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Deep learning models that infer clinically relevant biomarker status from tissue images are being explored as rapid and low-cost alternatives to molecular testing. Here we show, through statistical analysis across multiple cancer types, datasets and modelling approaches, that the datasets used to train these models contain strong dependencies between biomarkers and clinicopathological features, which prevent models from isolating the effect of a single biomarker and lead them to learn confounded signals. Consequently, their prediction accuracy varies substantially with the status of codependent biomarkers and clinicopathological variables, and for several biomarkers, the gain over what a pathologist can already infer from routine histopathological features, such as grade, remains modest. These findings indicate that current approaches are not yet suitable as substitutes for molecular testing but can support triage or complementary decision-making with caution. Unconfounded biomarker prediction will require models that learn causal rather than correlational relationships between biomarkers and tissue morphology.
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This Medical News article discusses new state laws designed to relieve medical workforce shortages by waiving the requirement that internationally trained physicians receive residency training in the US before they can become licensed.
Insights from the Pulmonary Hypertension Global Patient Survey https://bit.ly/4m5MOaS.
With experimental burials, scientists are looking for chemical signposts that could help real-world investigations.
Metagenomic data provide evidence that bacteriophage (phage) abound in the enteric microbiomes of humans. However, the contribution of these viruses in shaping the bacterial composition of the gut microbiome and how these phages are maintained remain unclear. We performed experiments with 756 combinations of 54 Escherichia coli and nine phage isolates from four fecal microbiota transplantation (FMT) doses and five laboratory phages as samples of non-dysbiotic human enteric microbiota. We also developed a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our experiments predict that as a consequence of the production of the O antigen, most of the E. coli in the human enteric microbiome will be resistant to infections with the array of co-occurring phages. Our modeling suggests that phages are maintained in these enteric communities due to the high rates of transition between the O antigen-resistant and -sensitive states. Based on our observations and predictions from this theory, we postulate that the phage found in the human gut are likely to play a little role in shaping the strain composition of E. coli of healthy individuals. Although we only investigated E. coli, the mechanism of resistance described here is shared among most of the gram-negative bacteria. Evidence is provided that, as a consequence of O antigen-mediated resistance, the genetically diverse array of bacteriophage in the gut microbiome of humans plays little or no role in determining the densities and distribution of the genetically diverse strain E. coli in this habitat. Our mathematical model predicts and our experiments support the hypothesis that the phage present in the gut microbiome are maintained by replication on the minority of sensitive bacteria generated by the leakiness of O antigen-mediated resistance.IMPORTANCEBacteriophages (phages) are abundant in the human gut, yet whether these viruses shape the bacterial communities living there remains unresolved. Using Escherichia coli and phages isolated from the stool of healthy fecal microbiota transplantation (FMT) donors, together with a mathematical model, we show that the vast majority of gut E. coli are resistant to co-occurring phages because they express the O antigen, a surface structure that masks the receptors phages use to attach. Despite this widespread resistance, phages persist by replicating on a small, continually regenerated subpopulation of sensitive cells, a phenomenon we term leaky resistance. These findings suggest that phages play a little role in determining which E. coli strains dominate the healthy human gut. Because the O antigen is broadly expressed across gram-negative bacteria, this mechanism likely extends well beyond E. coli and helps explain why isolating therapeutic phages against many pathogens is difficult.
Polygenic indices (PGIs) of various traits abound, but knowledge remains limited on how they predict wide-ranging health indicators, including the risk of death. We investigated the associations between mortality and 35 different PGIs related to social, psychological, and behavioural traits, and typically non-fatal health conditions. Data consist of Finnish adults from population-representative genetically informed epidemiological surveys (FINRISK 1992-2012, Health 2000/2011, FinHealth 2017), linked to administrative registers (N: 40,097 individuals, 5948 deaths). Within-sibship analysis was complemented with dizygotic twins from Finnish twin study cohorts (N: 10,174 individuals, 2116 deaths). We estimated Cox proportional hazards models with mortality follow-up 1995-2019. PGIs most strongly predictive of all-cause mortality were ever smoking (hazard ratio [HR]=1.12, 95% confidence interval [95% CI] 1.09; 1.14 per one standard deviation larger PGI), self-rated health (HR = 0.90, 95% CI 0.88; 0.93), body mass index (HR = 1.10, 95% CI 1.07; 1.12), educational attainment (HR = 0.91, 95% CI 0.89; 0.94), depressive symptoms (HR = 1.07, 95% CI 1.04; 1.10), and alcohol drinks per week (HR = 1.06, 95% CI 1.04; 1.09). Within-sibship estimates were approximately consistent with the population analysis. The investigated PGIs were typically more predictive for external than for natural causes of death. PGIs were more strongly associated with death occurring at younger ages, while among those who survived to age 80, the PGI-mortality associations were negligible. PGIs related to the best-established mortality risk phenotypes had the strongest associations with mortality. They offer moderate additional prediction even when mutually adjusting with their phenotype. HL was supported by the European Research Council [grant #101019329] as well as the Max Planck - University of Helsinki Center for Social Inequalities in Population Health. SL gratefully acknowledges funding from the Research Council of Finland (# 350399). PM was supported by the European Research Council under the European Union's Horizon 2020 research and innovation programme (#101019329), the Strategic Research Council (SRC) within the Research Council of Finland grants for ACElife (#352543-352572) and LIFECON (#345219), the Research Council of Finland profiling grant for SWAN (#136528219) and FooDrug (# 136528212), and grants to the Max Planck - University of Helsinki Centre for Social Inequalities in Population Health from the Jane and Aatos Erkko Foundation (#210046), the Max Planck Society (# 5714240218), University of Helsinki (#77204227), and Cities of Helsinki, Vantaa and Espoo (#4706914). The study does not necessarily reflect the Commission's views and in no way anticipates the Commission's future policy in this area. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Canine parvovirus (CPV) enteritis is a widespread infectious disease affecting dogs globally. While vaccination is an acceptable preventive measure, repeated cases of vaccination and immunization failures abound globally, posing a significant challenge to veterinary practice. Therefore, a clinic-based cross-sectional study of dogs presenting with acute gastroenteritis, aimed at identifying factors associated with CPV breakthrough infection in Nigeria was conducted. This study involved demographic with retrospective data of historical vaccination of gastroenteritis-presenting dogs from selected veterinary clinics. The dogs were sampled from 10 veterinary clinics from multiple locations in Nigeria, including Abeokuta, Abuja, Ibadan, Jos, Makurdi, Onitsha, and Warri. The cases were initially screened using an immunochromatographic assay and validated with polymerase chain reaction (PCR) assay. Data on signalment, vaccination history, and protocol compliance were collected from 158 cases between June 2016 and March 2018. Statistical associations were analyzed using Chi-square test and binary logistic regression to identify predictors of CPV-2 breakthrough infection. Result showed that among the gastroenteritis dogs, 93.7% (146/158) tested positive for CPV-2, with cases mostly affecting puppies aged 0-6 months (69.6%). Significant univariate predictors of infection included clinic location (p = .017) and vaccination status (p = .02). In vaccinated dogs, critical factors for breakthrough infection were the number of vaccine doses (p = .036), vaccination finish time (p = .002), and overall protocol compliance (p < .001). Logistic regression score test further identified breed (particularly Rottweilers, p < .001), age (p = .019), vaccine brand mixing within puppy primary series (p = .026), and the presence of concurrent infections (p = .026) as significant factors. However, due to quasi-complete separation and small effective sample size (n = 17), multivariable logistic regression results were unstable and are presented here for exploratory purposes only. Furthermore, clinical cases with single-, double-, triple-, and quadruple-dose protocol showed breakthrough infection rates in the following decreasing order, 31.0%, 17.1%, 12.0%, and 0.6%, respectively. This high rate of CPV-2 breakthrough infection suggests that vaccination protocols used in high-challenge environments may require review. Therefore, these findings show that completing the puppy primary vaccination series at or after 16 weeks of age was significantly associated with a lower rate of breakthrough infection compared to finishing earlier. Adherence to strict dosing intervals and consideration of breed-specific risks may be essential to reduce breakthrough infection rate in Nigeria. These results suggest potential gaps in vaccination timing and compliance and this may contribute to increased risk of CPV infection in Nigeria.
From aggressive billing practices to neglectful or discriminatory care, news stories about the misconduct of healthcare organizations abound. Yet there has been limited ethical scrutiny of hospitals and other healthcare organizations in the bioethics literature. In this paper, we explore what philosophy and organizational theory can offer in terms of concepts for articulating the obligations of healthcare organizations, specifically hospitals. We highlight how the concepts of institutional agency and responsibility, administrative harms and burdens, and communicative blame provide theoretical resources that can help bioethics get closer to a more robust organizational ethics. We advance two claims: first, these concepts help us make sense of how hospitals or healthcare organizations-not just individuals and the broader systems they operate within-can be morally responsible or blameworthy. Second, critical reflection on these concepts as they apply to several historical examples suggest some prima facie obligations of organizations that provide patient care.
Negative misconceptions about the inevitability of declining physical health and cognitive functioning in old age abound in society and in literature on autistic ageing. But there is a paradox of ageing: most older adults in the general population experience increases in life satisfaction and emotional wellbeing in later life that are associated with quality of life and indicative of successful ageing. Parallel patterns of later-life improvement in psychosocial functioning and emotional wellbeing have been found in attention deficit hyperactivity disorder and schizophrenia, which raises the tantalising question: could the paradox of ageing be true for older autistic adults too? Contemporary gerontological research that reconciles the contradictions inherent in this paradox from a lifespan developmental psychology perspective also informs global public health initiatives. These promote healthy successful ageing as a process of recovery, adaptation and growth in later life for people of all abilities. By contrast, there has been relatively little examination of autistic ageing from this perspective. Drawing on analyses of both gerontological and autism literature, this gap is addressed. Lifespan psychology's potential relevance to the developmental trajectory of autism is explored, and an evidence-based theoretical framework to guide future autism research and clinical practice aimed at promoting successful autistic ageing is proposed.Lay AbstractWhat is already known about this topic?Despite experiencing physical and mental losses as they age, most older people are satisfied with life. They have more positive than negative emotions, and this is related to wellbeing and improved quality of life. According to lifespan psychology, this unexpected pattern is evidence of successful ageing. By contrast, the potential for successful ageing in autism is not well understood. Even though it informs the World Health Organization's guidelines on healthy ageing, there has been relatively little consideration of lifespan psychology in relation to autistic ageing. The researchers' aim was to address this gap.What does this article add?This article provides a novel approach to understanding and promoting successful autistic ageing. It describes lifespan psychology and associated models and theories and how they relate to autistic experience. It also explains how and why positive outcomes like quality of life and life satisfaction are realistic goals for older autistic adults.Implications for practice, research or policyLifespan psychology offers an evidence-based framework for guiding future research, policy and clinical practice to help older autistic adults achieve positive life outcomes, productivity, personal growth and wellbeing. Future research should test whether autistic older adults experience the same improvements in social and emotional wellbeing in later life as other groups in the population. This will help to make sure that health policy and clinical support are not based on negative assumptions about autistic ageing that do not reflect real-life experiences. Most importantly, this article shows that by thinking about ageing differently, there are opportunities for all autistic adults to enjoy healthy successful ageing.
Objectives: Cardiometabolic risk factors are prevalent in the United States, and their association with cognitive outcomes is well-established. Opportunities to elucidate the unique and combined contributions of cardiometabolic burden to cognition are abound. Importantly, investigating the cognitive changes incurred as burden increases has scientific and clinical implications. Methods: Older adults (M = 69.3, SD = 8.35) from the National Neuropsychology Network (N = 4222) were included. Cardiometabolic burden, defined via ICD-10 diagnostic codes, and performance on cognitive measures were the primary variables. Domain-level cognitive differences were calculated using a multigroup confirmatory factor analysis. Structural equation modeling evaluated associations between cardiometabolic burden and cognition, adjusting for demographic characteristics. Results: Relative to those without cardiometabolic burden, persons with one condition performed worse on measures of attention and working memory (p < .001, d = 0.24) and visuoconstructional and visuoperceptual abilities (p < .01, d = 0.19), persons with two conditions performed worse on measures of language (p < .01, d = 0.24), attention and working memory (p < .01, d = 0.23), executive function (p < .001, d = 0.22), and visuoconstructional and visuoperceptual abilities (p < .01, d = 0.23), and persons with three or more conditions performed worse across all domains except language and immediate memory (drange = 0.27-0.48). The impact of demographic characteristics on cognition differed by domain, but higher education was consistently associated with higher cognitive scores. Conclusions: Cognitive performance declined with increasing cardiometabolic burden. More education was associated with higher cognitive scores. Our findings contribute to the literature linking cardiometabolic risk management and cognitive health. Future studies should investigate whether targeting specific cardiometabolic risk factors would effectively improve cognitive function longitudinally.
Economic inequality is a critical issue in elections and legislating, so having an informed electorate is vital to sensible policymaking. Unfortunately, misperceptions about the true extent of inequality abound. Here, we demonstrate that the most prevalent formats for representing economic distributions tend to dampen viewer impressions of inequality. We begin by showing that the most popular newspaper portrayals of inequality contain potentially biasing features. Next, in nine experiments (N = 3599 U.S. adults), we explore how these common representations of inequality evoke biased impressions and we test methods to mitigate these biases. Specifically, we document two biases in how people evaluate economic distributions. First, people are under-sensitive to differences in the size of identified population groups (e.g., top 1% vs. top 10%) such that their judgments become distorted by arbitrary ways in which a population is divided (partition dependence). Second, people's judgments under-weight information about intermediate groups relative to the most- and least-wealthy groups (middle neglect). We test ways to mitigate these biases and conclude by proposing presentation guidelines that promote more accurate impressions.
Opportunities abound in microfluidic technologies to impact how we understand extremely complex systems with many constituents which change with time and space. In these technologies, separation science plays a central role towards understanding everything from biology and healthcare to environmental monitoring to the search for life in the Solar system. Separations can amplify the capabilities of detection modalities by isolating targets and/or increasing their concentration while removing background constituents which can interfere with their sensing. In essence, separations increase the amount of information that can be gathered from a sample. The ideal features of next-generation separations capability are present in gradient insulator-based dielectrophoresis (g-iDEP), enabled by the length scale and precision of microfluidics. It acts through electric field interactions with particles, which enables unbiased (label-free) separations since all relevant particles, from atoms to cells, have an accessible response to electricity-either through linear (electrophoresis) or higher-order gradient (dielectrophoresis and related) effects. The technique isolates and concentrates, enabling improved detection function and multidimensional separations. Its foundational theoretical capabilities give it separations power on the order of 1:108, beyond the resolving power of the best mass spectrometers and ultra-high resolution spectroscopies. Experimental evidence is amassing that shows it to be a powerful tool that can resolve tiny differences in cells (antibiotic resistance versus susceptible in unlabeled paired isolates across many species) and differentiate single-point mutations in proteins. Its capabilities are still emerging, and this work aims to quantify the current practice and connect those approaches to the ultimate capabilities of the technique towards quantifying the dynamic range and resolving power of the strategy as a whole. The technique uses two methods of quantifying the electrophysical properties of the target, voltage sweep and spatial methods. The voltage sweep method is lower-resolution and serves as a search mode, while the spatial method is higher-resolution and quantifies the properties over a smaller defined range determined via the sweep method. These quantification methods are examined by collating existing experimental data, performing relevant Monte Carlo simulations, and finite element model calculations. These are summarized to understand the mechanisms currently limiting the technique, facilitate quantitative comparisons with traditional separation science capabilities in terms of resolution and dynamic range, and compare them to the theoretical limits of the strategy.
Pharmacists, while central to medication safety, face underestimated risks due to their daily exposure to toxic and explosive substances. In compounding pharmacies, handling carcinogenic, mutagenic, and reprotoxic (CMR) substances such as chemotherapy drugs, anesthetic gases, antibiotics, and hormones poses significant health hazards. These substances can cause environmental and secondary contamination through fine powder dispersion or volatile vapors, leading to indirect exposure even with standard protective gear. Explosive and fire risks also abound, especially with volatile solvents like ethanol, acetone, and ethyl ether. These substances are flammable and require careful storage and handling. Accidental chemical reactions, such as the mixing of acids and bases or contact between unstable compounds like picric acid and friction, can result in toxic gas release or explosions. To mitigate these dangers, pharmacies must implement strict preventive measures. This includes the use of fume hoods, appropriate personal protective equipment (PPE), and standardized protocols for hazardous drug preparation. Flammable substances must be stored in ventilated, ATEX-compliant cabinets, and chemicals clearly labeled with updated safety data sheets (SDS). Safe waste management and continuous staff training are also essential. Current challenges, such as drug shortages, force pharmacies to work with unfamiliar raw materials, increasing the risk of accidents. A notable example is potassium clavulanate, a fine powder prone to dust explosions if not carefully managed. Ultimately, ensuring pharmacist safety requires a culture of vigilance, continuous education, and adherence to safety protocols to manage both toxicological and explosive risks effectively.
When environments change and phenotypes become suboptimal, organisms often mitigate the costs of maladaptation with behavioural adjustments. Although this "buffering" of natural selection is widespread, its evolutionary consequences are poorly understood. Here, I use evolutionary simulations to explore how behavioural plasticity shapes the tempo and mode of adaptive evolution. My results indicate that this fast-acting form of plasticity enhances persistence under suboptimal conditions and facilitates the accumulation of genetic variation within populations. Over short timescales, or when opportunities for niche expansion are limited, the combined action of these effects leads to slower evolution of morphology and physiology. Over longer timescales, or when ecological opportunities abound, it can instead lead to a "Goldilocks" pattern, where evolution is fastest in moderately plastic lineages, whose medium buffering capacity enables persistence in suboptimal conditions without severely constraining subsequent optimizing selection. These findings expose key differences in scope and mechanism relative to other forms of phenotypic plasticity and suggest that behavioural plasticity may more broadly influence the evolutionary trajectories of individual lineages. More generally, they help clarify our understanding of how short-term flexibility shapes long-term adaptation and underscore the need to reassess current risk-assessment frameworks that equate slower evolutionary rates with greater vulnerability to environmental change.
As humans, we store and share information. This allows us to distribute knowledge necessary for survival and to coordinate large groups. Our hominin ancestors harnessed the surfaces of mobile artifacts and cave walls as information carriers since the Paleolithic time period. Theories abound as to the meaning and function of these Paleolithic signs. However, very little is known about their basic, measurable properties. We here analyze a corpus of more than 200 mobile objects of a 43,000 to 34,000 y old Aurignacian culture-associated with the first modern humans to settle in Central Europe. These objects are adorned with several thousand geometric signs. We apply classification algorithms and statistical models to capture their quantitative properties. First, our analyses illustrate that these sign sequences are clearly distinguishable from modern day writing. Second, however, their statistical properties are comparable to sign sequences on the earliest protocuneiform tablets. Third, Paleolithic signs were systematically applied to yield higher information density on certain types of objects, e.g. ivory figurines compared to tools. These results cannot be taken to strictly prove that Aurignacian sign sequences encoded numero-ideographic information as in the case of protocuneiform. However, they prove that the first hunter-gatherers arriving in Europe already applied sign sequences of comparable complexity in a deliberate, systematic, and conventional manner-several ten thousand years before the advent of genuine writing.
Rabies is an acute, progressive, viral encephalitis. Warm-blooded vertebrates are susceptible. Major reservoirs reside in the Chiroptera and Carnivora. Among the latter, representatives include dogs, ferret badgers, foxes, jackals, mongooses, raccoons, and skunks. Within the Carnivora, pinnipeds represent a diverse group of >30 extant species. These marine mammals range from the Arctic to Antarctica, but there is no review about rabies in this group. Apparently, only a single 1980 case of rabies occurred from Svalbard in a ringed seal (Phoca hispida). However, in 2024, incidental cases appeared within South African Cape fur seals (Arctocephalus pusillus). Retrospective testing of archival material identified suspect cases dating back to 2022. Currently, more than 80 cases have been documented in seals. Moreover, a new 2025 focus appeared in Namibia and cases in Angola are predictable. Viral characterization supports spillover infection via rabid black-backed jackals (Lupulella mesomelas). A host shift appears likely, with ongoing seal intraspecific transmission. Given the unique nature of this epizootic, implications for the southern hemisphere abound. Unfortunately, comprehensive data are lacking on pinniped specimens examined outside of southern Africa. For example, although Antarctica is considered 'rabies-free', minimal international standards for support are unmet. No routine laboratory-based surveillance occurs. This enzootic rabies focus among seals in southern Africa presents unique challenges for the region and a rare opportunity for considering broader surveillance. Besides targeted parenteral vaccination of fur seals, local engagement involves vagrant species, including elephant (Mirounga leonina) and leopard seals (Hydrurga leptonyx). The void of regional pinniped surveillance, especially encompassing the Southern Ocean would require considerable proactive local resolution and much wider collaboration regarding future concerns to both public health and conservation biology.
Human genetics has proven remarkably productive in linking genetic variants to a wide variety of diseases. Discovery initiatives from medical and population genetics have been especially prolific in generating new leads that point to underlying mechanisms of immune-mediated inflammatory diseases. While synthesizing leads from genetics into a functional understanding of disease pathophysiology is gaining momentum, challenges and opportunities abound. Here, we review advancements from combined efforts in functional genomics and chemical biology to construct and dissect mechanisms of mucosal immunity based on the genetics of inflammatory bowel disease (IBD). Taken together, a framework is emerging for interpreting disease mechanisms and conceiving new therapeutic hypotheses.
Conversations abound about how artificial intelligence (AI) is changing the world. AI and its applications are advancing at a pace that outstrips regulatory and ethical frameworks. In the face of these challenges, higher education must develop students into fluent, intelligent, and ethical users of AI and work to ensure that the benefits of AI reach broadly across communities.