases. Using narrative analysis, 7 ethical categories were mapped: privacy, autonomy, responsibility, human vs. artificial interactions, trust, ageism and stigma, and other concerns.

The findings of our systematic review show the (lack of) ethical consideration when it comes to the development and implementation of SHHTs for older persons. Our analysis is useful to promote careful ethical consideration when carrying out technology development, research and deployment to care for older persons.

Registration

We registered our systematic review in the PROSPERO network under CRD42021248543.

Peer Review reports

Introduction/background

Significant advancements in medicine, public health and technology are allowing the world population to grow increasingly older adding to the steady rise in the proportion of senior citizens (aged over 65) [ 1 ]. Because of this growth in the aging population, the demand for and financial costs of caring for older adults are both rising [ 2 ]. That older persons generally wish to age in place and receive healthcare at home [ 2 ] may mean accepting risks such as falling, a risk that increases with frailty [ 3 ]. However, many prefer accepting these risks rather than moving into long term care facilities [ 4 , 5 , 6 ].

A solution to this multi-facetted problem of ageing safely at home and receiving appropriate care, while keeping costs at bay may be the use of smart home health technologies (SHHTs). A smart home is defined by Demiris and colleagues as “ residence wired with technology features that monitor the well-being and activities of their residents to improve overall quality of life, increase independence and prevent emergencies” [ 7 ]. SHHTs then, represent a certain type of smart home technology, which include non-invasive, unobtrusive, interoperable and possibly wearable technologies that use a concept called the Internet-of-Things (IoT) [ 8 ]. These technologies could thereby remotely monitor the older resident and register any abnormal deviations in the daily habits and vital signs while sending alerts to their formal and informal caregivers when necessary. These SHHTs could permit older people (and their caregivers) to receive the necessary medical support and attention at their convenience and will, thereby allowing them to continue living independently in their home environment.

All of these functions offer benefits to older persons wishing to age at home. While focusing on practical advantages is important, an equally important question to ask is how ethical these technologies are when used in the care of older persons. Principles of biomedical ethics, such as autonomy, justice [ 9 ], privacy [ 10 ], and responsibility [ 11 ] should not only be respected by medical professionals, but by technology developers and build-into the technologies as well.

The goal of our systematic review is therefore to investigate whether and which ethical concerns are discussed in the pertinent theoretical and empirical research on SHHTs for older persons between 2000 and 2020. Different from previous literature reviews [ 12 , 13 , 14 ],, which only explored practical aspects, we explicitly examined if and how researchers treated the ethical aspects of SHHTs in their studies, adding an important, yet often overlooked aspect to the systematic literature. Moreover, we present how and which ethical concerns are discussed in the theoretical literature and which ones in empirical literature, to shed light on possible gaps regarding which and how different ethical concerns are developed. Identifying these gaps is the first important step to eventually connecting bioethical considerations to the real world, adapting policies, guidelines and technologies itself [ 15 ]. Thus, our systematic review is the first one to do so in the context of ethical issues in SHHTs used for caregiving for older persons.

Search strategy

With the guidance of an information specialist from the University of Basel, our team developed a search strategy according to the PICO principle: Population 1 (Older adults), Population 2 (Caregivers), Intervention (Smart home health technologies), and Context (Home). The outcome of ethics was intentionally omitted as we wanted to capture all relevant studies without narrowing concerns that we would classify as “ethical”. Within each category, synonyms and spelling variations for the keywords were used to include all relevant studies. We then adapted the search string by using database-specific thesaurus terms in all ten searched electronic databases: EMBASE, Medline, PsycINFO, CINAHL, SocIndex, SCOPUS, IEEE, Web of Science, Philpapers, and Philosophers Index. We limited the search to peer-reviewed papers published between January 1st, 2000 and December 31st, 2020, written in the English, French, and German languages. This time frame allowed us to map the evolution to SHHTs as a new field.

The inclusion criteria were the following: (1) The article must be an empirical or theoretical original research contribution. Hence, book chapters, conference proceedings, newspaper articles, commentary, dissertations, and thesis were excluded. Also excluded were other systematic reviews since their inclusion would duplicate findings from our individual studies. (2) When the included study was empirical, the study’s population of interest must be older persons over 65 years of age, and/or professional or informal caregivers who provide care to older persons. Informal caregivers include anyone in the community who provided support without financial compensation. Professional caregivers include nurses and related professions who receive financial compensation for their caregiving services. (3) The included study must investigate SHHTs and their use in the older persons’ place of dwelling.

First, we carried out the systematic search across databases and removed all duplicates through EndNote (see supplementary Table  1 in appendix part 1 for a list of all included articles). One member of the research team screened all titles manually and excluded irrelevant papers. Then, two authors screened the abstracts and excluded irrelevant papers, and any disagreements were solved by a third author. She then also combined all included articles and removed further duplicates.

PRISMA 2020 Flowchart

Final inclusion and data extraction

All included articles were searched and retrieved online (and excluded if full text was not available). Three co-authors then started data extraction, where several papers were excluded due to irrelevant content. To code the extracted data, a template was developed, which was tested in a first round of data extraction and then used in Microsoft Excel during the remaining extraction process. Study demographics and ethical considerations were recorded. Each extracting author was responsible for a portion of articles. If uncertainties or disputes occurred, they were solved by discussion. To ensure that our data extraction was not biased, 10% of the articles were reviewed independently. Upon comparing data extracted of those 10% of our overall sample, we found that items extracted reached 80% consistency.

Data synthesis

The extracted datasets were combined and ethical discussions encountered in the publications were analyzed using narrative synthesis [ 16 ]. During this stage, the authors discussed the data and recognized seven first-order ethical categories. Information within these categories were further analyzed to form sub-categories that describe and/or add further information to the key ethical category.

Nature of included articles

Our search initially identified 10,924 papers in ten databases. After the duplicates were removed, 9067 papers remained whose titles were screened resulting in exclusion of 5215 papers (Fig.  1 ). The examination of remaining 3845 abstracts of articles led to the inclusion of 374 papers for full-texts for retrieval. As we were unable to find 20 papers after several attempts, the remaining 354 full-texts were included for full-text review. In this full-text review phase, we further excluded 198 full-texts with reasons (such as technologies employed in hospitals, or technologies unrelated to health). Ultimately, this systematic review included 144 empirical and 12 theoretical papers specifying normative considerations of SHHTs in the context of caregiving for older persons.

Almost all publications (154 out of 156) were written in English, and over 67% [ 105 ] were published between 2014 and 2020. About a quarter (26%; 41 papers) were published between 2007 and 2013 and only 7% (10 articles) were from 2000 to 2006. Apart from the 12 theoretical papers, the methodology used in the 144 empirical papers included the following: 42 articles (29%) used a mixed-methods approach, 39 (27%) experimental, 38 (26%) qualitative, 15 (10%) quantitative, and the remaining were of an observational, ethnographical, case-study, or iterative testing nature.

The functions of SHHTs tested or studied in the included empirical papers were categorized as such: 29 articles (20.14%) were solely involved with (a) physiological and functioning monitoring technologies, 16 (11.11%) solely with (b) safety/security monitoring and assistance functions, 23 (15.97%) solely promoted (c) social interactions, and 9 (6.25%) solely for (d) cognitive and sensory assistance. However, 46 articles (29%) also involved technologies that fulfilled more than one of the categorized functions. The specific types of SHHTs included in this review comprised: intelligent homes (71 articles, 49.3%); assistive autonomous robots (49 articles, 34.03%); virtual/augmented/mixed reality (7, 4.4%); and AI-enabled health smart apps and wearables (4 articles, 1.39%). Likewise, the remaining 20 articles (12.8.8%) involved either multiple technologies or those that did not fall into any of the above categories.

Ethical considerations

Of the 156 papers included, 55 did not mention any ethical considerations (See supplementary Table  1 in appendix part 1). Among the 101 papers that noted one or more ethical considerations, we grouped them into 7 main categories (1) privacy, (2) human vs. artificial relationships, (3) autonomy, (4) responsibility, (5) social stigma and ageism, (6) trust, and (7) other normative issues (see Table  1 ). Each of these categories consists of various sub-categories that provided more information on how smart home health technologies (possibly) affected or interacted with the older persons or caregivers in the context of caregiving (Table  2 ). Each of the seven ethical considerations are explained in depth in the following paragraphs.

This key category was cited across 58 articles. In theoretical articles, privacy was one of the most often discussed ethical consideration, as 9 out of 12 mentioned privacy related concerns. Among the 58 articles, four sub-issues within privacy were discussed.

(A)The awareness of privacy was reported as varying according to the type of SHHT end-user. Whereas some end-users were more aware or privacy in relation to SHHTs, others denoted little or a total lack of consideration, while some had differing levels of concerns for privacy that changed as it is weighed against other values, such as access to healthcare [ 17 ] or feeling of safety [ 18 ]. Both caregivers and researchers often took privacy concerns into account [ 19 , 20 , 21 ], while older persons themselves did not share the same degree of fears or concerns [ 22 , 23 , 24 ]. Older persons in fact were less concerned about privacy than costs and usability [ 23 ]. Furthermore, they were willing to trade privacy for safety and the ability to live at home. Nevertheless, several papers acknowledged that privacy is an individualized value, whereby its significance depends on both the person and their context, thus their preferences cannot be generalized [ 25 , 26 , 27 , 28 ]. Lastly, there were also some papers that explicitly stated that there were no privacy concerns found by the participants, or that participants found it useful to have monitoring without mentioning privacy as a barrier [ 29 , 30 , 31 ].

The second prevalent sub-issue within privacy was (B) privacy by choice. Both older persons and their caregivers expressed a preference for having a choice in technology used, in what data is collected, and where technology should or should not be to installed [ 32 , 33 ]. For example, some spaces were perceived as more private and thus monitoring felt more intrusive [ 34 , 35 , 36 ]. Formal caregivers were concerned about monitoring technologies being used as a recording device for their work [ 37 , 38 ]. Furthermore, older persons were often worried about cameras [ 39 , 40 ] and “eyes watching”, even if no cameras were involved [ 41 , 42 , 43 ].

The third privacy concern was (C) risk and regulation of privacy, which included discussions surrounding dissemination of data or active data theft [ 44 , 45 , 46 , 47 ], as well as change in behavior or relationships due to interaction with technology [ 48 , 49 ]. Researchers were aware of both legal and design-contextual measures that must be observed in order to ensure that these risks were minimized [ 45 , 50 , 51 ].

The final sub-issue that we categorized was (D) privacy in the case of cognitive impairment. This included disagreements if cognitive impairment warrants more intrusive measures or if privacy should be protected for everyone in the same way [ 52 , 53 ].

Human versus artificial relationships

54 articles in our review contained data pertinent to trade-offs between human and artificial caregiving. Firstly, (A) there was a general fear that robots would replace humans in providing care for older persons [ 28 , 54 , 55 , 56 ], along with related concerns such as losing jobs [ 40 , 57 ], disadvantages with substituting real interpersonal contact [ 17 , 46 ], and thus increasing the negative effects associated with social isolation [ 41 , 58 ].

Many papers also emphasized (B) the importance of human caregiving, underlining the necessity of human touch [ 26 , 47 , 50 , 59 ] believing that technology should and could not replace humans in connections [ 17 ], love [ 33 ], relationships [ 60 ], and care through attention to subtle signs of health decline in every in-person visit [ 57 ]. Older persons also preferred human contact over machines and had guarded reactions to purely virtual relationships[ 31 , 61 , 62 ]. The use of technology was seen to dehumanize care, as care should be inherently human-oriented [ 27 , 48 ].

There was data alluding to (C) the positive reactions to technologies performing caregiving tasks and possibly forming attachments with the technology[ 47 , 49 , 58 ]. Furthermore, some papers cited participants reacting positively to robots replacing human care, where the concept of “good care” could be redefined [ 63 , 64 , 65 , 66 ]. Solely theoretical papers also identified possible benefits of tech for socialization and relationship building [ 67 , 68 ].

Finally, many articles raised the idea of (D) collaboration between machine and human to provide caregiving to older persons [ 69 ]. These studies highlighted the possible harms if such collaboration was not achieved, such as informal caregivers withdrawing from care responsibilities [ 70 ] or the reinforcement of oppressive care relations [ 71 ]. Interestingly, opinions varied on whether the caregiving technology, such as a robot should have “life-like” appearance, voices, and emotional expressions, while recognizing the current technological limits in actually providing those features to a satisfactory level [ 46 ]. For example, some users preferred for the robot to communicate with voice commands, while others wanted to further customize this function with specific requests on the types of voices generated [ 65 , 72 ].

40 papers mentioned autonomy of the older person with respect to the use of SHHTs. The first sub-theme categorized was in relation to (A) control, which encompassed positive aspects like (possible) empowerment through technology [ 25 , 26 , 73 , 74 ] and negative aspects such as the possibility of technology taking control over the older person, thus increasing dependence [ 55 , 75 ] or decreasing freedom of decision making [ 48 ]. Several studies reported the wishes of older persons to be in control when using the technology (e.g. technology should be easily switched off or on) and be in control of its potential, meaning the extend of data collected or transferred, for example [ 17 , 30 , 70 , 76 ]. Furthermore, they should have the option to not use technology in spaces where they do not wish to, e.g., public spaces [ 35 ]. The issue of increased dependency was discussed as a loss or rather, fear of the loss of autonomy due to greater reliance on technology as well as the fear of being monitored all the time [ 28 , 48 ]. In addition, using technology was deemed to make older persons more dependent and to increase isolation [ 77 ].

The second sub-category within autonomy highlighted the need for the technology to (B) protect the autonomy and dignity of its older end-users, which also included the unethical practice of deception (e.g.[ 46 , 49 , 54 , 78 ], infantilization [ 31 , 60 ], or paternalism [ 17 , 27 , 57 ], as a way to disrespect older persons’ dignity and autonomy [ 79 , 80 , 81 ]. Also reported was that these users may accept technology to avoid being a burden on others, thus underscoring the value of technology to enhance functional autonomy, understood here as independent functioning [ 52 , 82 , 83 ]. Other studies mentioned this kind of trade-off between autonomy and other values or interests as well. For example, between respecting the autonomy of the older persons versus nudging them towards certain behavior (perceived as beneficial for them) through the help of technology [ 32 ], or between autonomy and safety [ 24 ].

Two sub-issues within autonomy primarily discussed in the theoretical publications were (C) relational autonomy [ 27 , 41 , 49 , 58 ] and (D) explanations on why autonomy should actually be preserved. The former emphasized the fact that older persons do not and should not live isolated lives and that there should be respect and promotion of their relationships with family members, friends, caregivers, and the community as a whole [ 27 , 47 ]. The latter described the benefits of respecting autonomy, such as increased happiness and well-being [ 65 , 67 ] or a sense of purpose [ 84 ], and thus favoring the promotion of autonomy and choice also from a normative perspective.

Responsibility

This theme included data across 25 articles that mentioned concerns such as the effect of using technologies on the current responsibilities of caregivers and older persons themselves. Specifically, the papers discussed (A) the downsides of assistive home technology on responsibility. That is, the use of technology conflicted with moral ideas around responsibility [ 58 ], especially for caregivers [ 57 , 59 ]. Its use also raised more practical concerns, such as the fear of shifting the responsibility onto the technology and thus, diminishing vigilance and/or care. Related to this thought was also a fear of increased responsibility on both older persons [ 60 ] and their caregivers, who were worried about extra work time was needed to integrate technology into their work, learn its functions, analyze data, and respond to potentially higher frequencies of alerts [ 18 , 35 , 36 , 53 , 85 ].

Additionally, studies reported (B) continuous negotiation between (formal) caregivers’ (professional) responsibilities of care and the opportunities that smart technologies could provide [ 26 , 47 , 55 , 70 , 82 ]. For example, increased need for cooperation between informal and formal caregivers due to technology was foreseen [ 81 ] and fear expressed that over-reliance on female caregivers was exacerbated [ 71 ]. Nevertheless, the use of smart home health technologies was often seen to (C) reduce the burden of care, where caregivers could direct their attention and time to the most-needed situations and better align the responsibilities of care [ 5 , 18 , 49 , 74 , 80 , 81 ]. This shift of burden onto a technology was also reported by older persons as freeing [ 48 ].

Ageism and stigma

24 articles discussed ageism and stigma, which included discussions about fear of (A) being stigmatized by others with the use of SHHTs [ 73 , 86 ]. Older persons thought acceptance of such technologies also alluded to an admission of failure [ 82 ], or being perceived by others as frail, old, forgetful [ 77 , 87 ], or even stupid [ 26 , 33 , 88 ]. This resulted in them expressing ageist views stating that they did not need the technology “yet” [ 84 , 89 ]. Some papers reported the belief that the presence of robots was disrespectful for older people [ 52 , 85 , 90 ] and technologies do little to alleviate frustration and the impression of “being stupid” that older persons may have when they are faced with the complexities of the healthcare system [ 73 ]. Furthermore, older persons in a few studies did express unfamiliarity with learning new technologies in old age [ 42 , 66 , 91 ], coupled with fears of falling behind and not keeping up with their development, and feeling pressured to use technology [ 62 , 89 ].

Within ageism and stigma, (B) social influence was deemed to cause older persons to believe that the longer they have been using technology, the more their loved ones want them to use it as well, creating a sort of reinforcing loop [ 27 ]. Other social points were related to self-esteem, meaning that older persons needed to reach a certain threshold first to publicly admit that they need technology [ 85 ], or doubts by caregivers if they were able to use the devices [ 36 ]. This possibly led older persons to prefer unobtrusive technology and those that could not be noticed by visitors [ 22 , 55 , 88 ].

Lastly, (C) two theoretical articles raised concerns in regard to technology exacerbating stigmatization of women and migrants in caregiving. Both Parks [ 47 ] and Roberts & Mort [ 71 ] suggested that caregiving technology which does not question the underlying expectation that women give care to their relatives will worsen such gendered expectations in caregiving.

We identified 18 articles that mentioned some aspect of trust. For both older persons and caregivers, there was often (A) a general mistrust with technologies compared with existing human caregiving [ 33 , 42 ]. Therefore, caregivers became proxies and were relied on to “understand it” and continue providing care [ 48 ]. For caregivers the lack of trust was associated with the use of technologies, for example, leaving older persons alone with technology [ 81 ], worrying that older persons would not trust the technology [ 29 , 32 ] or that it could change their professional role [ 23 ]. One paper even reported that using technology meant caregivers themselves are not trusted [ 92 ]. Surprisingly, some studies found that older persons had no problem trusting technology, even considering it safer and more reliable than humans [ 58 , 70 ].

The second sub-theme concerned (B) characteristics promoting trust. That is, the degree of automation [ 30 ](, the involvement of trusted humans in design and use [ 34 , 93 ], perceived usefulness of the technology and spent time with the technology all influenced trust [ 59 , 72 , 94 ]. For robots specifically, they were trusted more than virtual agents, such as Alexa [ 60 , 65 ]. Taking this step further, studies discovered that robots with a higher degree of automation or a lower degree in anthropomorphism level increased trust [ 30 ].

There were several miscellaneous considerations not fitting the ones already mentioned above, and we categorized them as follows. Firstly, two theoretical articles mentioned (A) considerations related to research. Ho, [ 27 ] pointed out that empirical evidence of the usefulness of SHHTs is lacking, which therefore may make them less relevant as a possible solution for aging in place. Palm et al. (2013) suggested that, if research would consider the fact that many costs of caregiving are hidden because of non-paid informal caregivers, the actual economic benefits of SHHTs are unknown. Lastly, two articles alluded to (B) psychological phenomena related to the use of SHHTs. Pirhonen et al., [ 58 ] suggested that robots can promote the ethical value of well-being through the promotion of feelings of hope. The other phenomenon was feeling of blame and fear associated with the adoption of the technology, as caregivers may be pushed to use SHHTs in order to not be blamed for failing to use technology [ 18 ]. This then also nudged caregivers to think that using SHHTs cannot do any harm, so it is better to use it than not use it.

Our systematic review investigated if and how ethical considerations appear in the current research on SHHTs in the context of caregiving for older persons. As we included both empirical and theoretical works of literature, our review is more comprehensive that existing systematic reviews (e.g.[ 12 , 13 , 14 ], that have either only explored the empirical side of the research and neglected to study ethical concerns. Our review offers an informative and useful insights on dominant ethical issues related to caregiving, such as autonomy and trust [ 95 , 96 ]. At the same time, the study findings brings forth less known ethical concerns that arise when using technologies in the caregiving context, such as responsibility [ 97 ] and ageism and stigma.

The first key finding of our systematic review is the silence on ethics in SHHTs research for caregiving purposes. Over a third of the reviewed publications did not mention any ethical concern. One possible explanation is related to scarcity [ 98 ]. In the context of research in caregiving for older persons, “scarcity” can be understood in a variety of ways: one way is to see the available space for ethical principles in medical technology research as scarce. For example, according to Einav & Ranzani [ 99 ] “Medical technology itself is not required to be ethical; the ethics of medical technology revolves around when, how and on whom each technology is used” (p.1612). Determining the answers to these questions is done empirically, by providing proof of benefit of the technology, ongoing reporting on (possibly harmful) long term effects, and so on [ 99 ]. Given that publication space in journal is limited to a certain amount of text, the available space that ethical considerations can take up is scarce. Therefore, adding deliberations about the unearthed values or issues in our systematic review, like trust, responsibility or ageism, may simply not fit in the space available in research publications. This may also be the reason why the values of beneficence and non-maleficence were not found through our narrative analysis. While both values are considered crucial in biomedical ethics [ 9 ], the empirically measured benefits may be considered enough by the authors to demonstrate beneficence (and non-maleficence), leading them to not mention the ethical values explicitly again in their publications.

Another interpretation is the scarcity of time, and the felt pressure to “solve” the problem of limited resources in caregiving [ 2 ]. Researchers might be therefore more inclined to focus on the empirical data showing benefits, rather than to engage in elaborations on ethical issues that arise with those benefits. Lastly, as researchers have to compete for limited funding [ 100 ] and given that technological research receives more funding than biomedical ethics [ 101 ], it is likely that the numbers of publications mentioning purely empirical studies exceeds those publications that solely mention the ethical issues (as our theoretical papers did) or that combine empirical and ethical parts. Further research needs to investigate these hypotheses further.

It is not surprising that privacy was the most discussed ethical issue in relation to SHHTs in caregiving. The topic of privacy, especially in relation to monitoring technologies and/or health, has been widely discussed (see for example [ 102 , 103 , 104 ]. A particularly interesting finding within this ethical concern was related to privacy and cognitive impairment. While discussions around autonomy and cognitive impairment are popular in bioethical research (see e.g. [ 105 , 106 ], privacy, on the other hand, has recently gained more attention for both researchers and designers [ 107 ]. The relation in the reviewed studies between cognitive impairment and privacy seemed to be reversely correlated –intrusions into the privacy of older persons with cognitive impairments were deemed as more justified [ 35 , 53 ], which necessarily does not mean that its ethical, but a practical fact that such intrusions become possible or necessary in the given context. A possible explanation lies in the connectedness of autonomy and privacy, in the sense that autonomy is needed to consent for any sort of intrusions [ 108 ].

Surprisingly, more research papers mentioned the topic of human vs. artificial relationships as an ethical concern than autonomy. Autonomy is often the most discussed ethics topic when it comes to use of technology [ 96 ]. However, fears associated with technology replacing human care has recently gained traction [ 109 , 110 , 111 ].The significance of this theme is likely due to the fact that caregiving for older persons has been (and is) a very human-centric activity [ 112 ]. As mentioned before, the persons willing and able to do this labor (both paid and unpaid caregiver) are limited and their pool is shrinking [ 113 ]. The idea of technology possibly filling this gap is not new [ 114 ], but is also clearly causing wariness among both older persons and caregivers, as we have discovered [ 56 , 61 ]. Frequently mentioned was the fear of care being replaced by technology. This finding was to be expected, as nursing is not the only profession where introduction of technology caused fears of job loss [ 115 ]. Within this ethical concern, the importance of human touch and human interaction was underlined [ 110 , 111 ]. Human touch is an important asset for caregivers when they care for older patients, particularly those with dementia, as it is one of the few ways to establish connection and to calm the patient with dementia [ 116 ]. Similarly, human touch and face-to-face interactions are mentioned as a critical aspect of caregiving in general, both for the care recipient and the caregiver [ 117 , 118 ]. While caregivers see the aspect of touching and interacting with older care recipients as a way to make their actions more meaningful and healing [ 90 , 117 ], for care recipients being touched, talked and listened to is part of feeling respected and experiencing dignity [ 118 , 119 ]. Introducing technology into the caregiving profession may therefore quickly elicit associations with cold and lifeless objects [ 59 ]. Future developments, both in the design of the technologies themselves and their implementation in caregiving will require critical discussion among concerned stakeholders and careful decision on how and to what extent the human touch and human care must be preserved.

A unique ethical concern that we have not seen in previous research [ 120 , 121 ] is responsibility, and remarkable within this concern was SHHTs’ negative impact on it. As previously mentioned, the human being and human interaction are seen as central to caregiving [ 117 , 118 ]. This can possibly be extended to concepts exclusively attributable to humans, such as the concept of moral responsibility [ 122 ]. Shifting caregiving tasks onto a technological device, which, by being a device and not a human carer, cannot be morally responsible in the same way as a human being can [ 123 ], may introduce a sense of void that caregivers are reluctant to create. Studies have shown that a mismatch in professional and personal values in nursing causes emotional discomfort and stress [ 124 ], therefore the shift in the professional environment caused by SHHTs is likely to be met with aversion. Additionally, the negative impact of SHHTs on caregiving responsibility was also tied to practical concerns, like not having enough time to learn how to use the technology by the caregivers [ 35 ], or needing to have access to and checking the older person’s health data [ 36 ]. Such concerns point to the possibility that SHHTs can create unforeseen tasks, which could turn into true burdens, instead of alleviating caregivers. Indeed, there are indications that the increase in information about the older person through monitoring technologies causes stress for both caregivers and older persons, as the former feel pressure to look at the available data, while the latter prefer to hide unfavorable information to not seem burdensome for their caregivers [ 125 ]. Another consequence of SHHTs that emerged as a sub-category was the renegotiation of responsibilities among the different stakeholders. In the field of (assistive) technology, this renegotiation is an ongoing process with efforts to make technology and its developers more accountable, through new policies and regulations [ 126 ]. In the realm of assistive technology in healthcare, these negotiations focus on high-risk cases and emergencies [ 127 ]. Who is responsible for the death of a person if the assistive technology failed to recognize an emergency, or to alert humans in time? Such issues around responsibility and legal liability are partially responsible for the slow uptake of technology in caregiving [ 128 ].

Another important but less discussed ethical concern was ageism and stigma. Ageist prejudices include being perceived as slow, useless, burdensome, and incompetent [ 129 ]. Fear of aging and becoming a burden to others is a fear many older persons have, as current social norms demand independence until death [ 130 ]. Furthermore, the general ubiquitous use of technology has possibly exacerbated the issue of ageism, as life became fast paced and more pressure is placed on aging persons to keep up [ 131 ]. While this would call for more attention to studying ageism in relation to technology, our findings indicate that, it does not unfortunately seem at the forefront of concerns that are prevalent in the literature (and thereby the society).

Related to ageism, is the wish of older persons to not be perceived as old and/or in the need of assistance (in the form of technology) explains the prevalent demand for unobtrusive technology. Obtrusiveness, in the context of SHHTs, is defined as “undesirably prominent and or/noticeable”, yet this definition should include the user’s perception and environment, and is thus not an objectively applicable definition [ 132 ]. Nevertheless, we can infer that by “unobtrusive”, users mean SHHTs that is not noticeable by them or, mostly importantly, by other persons to possibly reduce stigma associated with using a technology deemed to be for persons with certain limitations. Further research will have to confirm if unobtrusive technology actually reduces stigma and/or fosters acceptance of such SHHTs in caregiving.

Lastly, the sub-theme of stigmatization of women and immigrants in caregiving and possibly exacerbating their caregiving burden through technology was only discovered in two theoretical publications [ 47 , 71 ]. While it is well known that caregiving burden mostly falls upon women [ 133 , 134 ], many of them with a migration background when it comes to live-in caregivers [ 135 , 136 ]. It is surprising that we found no redistribution of burden of care with technology. This is likely due to the fact that caregiving – be it technologically assisted or not – remains perceived as a more feminine and, unfortunately, low status profession [ 137 ]. The development of technology, however, are still mostly associated with masculinity This tension between the innovators and actual users of technology can lead to the exacerbation of stigma for female and migrant caregivers, as the human bias is conserved by the technology, instead of disrupted through it [ 137 ].

Finally, trust was an expected ethical concern, given that it is a widely discussed topic in relation to technology (see for example, [ 123 , 138 ] and also in the context of nursing [ 95 , 139 ]. Older persons were trusting caregivers to understand SHHTs [ 48 ], while caregivers feared that older persons would not trust the used technology, even though said persons did not express such concerns [ 32 ]. A possibility to mitigate such misunderstandings and put both caregivers and care recipients on an equal understanding of the technology are education tools [ 140 ]. Another surprising finding was that some older persons were inclined to trust SHHTs even more than human caregivers, as they were seen as more reliable [ 70 ]. This trust in technology was increased when a physical robot instead of an only virtual agent was involved [ 60 , 65 ]. Studies in the realm of embodiment of virtual agents and robots suggest that the presence of a body or face promotes human-like interactions with said agents [ 51 ]. Furthermore, our systematic review discovered other characteristics which promote trust in SHHTs, such as perceived usefulness [ 94 ] or time spent with the technology [ 59 ]. Another important aspect is the already existing trust in the person introducing the technology to the user [ 34 , 93 ]. In combining these characteristics in the design and implementation of SHHTs in caregiving, researchers and technology developers need to find creative mechanisms to facilitate trustworthiness and foster adoption of new technologies in caregiving.

Limitations

While we searched 10 databases for publications over a span of 20 years, we are aware that older or newer publications will have escaped our systematic review. Relevant new literature that we have found when writing our results have been incorporated in this manuscript. Furthermore, as we specifically refrained from using terms related to ethics in our search strings to also capture the instances of absence of ethical concerns, this choice may have led to missing a few articles as a consequence, especially in regards to theoretical publications. Lastly, due to lack of resources, we were unable to carry out independent data extraction for all included papers (N = 156) and chose to validate the quality of extracted data by using a random selection of 10% of the included sample. Since there was high agreement on extracted data, we are confident about the quality of our study findings.

SHHTs offer the possibility to mitigate the shortage of human caregiving resources and to enable older persons to age in place, being adequately supported by technology. However, this shift in caregiving comes with ethical challenges. If and how these ethical challenges are mentioned in the current research around SHHTs in caregiving for older persons was the goal of this systematic review. Through analyzing 156 articles, both empirical and theoretical, we discovered that, while over one third of articles did not mention any ethical concerns whatsoever, the other two thirds discussed a plethora of ethical issues. Specifically, we discovered the emergence of concerns with the use of technology in the care of older persons around the theme of human vs. artificial relationships, ageism and stigma, and responsibility. In short, our systematic review offers a comprehensive overview of the currently discussed ethical issues in the context of SHHTs in caregiving for older persons. However, scholars in the fields of gerontology, ethics, and technology working on such issues would be already (or should be) aware that ethical concerns will change with each developing technology and the population it is used for. For instance, with the rise of Artificial intelligence/Machine Learning, new intelligent or smart technologies will continue to mature with use and time. Thus, ethical value such as autonomy will require re-evaluation with this significant content development as well as deciding, if the person would/should be asked to re-consent or how should this decision making proceed should he or she have developed dementia. In sum, more critical work is necessary to prospectively act on ethical concerns that may arise with new and developing technologies that could be used in reducing caregiving burden now and in the future.

Data Availability

All data generated or analyzed during this systematic review are included in this published article and its appendices. Appendix part 1 contains all included articles and their characteristics. Appendix part 2 contains the search strategy and all search strings for all searched databases, as well as the PROSPERO registration number.

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We thank the information specialist of the University of Basel who advised us on our search strategy.

Open access funding provided by University of Basel. This study was supported financially by the Swiss National Science Foundation (SNF NRP-77 Digital Transformation, Grant Number 407740_187464/1) as part of the SmaRt homES, Older adUlts, and caRegivers: Facilitating social aCceptance and negotiating rEsponsibilities [RESOURCE] project. The funder neither took part in the writing process, nor does any part of the views expressed in the review belong to the funder.

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Felber, N.A., Tian, Y., Pageau, F. et al. Mapping ethical issues in the use of smart home health technologies to care for older persons: a systematic review. BMC Med Ethics 24 , 24 (2023). https://doi.org/10.1186/s12910-023-00898-w

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Touch can reduce pain, depression and anxiety, say researchers

More consensual touch helps ease or buffer against mental and physical complaints, meta-analysis shows

Whether it is a hug from a friend or the caress of a weighted blanket, the sensation of touch appears to bring benefits for the body and mind, researchers say.

The sense of touch is the first to develop in babies and is crucial in allowing us to experience the environment around us as well as communicate. Indeed, the loss of touch from others during the Covid pandemic hit many hard.

However, while myriad studies have suggested touch is beneficial for our health, few have attempted to draw the vast field of research together.

Now experts have done just that, revealing a simple message: touch helps.

Dr Helena Hartmann, a co-author of the research from University Hospital Essen , said: “More consensual touch events throughout our day can help alleviate or potentially buffer against mental and physical complaints.”

Published in the journal Nature Human Behaviour , the research encompassed 212 previously published studies and included a statistical analysis of 85 studies involving adults and 52 involving newborns.

Among the results, the team found touch was just as beneficial for mental health as physical health – a finding that held for adults and newborns – although touch had a bigger impact on some areas than others.

“Our work illustrates that touch interventions are best suited for reducing pain, depression and anxiety in adults and children as well as for increasing weight gain in newborns,” the researchers write.

The analysis revealed humans gained similar benefits in terms of their physical health when touched by other humans as by objects – such as social robots or weighted blankets.

Hartmann said that was a surprise. “This means we need to undertake more research on the potential of weighted blankets or social robots to improve people’s wellbeing, especially during contact-limiting situations like the recent Covid-19 pandemic,” she said.

The positive impact on mental health was larger for human touch than touch from objects – possibly, the team said, because it involved skin-to-skin contact.

Among other results, the team found touch was beneficial for both healthy and unwell people, although the impact was larger among the latter for mental health benefits.

The type of touch and its duration was not important, although greater frequency was associated with greater benefits in adults.

Further, touching the head was associated with greater health benefits than touching other parts of the body.

The team cautioned that some of the findings could be false positives, while it was not clear if they would hold across different cultures.

Dr Mariana von Mohr, from Royal Holloway, University of London, who was not involved in the work, said if future robots could more accurately replicate the texture and warmth of human skin, they may be able to provide comparable mental health benefits to human touch.

“[These properties are] important because our skin contains specialised sensors, known as C-tactile afferents, which are particularly receptive to gentle, caressing touch and temperature similar to that of human skin, factors that are also thought to facilitate emotional regulation,” she said.

Prof Katerina Fotopoulou, at University College London, said the research gave a bird’s-eye view of the benefits of touch interventions on health.

She cautioned that the work could not offer more specific conclusions, such as the particular types of touch that may be associated with specific health benefits.

Dr Susannah Walker, at Liverpool John Moores University, agreed, noting that many of the studies considered were small and included varied types of touch and different measures of their outcomes. “This means it is hard to draw firm conclusions about why they work,” she said.

Fotopoulou added that the research could fuel new work in the field, including how touch could be used alongside other treatments.

“It is a historical misfortune that we have prioritised talking over touch or other somatic therapies in the past couple of centuries. This review gives us the necessary emphasis and confidence to redress this balance with further, careful study on touch interventions,” she said.

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Collection  29 March 2022

2021 Top 25 Health Sciences Articles

We are pleased to share with you the 25 most downloaded  Nature Communications  articles* in health sciences published in 2021. (Please note we have a separate collection on the Top 25 COVID-19 papers .) Featuring authors from around the world, these papers highlight valuable research from an international community.

Browse all Top 25 subject area collections  here .

*Data obtained from SN Insights (based on Digital Science's Dimensions) and normalised to account for articles published later in the year.

Research highlights

Association of sleep duration in middle and old age with incidence of dementia

Sleep dysregulation has been linked to dementia, but it is unknown whether sleep duration earlier in life is associated with dementia risk. Here, the authors show higher dementia risk associated with short sleep duration (six hours or less) in a longitudinal study of middle and older age adults.

• Séverine Sabia
• Aurore Fayosse
• Archana Singh-Manoux

Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit

Aging is associated with an increased risk of chronic diseases and functional decline. Here, the authors investigate the fluctuations of physiological indices along aging trajectories and observed a characteristic decrease in the organism state recovery rate.

• Timothy V. Pyrkov
• Konstantin Avchaciov
• Peter O. Fedichev

Restoration of energy homeostasis by SIRT6 extends healthy lifespan

Aging is associated with increased frailty and disrupted energy homeostasis. Here, the authors show that SIRT6 overexpression extends the lifespan of male and female mice and demonstrate that SIRT6 optimizes energy homeostasis in old age, which delays frailty and preserves healthy aging.

• A. Roichman
• S. Elhanati
• H. Y. Cohen

Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates

No male contraceptive pills are currently available. Here, the authors use triptonide, a compound derived from a Chinese plant, to deform sperm so that they cannot move properly, thereby causing reversible infertility in male mice and monkeys.

• Zongliang Chang
• Weibing Qin

Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients

Nutritional modification including fasting has been shown to reduce cardiometabolic risk linked to western diet. Here the authors show implementation of fasting resulted in alterations to the intestinal microbiota, and circulating immune cells, improving blood pressure and body weight in patients with metabolic syndrome.

• András Maifeld
• Hendrik Bartolomaeus
• Sofia K. Forslund

Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice

The CNS has limited ability to regenerate following injury, Here, the authors show that a single injection of AAV-hyper-interleukin-6 in the sensory motor cortex results in corticospinal and raphe spinal tracts regeneration in the injured spinal cord as well as functional recovery in mice.

• Marco Leibinger
• Charlotte Zeitler
• Dietmar Fischer

Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface

During tumor progression, cancer cells contact different neighboring cell types, but it is unclear how these interactions affect cancer cell behavior. Here, the authors use spatially resolved transcriptomics and single-cell RNA-seq to study the role of cilia at the tumormicroenvironment interface.

• Miranda V. Hunter
• Reuben Moncada
• Richard M. White

Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination

Viruses expressing tumour antigens can prime and boost anti-tumour immunity but the efficiency of this approach depends on the capacity of the virus to infect the host. Here, the authors show that vaccination with oncolytic viruses co-administered with tumour antigenic peptides is as efficient as antigen-engineered oncolytic viruses.

• K. Geoffroy
• M.-C. Bourgeois-Daigneault

Detection and characterization of lung cancer using cell-free DNA fragmentomes

DNA from tumour cells can be detected in the blood of cancer patients. Here, the authors show that cell free DNA fragmentation patterns can identify lung cancer patients and when this information is further interrogated it can be used to predict lung cancer histological subtype.

• Dimitrios Mathios
• Jakob Sidenius Johansen
• Victor E. Velculescu

A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes

Community pharmacists are accessible healthcare providers with expertise in medication management. Here the authors show that a low-carbohydrate, low-energy diet implemented by community pharmacists reduced diabetes medication use and improved glucose control in people with type 2 diabetes.

• Cody Durrer
• Sean McKelvey
• Jonathan P. Little

A metabolome atlas of the aging mouse brain

Metabolites play an important role in physiology, yet the complexity of the metabolome and its interaction with disease and aging is poorly understood. Here the authors present a comprehensive atlas of the mouse brain metabolome and how it changes during aging.

• Oliver Fiehn

Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing

The tumor microenvironment (TME) has an important role in Head and Neck Squamous Cell Carcinoma (HNSCC) progression. Here, using single-cell RNA sequencing and multiplexed imaging, the authors report the cellular complexity of the TME in patients with HNSCC, exploring inflammatory status, stromal heterogeneity and immune checkpoint receptor-ligand interactions.

• Cornelius H. L. Kürten
• Aditi Kulkarni
• Robert L. Ferris

Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer

Comprehensive profiles of tumour and microenvironment are critical to understand heterogeneity in non-small cell lung cancer (NSCLC). Here, the authors profile 42 late-stage NSCLC patients with single-cell RNA-seq, revealing immune landscapes that are associated with cancer subtype or heterogeneity.

• Fengying Wu
• Caicun Zhou

Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy

Antibodies targeting OX40 or CD137, two T cell costimulatory receptors, have been shown to improve antitumor immunity. Here the authors design a phospholipid-derived nanoparticle to deliver OX40 or CD137 mRNA to T cells in vivo, improving efficacy of anti-OX40 and anti-CD137 antibody therapy in preclinical tumor models.

• Xinfu Zhang
• Yizhou Dong

Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome

Male sex is a risk factor for impaired glucose metabolism and type 2 diabetes. Here the authors identify that androgen modulates the gut microbiome, which drives insulin resistance and contributes to sexual dimorphism in glucose metabolism in mice.

• Weiqing Wang

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies

Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

• William S. Harris
• Nathan L. Tintle
• The Fatty Acids and Outcomes Research Consortium (FORCE)

Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes

Triple negative breast cancer can be divided into additional subtypes. Here, using omics analyses, the authors show that in the mesenchymal subtype expression of MHC-1 is repressed and that this can be restored by using drugs that target subunits of the epigenetic modifier PRC2.

• Brian D. Lehmann
• Antonio Colaprico
• X. Steven Chen

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition

Caloric restriction (CR) has been shown as an effective intervention to reduce tumorigenesis, but alternative less stringent dietary interventions have also been considered. Here, the authors show that in a murine model of breast cancer CR has a larger effect on preventing tumorigenesis and metastasis compared to periodic caloric cycling.

• Laura C. D. Pomatto-Watson
• Monica Bodogai
• Rafael de Cabo

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Immune checkpoint blockade has become standard care for patients with recurrent metastatic head and neck squamous cell carcinoma (HNSCC). Here the authors present the results of a non-randomized phase Ib/IIa trial, reporting safety and efficacy of neoadjuvant nivolumab monotherapy and nivolumab plus ipilimumab prior to standard-of-care surgery in patients with HNSCC. .

• Joris L. Vos
• Joris B. W. Elbers
• Charlotte L. Zuur

9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy

The molecular mechanisms of resistance to immune checkpoint therapy remain elusive. Here, the authors perform immunogenomic analysis of TCGA data and data from clinical trials for antiPD-1/PD-L1 therapy and highlight the association of 9p21 loss with a cold tumor microenvironment and resistance to therapy.

• Guangchun Han
• Guoliang Yang
• Linghua Wang

Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion

Several bacteria in the gut microbiota have been associated with colorectal cancer (CRC) but it is not completely clear whether they have a role in tumourigenesis. Here, the authors show enrichment of 12 bacterial taxa in two cohorts of CRC patients and that two Porphyromonas species accelerate CRC onset through butyrate secretion.

• Shintaro Okumura
• Yusuke Konishi

Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Follistatin promotes in type 2 diabetes (T2D) pathogenesis in model animals and is elevated in patients with T2D. Here the authors report that plasma follistatin associates with increased risk of incident T2D in two longitudinal cohorts, and show that follistatin regulates insulin-induced suppression lipolysis in cultured human adipocytes.

• Chuanyan Wu
• Yang De Marinis

Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation

Brain inflammation generally accelerates neurodegeneration but the mechanisms of this are not fully characterised. Here the authors show that PQBP1 in microglia is important for sensing extrinsic Tau 3 R/4 R proteins and triggers an innate immune response through cGAS and STING resulting in cognitive impairment.

• Hiroki Shiwaku
• Hitoshi Okazawa

Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice

Intervertebral disc degeneration is a leading cause of chronic back pain and disability. Here the authors show that long term treatment with senolytic compounds Dasatinib and Quercetin reduces disc senescence burden and ameliorates age-dependent degeneration in mice.

• Emanuel J. Novais
• Victoria A. Tran
• Makarand V. Risbud

DNA/RNA heteroduplex oligonucleotide technology for regulating lymphocytes in vivo

Using gene silencing to regulate lymphocyte function is a promising therapeutic approach for autommunity, inflammation and cancer. Here the authors use a heteroduplex oligonucleotide for improved potency, efficacy and longer retention times.

• Masaki Ohyagi
• Tetsuya Nagata
• Takanori Yokota

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Prestigious cancer research institute has retracted 7 studies amid controversy over errors

Seven studies from researchers at the prestigious Dana-Farber Cancer Institute have been retracted over the last two months after a scientist blogger alleged that images used in them had been manipulated or duplicated.

The retractions are the latest development in a monthslong controversy around research at the Boston-based institute, which is a teaching affiliate of Harvard Medical School. 

The issue came to light after Sholto David, a microbiologist and volunteer science sleuth based in Wales, published a scathing post on his blog in January, alleging errors and manipulations of images across dozens of papers produced primarily by Dana-Farber researchers . The institute acknowledged errors and subsequently announced that it had requested six studies to be retracted and asked for corrections in 31 more papers. Dana-Farber also said, however, that a review process for errors had been underway before David’s post. 

Now, at least one more study has been retracted than Dana-Farber initially indicated, and David said he has discovered an additional 30 studies from authors affiliated with the institute that he believes contain errors or image manipulations and therefore deserve scrutiny.

The episode has imperiled the reputation of a major cancer research institute and raised questions about one high-profile researcher there, Kenneth Anderson, who is a senior author on six of the seven retracted studies. 

Anderson is a professor of medicine at Harvard Medical School and the director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber. He did not respond to multiple emails or voicemails requesting comment. 

The retractions and new allegations add to a larger, ongoing debate in science about how to protect scientific integrity and reduce the incentives that could lead to misconduct or unintentional mistakes in research. 

The Dana-Farber Cancer Institute has moved relatively swiftly to seek retractions and corrections. 

“Dana-Farber is deeply committed to a culture of accountability and integrity, and as an academic research and clinical care organization we also prioritize transparency,” Dr. Barrett Rollins, the institute’s integrity research officer, said in a statement. “However, we are bound by federal regulations that apply to all academic medical centers funded by the National Institutes of Health among other federal agencies. Therefore, we cannot share details of internal review processes and will not comment on personnel issues.”

The retracted studies were originally published in two journals: One in the Journal of Immunology and six in Cancer Research. Six of the seven focused on multiple myeloma, a form of cancer that develops in plasma cells. Retraction notices indicate that Anderson agreed to the retractions of the papers he authored.

Elisabeth Bik, a microbiologist and longtime image sleuth, reviewed several of the papers’ retraction statements and scientific images for NBC News and said the errors were serious. 

“The ones I’m looking at all have duplicated elements in the photos, where the photo itself has been manipulated,” she said, adding that these elements were “signs of misconduct.” 

Dr.  John Chute, who directs the division of hematology and cellular therapy at Cedars-Sinai Medical Center and has contributed to studies about multiple myeloma, said the papers were produced by pioneers in the field, including Anderson. 

“These are people I admire and respect,” he said. “Those were all high-impact papers, meaning they’re highly read and highly cited. By definition, they have had a broad impact on the field.” 

Chute said he did not know the authors personally but had followed their work for a long time.

“Those investigators are some of the leading people in the field of myeloma research and they have paved the way in terms of understanding our biology of the disease,” he said. “The papers they publish lead to all kinds of additional work in that direction. People follow those leads and industry pays attention to that stuff and drug development follows.”

The retractions offer additional evidence for what some science sleuths have been saying for years: The more you look for errors or image manipulation, the more you might find, even at the top levels of science. 

Scientific images in papers are typically used to present evidence of an experiment’s results. Commonly, they show cells or mice; other types of images show key findings like western blots — a laboratory method that identifies proteins — or bands of separated DNA molecules in gels. 

Science sleuths sometimes examine these images for irregular patterns that could indicate errors, duplications or manipulations. Some artificial intelligence companies are training computers to spot these kinds of problems, as well. 

Duplicated images could be a sign of sloppy lab work or data practices. Manipulated images — in which a researcher has modified an image heavily with photo editing tools — could indicate that images have been exaggerated, enhanced or altered in an unethical way that could change how other scientists interpret a study’s findings or scientific meaning. 

Top scientists at big research institutions often run sprawling laboratories with lots of junior scientists. Critics of science research and publishing systems allege that a lack of opportunities for young scientists, limited oversight and pressure to publish splashy papers that can advance careers could incentivize misconduct. 

These critics, along with many science sleuths, allege that errors or sloppiness are too common , that research organizations and authors often ignore concerns when they’re identified, and that the path from complaint to correction is sluggish. 

“When you look at the amount of retractions and poor peer review in research today, the question is, what has happened to the quality standards we used to think existed in research?” said Nick Steneck, an emeritus professor at the University of Michigan and an expert on science integrity.

David told NBC News that he had shared some, but not all, of his concerns about additional image issues with Dana-Farber. He added that he had not identified any problems in four of the seven studies that have been retracted. 

“It’s good they’ve picked up stuff that wasn’t in the list,” he said. 

NBC News requested an updated tally of retractions and corrections, but Ellen Berlin, a spokeswoman for Dana-Farber, declined to provide a new list. She said that the numbers could shift and that the institute did not have control over the form, format or timing of corrections. 

“Any tally we give you today might be different tomorrow and will likely be different a week from now or a month from now,” Berlin said. “The point of sharing numbers with the public weeks ago was to make clear to the public that Dana-Farber had taken swift and decisive action with regard to the articles for which a Dana-Farber faculty member was primary author.” 

She added that Dana-Farber was encouraging journals to correct the scientific record as promptly as possible. 

Bik said it was unusual to see a highly regarded U.S. institution have multiple papers retracted. 

“I don’t think I’ve seen many of those,” she said. “In this case, there was a lot of public attention to it and it seems like they’re responding very quickly. It’s unusual, but how it should be.”

Evan Bush is a science reporter for NBC News. He can be reached at [email protected].

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Yale Research Team Awarded $4 Million Grant to Evaluate New Immunizations for Infant RSV

A multidisciplinary team of Yale scientists has received a $4 million federal grant to study the effectiveness of a new vaccine and monoclonal antibody shot designed to prevent respiratory syncytial virus (RSV) in infants.

The five-year grant from the National Institutes of Health will allow the researchers to investigate the interventions’:

• overall effectiveness
• durability in providing immunity
• effectiveness against different virus lineages
• effectiveness across age groups

Globally, RSV is second only to malaria as the leading cause of infant death. It is estimated that over 100,000 children under 5 die from RSV annually, half of them infants less than 6 months of age. In the United States, RSV is associated with 1.5 million annual medical encounters in children less than 5 years old and is the leading cause of hospitalization among infants under 1 year. It is the most common form of bronchitis and pneumonia among infants.

After years of trials and study, the U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention approved the use of two new tools to help protect infants from RSV in 2023. Nirsevimab , a long-acting monoclonal antibody, is the first drug of its kind to be used as part of a routine immunization program for infants. Abrysvo is the first vaccine to be specifically labeled for use in pregnant women to protect their infants from RSV disease

“The … introduction of new immunoprophylactic agents offers unique opportunities to confront the challenge of RSV in infants,” the researchers said in their project summary. “As is the case with any new vaccine, it will be important to conduct studies during the early phases of implementing these new immunization strategies to answer many unanswered questions surrounding their risks and benefits in real-world settings.”

Data collected in the study will inform health officials and policymakers on the optimal use of the new RSV preventative strategies and will help build public confidence in the immunization program, the researchers said.

The research team includes specialists in a variety of disciplines — vaccinology, clinical epidemiology, pediatric infectious diseases, viral genomics, bioinformatics, and translational immunology. A distinct feature of the project is that it will utilize a “vaccinomics” framework to study interactions between the virus, the vaccines, and the mother/child immune system. The researchers believe this approach will generate novel mechanistic data that will advance our understanding of the various factors that may contribute to diminished or maladaptive vaccine responses.

Carlos R. Oliveira, MD, PhD , an attending physician and specialist in pediatric infectious diseases at Yale New Haven’s Children Hospital, is principal investigator. Oliveira is an assistant professor of pediatrics (infectious diseases and global health), of biostatistics (health informatics), and of biomedical informatics & data science at both Yale School of Medicine (YSM) and the Yale School of Public Health (YSPH).

YSPH co-investigators on the project are Professor of Epidemiology of Microbial Diseases Linda Niccolai, PhD , Associate Professor of Epidemiology of Microbial Diseases Nathan Grubaugh, PhD, and Associate Professor of Epidemiology of Microbial Diseases Daniel Weinberger, PhD . Eugene Shapiro, MD , professor of pediatrics, of epidemiology, and of investigative medicine at both YSM and YSPH, is also a co-investigator along with Paul Aronson, MD , associate professor of pediatrics (emergency medicine), and Carrie Lucas, PhD , associate professor of immunobiology, both of YSM.

With the NIH funding, the research team plans to conduct a large-scale case-controlled study using data collected from an estimated 3,750 children one year of age or younger who receive care for acute respiratory illness at inpatient and outpatient clinical sites of the Yale New Haven Health System, the largest and most comprehensive health care system in Connecticut.

Data will be collected from multiple sources including health records, interviews, immunization registries, and population surveys. Investigators will also conduct genetic characterization of all RSV viruses identified in the study, monitor the genetic diversity of the virus over time, and quantify the relative effectiveness of the immunizations against various viral lineages.

• Vaccination

Featured in this article

• Carlos R Oliveira, MD, PhD Assistant Professor of Pediatrics (Infectious Diseases & Global Health), of Biostatistics (Health Informatics), and of Biomedical Informatics and Data Science; Director, Pediatric AIDS, and Congenital Infectious Diseases; Co-Lead of Yale Network of Vaccine Initiatives, Yale Institute for Global Health
• Linda Niccolai, PhD Associate Dean for Academic Affairs and Professor of Epidemiology (Microbial Diseases); Affiliated Faculty, Yale Institute for Global Health; Director, HPV Working Group at Yale; Director, CT Emerging Infections Program at Yale, Epidemiology of Microbial Diseases
• Nathan Grubaugh, PhD Associate Professor of Epidemiology (Microbial Diseases); Affiliated Faculty, Yale Institute for Global Health
• Eugene Shapiro, MD Professor of Pediatrics (General Pediatrics) and of Epidemiology (Microbial Diseases); Vice Chair for Research, Department of Pediatrics, Pediatrics; Deputy Director, Investigative Medicine PhD Program, Investigative Medicine Program; Co-Director of Education, Yale Center for Clinical Investigation, YCCI Senior Leadership; Affiliated Faculty, Yale Institute for Global Health
• Paul Aronson, MD, MHS Associate Professor of Pediatrics (Emergency Medicine); Deputy Director, Pediatric Residency Program; Director, Pediatric Emergency Medicine Elective, Pediatrics
• Carrie L Lucas, PhD Associate Professor of Immunobiology

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Paying Off People’s Medical Debt Has Little Impact on Their Lives, Study Finds

A nonprofit group called R.I.P. Medical Debt has relieved Americans of $11 billion in hospital bills. But that did not improve their mental health or their credit scores, a study found.

By Sarah Kliff

Over the past decade, R.I.P. Medical Debt has grown from a tiny nonprofit group that received less than $3,000 in donations to a multimillion-dollar force in health care philanthropy.

It has done so with a unique and simple strategy to tackling the enormous amounts that Americans owe hospitals: buying up old bills that would otherwise be sold to collection agencies and wiping out the debt.

Since 2014, R.I.P. Medical Debt estimates that it has eliminated more than $11 billion of debt with the help of major donations from philanthropists and even city governments. In January, New York City’s mayor, Eric Adams, announced plans to give the organization $18 million.

But a study published by a group of economists on Monday calls into question the premise of the high-profile charity. After following 213,000 people who were in debt and randomly selecting some to work with the nonprofit group, the researchers found that debt relief did not improve the mental health or the credit scores of debtors, on average. And those whose bills had been paid were just as likely to forgo medical care as those whose bills were left unpaid.

“We were disappointed,” said Ray Kluender, an assistant professor at Harvard Business School and a co-author of the study. “We don’t want to sugarcoat it.”

Allison Sesso, R.I.P. Medical Debt’s executive director, said the study was at odds with what the group had regularly heard from those it had helped. “We’re hearing back from people who are thrilled,” she said.

In a survey the group conducted last year, 60 percent of people with medical bills said the debt had negatively affected their mental health, and 42 percent said they had delayed medical care.

Studies had shown significant mental health and financial improvements for other types of debt relief, such as paying off student loans or mortgages . But those debts have more urgency: Homeowners who do not pay their mortgages could quickly lose their homes, whereas a hospital bill can languish for years with little consequence.

Major credit reporting agencies removed debts smaller than $500 from credit reports last year, further lessening the impact of outstanding debt. And the federal government is pursuing rules that would remove medical bills entirely from credit reports.

The study, published as a National Bureau of Economic Research working paper, is one of the first to look at the impact of medical debt relief on individuals. “It’s a big policy area right now, so its important to show rigorously what the results are,” said Amy Finkelstein, a health economist at the Massachusetts Institute of Technology whose research has shown significant positive effects of gaining health insurance.

Ms. Finkelstein is also a co-director of J-PAL North America, a nonprofit group that runs randomized experiments on social programs and provided some funding for this project.

“The idea that maybe we could get rid of medical debt, and it wouldn’t cost that much money but it would make a big difference, was appealing,” Ms. Finkelstein said. “What we learned, unfortunately, is that it doesn’t look like it has much of an impact.”

Mr. Kluender and one of his co-authors came up with the idea for the study in 2016 when they saw R.I.P. Medical Debt featured in a popular segment from John Oliver ’s television show. They and two other economists teamed up with the nonprofit group to run the experiment, which wiped out $169 million in debt from 83,000 debtors between 2018 and 2020.

Those patients, like others R.I.P. Medical Debt typically helps, were not making payments on those bills, which were at least a year old. The economists monitored the patients’ credit scores and sent them surveys asking questions about their mental health and the barriers they had faced in getting medical care.

They compared those results to a control group of 130,000 people who had not had their debts relieved, and they found few differences. The two groups reported similar financial barriers to seeking medical care and similar access to credit. The patients whose medical debts had been paid off were just as likely to have trouble paying other bills a year later.

“Many of these people have lots of other financial issues,” said Neale Mahoney, an economist at Stanford and a co-author of the study. “Removing one red flag just doesn’t make them suddenly turn into a good risk, from a lending perspective.”

For some in the study with no other debt in collections, the erased medical bills did lead to a 3.6-point bump in their credit score, on average.

The researchers were startled to find that for some people, particularly those who already had high levels of financial stress, debt relief worsened their depression. It’s possible, the researchers speculated, that being told about the sudden payoff had inadvertently reminded debtors of their other unpaid bills.

R.I.P. Medical Debt has “evolved” since 2020, when the experiment concluded, Ms. Sesso said. Major donations now allow the group to buy up billions in debt in a single city, which she said could have a larger impact on beneficiaries’ finances.

An earlier version of this article misstated the details of recent changes to credit reports. Credit agencies have voluntarily removed debts smaller than $500; they were not forced to by new federal rules.

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Sarah Kliff is an investigative health care reporter for The Times. More about Sarah Kliff