bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives on early health economic evaluations of RNA therapies targeted at lipoprotein(a)
Authors: Burvill Angela , Watts Gerald F. , Ademi Zanfina
Published: February 2025

Purpose of review

Early health economic evaluations of new medications are useful, as they consider the implications for health services.

We reviewed recent literature on expected clinical outcomes of lowering of elevated plasma lipoprotein(a) [Lp(a)] in secondary prevention, which is essential information on effectiveness for economic evaluations.

We reviewed a recent early economic evaluation of RNA therapies targeted at Lp(a).

Recent findings

RNA-based therapies, if approved, would likely be used initially in adults with established atherosclerotic cardiovascular disease (ASCVD) and very high Lp(a). Adults with ASCVD have high absolute risk of recurrent events and elevated Lp(a) serves as a risk-enhancing factor.

Potent lowering of Lp(a) in secondary prevention may be associated with significant relative risk reductions of coronary heart disease or ASCVD events; this needs confirmation in currently ongoing and future clinical trials.

One economic evaluation has estimated the value of olpasiran and pelacarsen, at various willingness-to-pay thresholds, compared with standard-of-care secondary prevention.

Early economic evaluations estimate longer-term clinical benefits and cost consequences associated with new medications.

Existing casual evidence of Lp(a) and cardiovascular disease can be used in early economic evaluations as best available evidence, while awaiting results from major cardiovascular outcomes trials.
Serum Exosomal miR-216a Contributes to Acute Pancreatitis-Associated Acute Lung Injury by Enhancing Endothelial cell Vascular Permeability via Downregulating LAMC1
Authors: Zhu Huiyun , Zhou Xianzhu , Sun Xingcheng , Fu Chunting , Li Ge , Dong Xiaoyang , Kong Xiangyu , Su Xiaoju , Du Yiqi
Published: February 2025

Background:

Acute pancreatitis (AP) is an internal medical emergency disease, with fatal complications including acute lung injury (ALI). Recent studies have highlighted the critical roles of exosomal microRNAs (miRNAs) in AP-ALI. In the present study, we aim to investigate the role of serum exosomal miR-216a in AP-ALI and its underlying mechanisms.

Methods:

The levels of miR-216a in patients and rat models with AP and AP-ALI were assessed via real-time quantitative PCR (qRT-PCR) analysis. Patient and rat blood exosomes were isolated and co-cultured with HUVECs. The permeability of HUVECs was evaluated via trans-endothelial electrical resistance (TEER) assay. Bioinformatics predicting and luciferase reporter assays were used to identified potential targets of miR-216a. In addition, miR-216a mimic and LAMC1 overexpressed plasmid were constructed to identify the effects of miR-216a/LAMC1 axis on endothelial cell permeability in vitro. Anti-miR-216a and exosomes were used to identify the critical role of exosomal miR-216a in AP-ALI in vivo.

Results:

The findings indicated that there was a significant upregulation of miR-216a in AP-ALI patients and rat models. The occurrence of ALI during AP progression promoted the expression of serum exosomal miR-216a. Exosomal could promote HUVECs permeability by releasing miR-216a. For target studies, miR-216a was found to bind to LAMC1 to regulate its transcription level. MiR-216a-mediated downregulation of LAMC1 lead to increased permeability of HUVECs. Exosome-derived miR-216a has also been proved to promote lung damage in AP-ALI rats.

Conclusions:

In summary, serum exosomal miR-216a can promote the onset and progression of AP-ALI by augmenting endothelial cell vascular permeability. This finding presents a theoretical basis for exploring new therapeutic approaches targeting AP-ALI.
Association Between Nurse Turnover and Nurses’ Perception of Patient Outcomes in Acute Care Hospitals in South Korea
Authors: Bae Sung-Heui
Published: February 2025

Background:

High turnover rates among nurses are a global concern. Previous studies show the negative impact on quality of care.

Purpose:

The purpose of this study was to examine the relationship between nurse turnover and nurse’s perceptions of patient outcomes.

Methods:

A cross-sectional study design was used. Nurses working in 35 general hospitals in South Korea were invited to participate in a survey assessing their perceptions of patient outcomes, including quality of care, patient safety, and adverse events. Nurse turnover was measured for the prior 6 months.

Results:

Data from 159 nurses were analyzed. There was a significant positive relationship between turnover rates and perceptions of poor quality of care, after controlling for demographic and work-related characteristics. Nurse turnover was not significantly associated with perceptions of patient safety or adverse events.

Conclusions:

The negative consequence of nurse turnover on patient outcomes is partially supported in this study.
Diagnostic Performance of Spurling’s Test for the Assessment Sub-acute and Chronic Cervical Radiculopathy: A Systematic Review and Meta-Analysis
Authors: Lin Long-Huei , Lin Ting-Yu , Chang Ke-Vin , Tzang Chih-Chen , Wu Wei-Ting , Özçakar Levent
Published: February 2025

Objective

Spurling’s test (ST) is commonly used to diagnose cervical radiculopathy (CR); however, its diagnostic accuracy varies across studies. This systematic review and meta-analysis aim to evaluate the diagnostic performance of ST for CR.

Design

A systematic search of PubMed, ClinicalTrials.gov, Cochrane Library, and Physiotherapy Database was conducted following PRISMA guidelines. Studies assessing ST against imaging or electrodiagnostic tests were included. A bivariate random-effects model calculated pooled sensitivity, specificity, likelihood ratios (LR), and log diagnostic odds ratios.

Results

Eight studies met the inclusion criteria. The pooled sensitivity of ST was 0.53 (95% confidence interval [CI]: 0.29–0.78), higher with imaging (0.67) than with electrodiagnostic testing (0.31). Combining neck rotation or extension increased sensitivity to 0.67, compared to 0.31 without. The pooled specificity was 0.92 (95% CI: 0.88–0.96), 0.93 with imaging and 0.91 with electrodiagnostic testing. The pooled positive LR was 3.28, negative LR was 0.28, and the log diagnostic odds ratio was 2.74.

Conclusions

ST is highly specific but has low sensitivity for CR diagnosis, making it better suited for confirmation than screening. Sensitivity may improve with added maneuvers and imaging as a reference.
Physical activity is associated with better cognitive measures of verbal fluency, immediate recall, delayed recall, and numeracy in older people with osteoarthritis and moderate-severe pain
Authors: Ogrezeanu Daniel C. , Núñez-Cortés Rodrigo , Andersen Lars Louis , López-Bueno Rubén , Suso-Martí Luis , Salazar-Méndez Joaquín , Cruz-Montecinos Carlos , Calatayud Joaquín
Published: February 2025

Objective

This cross-sectional study assesses the relationship between physical activity (PA) and crucial indicators of cognitive function in older adults with osteoarthritis and moderate-severe pain.

Design

Data were derived from the 9th wave of the Survey of Health, Ageing and Retirement in Europe (SHARE), conducted among older people in 27 European countries and Israel. Cognitive measures of verbal fluency, immediate recall, delayed recall, and numeracy were included, as well as self-reports of PA level. Multivariable linear regression analysis was applied to test associations, adjusted for various demographic and lifestyle factors.

Results

7,429 participants were included. A positive association was found between performing moderate PA more than once a week and better verbal fluency (β = 2.16; 95%CI: 1.75-2.58), immediate recall (β = 0.51; 95%CI: 0.41-0.60), delayed recall (β = 0.45; 95%CI: 0.34-0.57) and numeracy (β = 0.43; 95%CI: 0.34-0.52) compared to hardly ever or never performing PA. Additionally, a positive but weaker association was found between performing vigorous PA once a week and better verbal fluency (β = 1.52, 95%CI: 1.02-2.02), immediate recall (β = 0.29, 95%CI: 0.18-0.41), delayed recall (β = 0.41, 95%CI: 0.27-0.54) and numeracy (β = 0.33, 95%CI: 0.23-0.44).

Conclusions

Regular PA, particularly moderate intensity, is positively associated with better cognitive measures of verbal fluency, immediate recall, delayed recall, and numeracy, with the strongest benefits observed for verbal fluency.
Habitat fragmentation enhances microbial collective defence
Authors: Verdon Nia , Popescu Ofelia , Titmuss Simon , Allen Rosalind J.
Published: February 2025

Microbes often inhabit complex, spatially partitioned environments such as host tissue or soil, but the effects of habitat fragmentation on microbial ecology and infection dynamics are poorly understood. Here, we investigate how habitat fragmentation impacts a prevalent microbial collective defence mechanism: enzymatic degradation of an environmental toxin. Using a theoretical model, we predict that habitat fragmentation can strongly enhance the collective benefits of enzymatic toxin degradation. For the example of

β

-lactamase-producing bacteria that mount a collective defence by degrading a

β

-lactam antibiotic, we find that realistic levels of habitat fragmentation can allow a population to survive antibiotic doses that greatly exceed those required to kill a non-fragmented population. This ‘habitat-fragmentation rescue’ is a stochastic effect that originates from variation in bacterial density among different subpopulations and demographic noise. We also study the contrasting case of collective enzymatic foraging, where enzyme activity releases nutrients from the environment; here we find that increasing habitat fragmentation decreases the lag time for population growth but does not change the ecological outcome. Taken together, this work predicts that stochastic effects arising from habitat fragmentation can greatly enhance the effectiveness of microbial collective defence via enzymatic toxin degradation.
The fundamental role of mitochondria–endoplasmic reticulum contacts in ageing and declining healthspan
Authors: Monaghan Richard M.
Published: February 2025

This open question research article highlights mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), which have emerged as crucial cellular structures that challenge our traditional understanding of organelle function. This review highlights the critical importance of MAMs as a frontier in cell biology with far-reaching implications for health, disease and ageing. MAMs serve as dynamic communication hubs between the ER and mitochondria, orchestrating essential processes such as calcium signalling, lipid metabolism and cellular stress responses. Recent research has implicated MAM dysfunction in a wide array of conditions, including neurodegenerative diseases, metabolic disorders, cardiovascular diseases and cancer. The significant lack of biological knowledge behind MAM function emphasizes the need to study these enigmatic subcellular sites in greater detail. Key open questions include the mechanisms controlling MAM formation and disassembly, the full complement of MAM-associated proteins and how MAMs contribute to cellular decision-making and ageing processes. Advancing our understanding of MAMs through interdisciplinary approaches and cutting-edge technologies promises to reveal new insights into fundamental cellular signalling pathways and potentially lead to innovative therapeutic strategies for a range of diseases. As such, MAM research represents a critical open question in biology with the potential to transform our understanding of cellular life and human health.
Novel, nanomagnetic and recoverable copper(0)-catalyst in one-pot access to 1,4-disubstituted 1,2,3-triazoles and 5-substituted 1
H
-tetrazoles in water
Authors: Amiri Mohammad , Bagherzadeh Nastaran , Sardarian Ali Reza
Published: February 2025

A novel Fe
3
O
4
@SiO
2
-Pr-2-Py-Cu(0) complex was produced as a heterogeneous magnetic nanocatalyst and characterized by employing several spectroscopic methods such as XRD, FT-IR, BET, VSM, FE-SEM, ICP, TGA, EDX, mapping, and UV-Vis spectroscopy. The catalytic performance of this novel catalyst was examined for efficient access to diverse 1,4-disubstituted-1,2,3-triazoles via eco-friendly one-pot three-component reactions of sodium azide, various terminal alkynes, and benzyl, allyl, ester, or alkyl halide in aqueous media and mild conditions. In addition, catalyst activity to study the generality and scope of the reaction in the library preparation of 5-substituted 1
H
-tetrazoles with a variety of electron-withdrawing and electron-donating groups was used through a one-pot reaction of hydroxylamine hydrochloride, diverse aldehydes and sodium azide in water. Catalyst recyclability results showed that it could operate up to eight consecutive runs without a significant reduction in the reaction efficiency. This green strategy assigns substantial advantages such as efficient and environmentally benign procedures, chemical waste minimization, stability and cost-effectiveness, short reaction time, wide-ranging substrate, an excellent yield of desired products and recoverable and reusable nanomagnetic catalysts.
A continuum theory of twinning-transformation toughening
Authors: Ma Lifeng , Korsunsky Alexander M. , Hills David A.
Published: February 2025

In this article, the twinning-induced toughening problem is addressed in the framework of plane strain. The fundamental solution for a pointwise twinning eigenstrain located in an infinite plane is derived first. With this solution, problems of twinned inclusions are formulated using the Green’s function method, and the interaction problem is solved for a crack-tip with a twinning point source (strain nucleus). Based on this solution, a continuum formulation for twinning-induced toughening is also developed using the Green’s function method. Finally, some examples are presented to demonstrate the validity and relevance of the fundamental formulations proposed in the paper. In comparison with the conventional approaches, this continuum framework of twinning-induced toughening provides a well-rounded understanding of the toughening mechanisms in crystalline materials. It enables the prediction and optimization of the material behaviour under various loading conditions.
How will we prepare for an uncertain future? The value of open data and code for unborn generations facing climate change
Authors: Gomes Dylan G. E.
Published: February 2025

As the impacts of climate change continue to intensify, humans face new challenges to long-term survival. Humans will likely be battling these problems long after 2100, when many climate projections currently end. A more forward-thinking view on our science and its direction may help better prepare for the future of our species. Researchers may consider datasets the basic units of knowledge, whose preservation is arguably more important than the articles that are written about them. Storing data and code in long-term repositories offers insurance against our uncertain future. To ensure open data are useful, data must be FAIR (Findable, Accessible, Interoperable and Reusable) and be complete with all appropriate metadata. By embracing open science practices, contemporary scientists give the future of humanity the information to make better decisions, save time and other valuable resources, and increase global equity as access to information is made free. This, in turn, could enable and inspire a diversity of solutions, to the benefit of many. Imagine the collective science conducted, the models built, and the questions answered if all of the data researchers have collectively gathered were organized and immediately accessible and usable by everyone. Investing in open science today may ensure a brighter future for unborn generations.
Rapid evolution of prehistoric dogs from wolves by natural and sexual selection emerges from an agent-based model
Authors: Elzinga David C. , Kulwicki Ryan , Iselin Samuel , Spence Lee , Capaldi Alex
Published: February 2025

Wolves are among the earliest animals to be domesticated. However, the mechanism by which ancient wolves were domesticated into modern dogs is unknown. Most of the prevailing domestication hypotheses posit that humans selectively bred wolves that were more docile. However, a competing hypothesis states that wolves that were less hostile towards humans would essentially domesticate themselves by naturally selecting for tamer wolves since that would allow for easier access to food from human settlements. A major critique of the latter hypothesis is whether evolution by this natural selective pathway could have occurred in a sufficiently short time span. Simulating the process would help demonstrate if such an objection is sufficient to dismiss this hypothesis. Thus, we constructed an agent-based model of the evolution of a single trait, a measure of human tolerance, in canines to test the merit of the time constraint objection. We tested scenarios both with and without mate preference to provide a potential sexual selective force. We used fecundity and mortality rates from the literature for validation. Hartigan’s dip test of unimodality was used to measure if and when divergence of populations occurred. Our results indicate that the proto-domestication hypothesis cannot be rejected on the basis of time constraints.
Cytoplasmic incompatibility factor proteins from
Wolbachia
prophage are costly to sperm development in
Drosophila melanogaster
Authors: Kaur Rupinder , Bordenstein Seth R.
Published: February 2025

The symbiosis between arthropods and
Wolbachia
bacteria is globally widespread, largely due to selfish-drive systems that favour the fitness of symbiont-transmitting females. The most common drive, cytoplasmic incompatibility (CI), is central to arboviral control efforts. In
Drosophila melanogaster
carrying
w
Mel
Wolbachia
deployed in mosquito control, two prophage genes in
Wolbachia, cifA
and
cifB
, cause CI that results in a paternal-effect lethality of embryos in crosses between
Wolbachia
-bearing males and aposymbiotic females. While the CI mechanism by which Cif proteins alter sperm development has recently been elucidated in
D. melanogaster
and
Aedes aegypti
mosquitoes, the Cifs’ extended impact on male reproductive fitness such as sperm morphology and quantity remains unclear. Here, using cytochemical, microscopic and transgenic assays in
D. melanogaster,
we demonstrate that both CifA and CifB cause a significant portion of defects in elongating spermatids, culminating in malformed mature sperm nuclei. Males expressing Cifs have reduced spermatid bundles and sperm counts, and transgenic expression of Cifs can occasionally result in no mature sperm formation. We reflect on Cifs’ varied functional impacts on the Host Modification model of CI as well as host evolution, behaviour and vector control strategies.
A Multiplex qPCR to Differentiate Monkeypox Virus Clades
Authors: Williams Christopher T. , Romero-Ramirez Alessandra , Semiu Adeleye Adesola , Ifabumuyi Samuel Oluwafunmbi , Gould Susan , Wooding Dominic , Allen Collette , Somasundaran Anushri , Mkpuma Nicodemus Nnabuike , Gado Dorcas , Adole Jolly Amoche , Amoo Abdulakeem Eniola , Adeyemi Abisola Ajoke , de Jarcy Laure Bosquillon , Goffinet Christine , Dunning Jake , Semple Malcolm G ,   ISARIC CCP UK investigators, Bahizire Esto , Akinpelu Afolabi , Fletcher Thomas E , Cubas-Atienzar Ana , Leggio Cristina , Adedeji Adeyinka , Omoare Adesuyi A. , Edwards Thomas
Published: February 2025

We designed a multiplex qPCR to differentiate monkeypox virus clades. In evaluations using clinical samples collected in the UK and Nigeria, the assay had an overall sensitivity of 78% (95% CI: 67.67% to 86.14%) and specificity of 94% (95% CI: 80.84% to 99.30%); for samples under Ct35 sensitivity was 98% (95% CI: 91.72% to 99.96%) and specificity was 94% (95% CI: 80.84% to 99.30%).
The NIH BRAIN Initiative's Experiment in Team Research
Authors: Bader Farah , David Karen K. , Lantz Crystal , Rangel-Gomez Mauricio , Gebrehiwet Hermon , Peng Grace C.Y. , Gnadt James
Published: February 2025

The NIH BRAIN Initiative is aimed at revolutionizing our understanding of the human brain. Presented here is an impact analysis of the BRAIN Initiative Team-Research BRAIN Circuits Program as an experiment in supporting team research in Neuroscience.
Serological evidence and factors associated to liver damage in malaria-typhoid infected patients consulting in two health facilities, Yaoundé-Cameroon
Authors: Essam Madeleine Yvanna Nyangono , Kouam Arnaud Fondjo , Fepa Armelle Gaelle Kwesseu , Seukep Armel Jackson , Zeuko’o Elisabeth Menkem , Somene Felicité Syntia Douanla , Nembo Nembu Erastus , Moundipa Paul Fewou , Njayou Frédéric Nico
Published: February 2025

Malaria and typhoid fever remain major health issues in developing countries like Cameroon, with frequent co-infections. The potential liver damage caused by their respective causative pathogens is overlooked in health management, posing a significant risk of severe liver injury and worsening patient conditions. Accordingly, this study investigated the risk factors associated to liver damage in febrile patients with malaria, typhoid fever, or co-infection at the Obili District Medical Center and Mvog-Betsi Dominican Hospital Center, Yaoundé, Cameroon. During 8 months, 350 febrile patients were evaluated for their adherence to preventive measures concerning malaria and typhoid fever using a structured questionnaire. Blood samples were analyzed forPlasmodiumspecies andSalmonellaantibodies and liver enzyme levels were measured. Liver damage was assessed employing the Roussel Uclaf Causality Assessment Method. Risk factors for infections and liver damage were identified using Fisher’s Exact and Chi-Square tests, with significance set at P<0.05. Among participants tested, 129 (36.86%) and 106 (30.29%) were positive for malaria and typhoid, respectively, while 56 (16.00%) were co-infected. Men (58/118 and 44/118) were more affected than women (71/232 and 62/232) for both malaria and typhoid. Participants aged between 20 and 40 years were the most affected by malaria (21.4%) and typhoid fever (17.4%). The non-use of mosquito nets, presence of standing water, bushes, and garbage dumps near residences were significant risk factors (Relative risk: RR>2.1; P<0.0001) for contracting malaria or typhoid fever. The co-infection status (Chi-2 = 18.30; P<0.0001), parasite density (Chi-2 = 9.8; P=0.0074), and delay before consulting (Chi-2 = 13.23; P=0.0013) were significant risk factors for the occurrence of liver injuries. Our findings demonstrated that the alteration of liver enzyme activities, reflecting liver damages among patients with malaria, typhoid, or malaria-typhoid co-infection, is a reality and should be considered during the patient’s treatment.
Cuffless Photoplethysmography Device for Continuous Monitoring of Blood Pressure
Authors: Hellou Elias , Jamal Tamer , Zuroff Elchanan , Kalhor Parvin , Delgado-Lelievre Maria , Lerman Lilach O. , Lerman Amir , Kachel Erez , Zoghby Ziad
Published: February 2025

Introduction

Accurate and convenient monitoring of BP is challenging and relies on cuff-based devices or in the postoperative and intensive care settings, on invasive measurements. The aim of this study was to prospectively evaluate the accuracy of BP measurements obtained from a novel, commercially available cuffless, non-invasive photoplethysmography (PPG)-based chest patch monitor compared to the reference standard invasive arterial pressure (IAP) monitoring, in patients after cardiac surgery.

Methods

This single center prospective study enrolled adults who underwent cardiac surgery. The PPG-based data were compared to IAP as part of standard of care. Bland-Altman plots and Pearson’s correlations were used to assess the accuracy between the two techniques.

Results

Ninety-six patients consented for the study. Mean age was 63.2±12.2 years (range 24 to 84), and 32 (33%) were women. Average monitoring time was 25.6±17.2. In total, we evaluated 78659 readings for systolic BP (SBP), 78818 for diastolic BP (DBP), and 92544 for HR analysis. These yielded correlation coefficients of r=0.959, 0.973, 0.966, and 0.962 for SBP, DBP, mean arterial pressure (MAP), and heart rate (HR), respectively. The Bland-Altman analysis showed a bias±SD of 0.1±4.8 mmHg for SBP; 0.4±2.1 mmHg for DBP; 0.26±2.6 mmHg for MAP, and 0.15±3.6 beats per minutes for HR. 95% of SBP, and 99.9% of DBP measurements were within 10 mmHg of the reference measurement.

Conclusion

Cuffless device offers a high level of accuracy of BP and HR, supporting the use of this novel noninvasive tool for continuous BP monitoring. Further studies are needed to validate those findings.
Combinatorial effects ofZingiber officinaleandCitrus limonjuices: Hypolipidemic and antioxidant insights fromin vivo,in vitro, andin silicoinvestigations
Authors: Bekkouch Oussama , Bekkouch Ayoub , Elbouny Hamza , Touiss Ilham , El Assri Soufiane , Choukri Mohammed , Bourhia Mohammed , Kim Kiryang , Kang Sojin , Choi Min , Choi Jinwon , Kim Hyo Jeong , Ahn Chi-Hoon , Park Moon Nyeo , Kim Bonglee , Amrani Souliman
Published: February 2025

The combined use ofZingiber officinale(ginger) andCitrus limon(lemon) has long been valued in traditional medicine for their significant therapeutic properties, particularly in supporting cardiovascular health. However, their synergistic effects on hyperlipidemia and oxidative stress, both critical risk factors for cardiovascular diseases, remain underexplored.

This study employed a multidisciplinary approach includingin vivo(mice model with triton WR-1339-induced hyperlipidemia),in vitro(antioxidant assays such as DPPH and ABTS), andin silico(molecular docking targeting HMG-CoA reductase) to evaluate the hypolipidemic and antioxidant potential of ginger and lemon juices. Phytochemical analysis identified high concentrations of bioactive compounds, with ginger juice containing 6-gingerol (15.54% peak area) and lemon juice featuring hesperidin (13.85% peak area) and rutin (5.57% peak area). These compounds were instrumental in the observed pharmacological effects.

The combined formulation significantly improved lipid profiles, reducing total cholesterol by 54.3%, triglycerides by 49.8%, and LDL by 58.1% while increasing HDL by 47.6% compared to hyperlipidemic controls (p < 0.05). Antioxidant assays revealed high free radical scavenging activity, with IC50values of 30.92 ± 2.00 µg/mL for ABTS and 44.94 ± 1.02 µg/mL for DPPH in the combined formulation. Molecular docking confirmed strong binding affinities, with hesperidin and 6-gingerol showing binding energies of -10.4 kcal/mol and -9.6 kcal/mol, respectively, against HMG-CoA reductase.

In conclusion, combiningZingiber officinaleandCitrus limonjuices demonstrates robust hypolipidemic and antioxidant effects, significantly outperforming the individual juices. These results support their potential as natural therapeutic agents for managing hyperlipidemia and oxidative stress. Further clinical studies are recommended to validate these promising findings and explore their application in nutraceutical development.
DeepSpot: Leveraging Spatial Context for Enhanced Spatial Transcriptomics Prediction from H&E Images
Authors: Nonchev Kalin , Dawo Sebastian , Silina Karina , Moch Holger , Andani Sonali ,   Tumor Profiler Consortium, Koelzer Viktor H , Rätsch Gunnar
Published: February 2025

Spatial transcriptomics technology remains resource-intensive and unlikely to be routinely adopted for patient care soon. This hinders the development of novel precision medicine solutions and, more importantly, limits the translation of research findings to patient treatment. Here, we present DeepSpot, a deep-set neural network that leverages recent foundation models in pathology and spatial multi-level tissue context to effectively predict spatial transcriptomics from H&E images. DeepSpot substantially improved gene correlations across multiple datasets from patients with metastatic melanoma, kidney, lung, or colon cancers as compared to previous state-of-the-art. Using DeepSpot, we generated 1 792 TCGA spatial transcriptomics samples (37 million spots) of the melanoma and renal cell cancer cohorts. We anticipate this to be a valuable resource for biological discovery and a benchmark for evaluating spatial transcriptomics models. We hope that DeepSpot and this dataset will stimulate further advancements in computational spatial transcriptomics analysis.
Probing Large Language Model Hidden States for Adverse Drug Reaction Knowledge
Authors: Berkowitz Jacob , Weissenbacher Davy , Srinivasan Apoorva , Friedrich Nadine A. , Acitores Cortina Jose Miguel , Kivelson Sophia , Hernandez Graciela Gonzalez , Tatonetti Nicholas P.
Published: February 2025

Large language models (LLMs) integrate knowledge from diverse sources into a single set of internal weights. However, these representations are difficult to interpret, complicating our understanding of the models’ learning capabilities. Sparse autoencoders (SAEs) linearize LLM embeddings, creating monosemantic features that both provide insight into the model’s comprehension and simplify downstream machine learning tasks. These features are especially important in biomedical applications where explainability is critical. Here, we evaluate the use of Gemma Scope SAEs to identify how LLMs store known facts involving adverse drug reactions (ADRs). We transform hidden-state embeddings of drug names from Gemma2-9b-it into interpretable features and train a linear classifier on these features to classify ADR likelihood, evaluating against an established benchmark. These embeddings provide strong predictive performance, giving AUC-ROC of 0.957 for identifying acute kidney injury, 0.902 for acute liver injury, 0.954 for acute myocardial infarction, and 0.963 for gastrointestinal bleeds. Notably, there are no significant differences (p > 0.05) in performance between the simple linear classifiers built on SAE outputs and neural networks trained on the raw embeddings, suggesting that the information lost in reconstruction is minima. This finding suggests that SAE-derived representations retain the essential information from the LLM while reducing model complexity, paving the way for more transparent, compute-efficient strategies. We believe that this approach can help synthesize the biomedical knowledge our models learn in training and be used for downstream applications, such as expanding reference sets for pharmacovigilance.
Evaluating Online Educational Resources for Osteogenesis Imperfecta: Insights from Google, Bing, and ChatGPT3.5
Authors: Partin Victoria-Jessica C. , Hooberman-Pineiro Andrea M. , Pace April A.
Published: February 2025

Background

Osteogenesis Imperfecta is a rare connective tissue disorder resulting in a diverse range of musculoskeletal deformities. Patient education is an important aspect of medical care, and the internet is a popular place in which patients seek information about their medical conditions. This is a cross-sectional study aimed to evaluate the quality of online patient educational websites about Osteogenesis Imperfecta.

Methods

The authors searched for patient education websites using Google and Bing. Twenty patient education websites about Osteogenesis Imperfecta were collected from each. Websites meeting inclusion criteria were evaluated using the DISCERN tool, JAMA Benchmark Criteria evaluation, and a Flesch-Kincaid Readability test. T-tests were used to compare search engine results. Websites were also collected from ChatGPT3.5, however, due to hallucinations and exclusion criteria, the sample size was too small to compare to the search engines.

Results

No significant differences were found between search engines, and the quality of the websites was not high. Average overall ratings for DISCERN were mediocre, and for the JAMA criteria they were low. The average readability scores required 8-9 grade level reading comprehension, although there was variability within each search engine.

Conclusion

Neither search engine provided significantly better sources than the other, the overall quality of the websites was not high, and the low readability scores could make these difficult for patients with lower health literacy to understand
Burden of rodent-borne viruses in rodents and zoonotic risk in human in Cambodia: a descriptive and observational study
Authors: Guillebaud Julia , Nouhin Janin , Hul Vibol , Hoem Thavry , Yanneth Oudamdaniel , Sim Mala , Khun Limmey , Phalla Y , Ken Sreymom , Pum Leakhena , Lim Reaksa , Meng Channa , Chhel Kimtuo , Nuon Sithun , Hoem Sreyleak , Nguon Kunthy , Chan Malen , Ly Sowath , Karlsson Erik A. , Reynes Jean-Marc , Sakunthabhai Anavaj , Dussart Philippe , Duong Veasna
Published: February 2025

Background

Rodent-borne viruses, including hantaviruses, arenaviruses, and rodent hepatitis virus (HEV-C), pose significant health threats to humans, causing severe diseases such as hepatitis, respiratory illness, and hemorrhagic fevers. In Cambodia, data on these viruses remain limited, and their burdens on human health are unknown. This study investigated the presences of these viruses in rodents and assessed potential human exposure across diverse environmental and socio-economic contexts in Cambodia.

Methods

The study was conducted in urban, semi-urban, and rural areas of Cambodia during the rainy (2020) and dry seasons (2022). Rodents were screened for arenavirus, hantavirus, and HEV-C using RT-PCR. Human serum samples from the same site were tested for IgG antibodies using ELISA. Factors associated with virus spillover into humans were analyzed.

Findings

Among 750 rodents, 9.7% carried at least one virus: 5.2% arenavirus, 3.3% hantavirus, and 1.9% HEV-C. Infection rates were highest in urban (14.5%), followed by semi-urban (11.9%) and rural (2.1%) interfaces. Arenavirus was more prevalent during the rainy season, while hantavirus and HEV-C remained consistent across seasons. Seroprevalence in human was 12.7% for arenavirus, 10.0% for hantavirus, and 24.2% for HEV. Higher arenavirus seroprevalence was associated with urban recidency and lower education level. Hantavirus seroprevalence was associated with urban residency, acute hepatitis history, and flood-prone living areas. HEV seroprevalence increased with urban residency, increasing age, and medical condition history.

Interpretation

Our findings highlighted the need for rodent control, improved market infrastructure, enhanced waste management, and public awareness on hygiene practices and zoonotic risks, especially in urban and high-risk areas.
Liquid-Dendrite Spiking Neural Network for Edge Devices: A 130 K-Parameter, 535 KB Model for Time-Domain Epileptic Seizure Detection
Authors: Herbozo Contreras Luis Fernando , Yu Leping , Huang Zhaojing , Nikpour Armin , Kavehei Omid
Published: February 2025

Epilepsy is a significant global health issue, requiring dependable diagnostic tools like scalp encephalogram (scalp-EEG), sub-scalp EEG, and intracranial EEG (iEEG) for precise seizure detection and treatment. AI has emerged as a powerful tool in this domain, offering the potential for real-time, responsive monitoring. Traditional methods often rely on feature extraction techniques like Short-Time Fourier Transform (STFT), which can increase power consumption, making them less suitable for deployment on edge devices. While large models can improve accuracy without STFT, their size also limits their practicality for edge applications. This study introduces Liquid-Dendrite, a novel bio-inspired model for seizure detection, leveraging Liquid-Time Constant Spiking Neurons (LTC-SN) and dendrites spiking neurons (dSN) with heterogeneous time-constants. The model comprises two hidden layers with dendritic neurons and one layer of liquid-time constant networks. Our model achieves a memory efficacy of 535 KB with 130 K trainable parameters. The model was tested across the most noteworthy epilepsy datasets for scalp EEG (TUH and CHB-MIT) and iEEG (EPILEPSIAE). Our model demonstrated commendable performance, achieving AUROC scores of 83%, 96%, and 93%, respectively, outperforming some existing models in an energy and memory-efficient way. Moreover, we conducted a robustness test by blacking out EEG channels at the inference stage, where we showed the ability of our network to work with fewer channels. We could deploy our tiny model and perform inference at the edge of the Raspberry Pi 5 without the need for additional quantization. This highlights the potential of Neuro-Inspired AI for efficient, small-scale, and energy-embedded AI systems across different brain modalities.
The range-resident logistic model: a new framework to formalize the population-dynamics consequences of range residency
Authors: Menezes Rafael , Calabrese Justin M. , Fagan William F. , Prado Paulo Inácio , Martinez-Garcia Ricardo
Published: February 2025

Individual movement is critical in shaping population dynamics. However, theoretical frame-works linking these two processes often make unrealistic assumptions about how animals move or, when attempting to incorporate realistic movement patterns, must rely on numerical simulations. To address this gap, we introduce the range-resident logistic model, which is an easy-to-simulate and mathematically tractable extension of the spatial logistic model that incorporates empirically supported range-resident movement. Our framework unifies previous non-spatial and (sessile) spatial formulations of the logistic model as limiting cases, recovering these two limits when home ranges are infinitely large and vanishingly small, respectively. Interpolating between these two regimes, the long-term population size depends nonlinearly on home-range size and spatial distribution. Neglecting range residency can hence lead to significantly under- or overestimating population carrying capacity. To better understand these results, we also introduce a novel crowding index that depends on movement parameters and can be estimated from tracking data. This index captures the influence of spatial structure on population size, and serves as a robust predictor of abundance. The range-resident logistic model is thus a unifying framework bridging movement and population ecology, and provides new insights into how different patterns of individual space usage shape intraspecific interactions and regulate population growth.
The Polymorphisms, Solvent Accessibility and Conservatism of Hepatitis C Virus Nonstructural 5B Protein
Authors: Lian Dejun
Published: February 2025

ABSTRACT

The polymorphisms of protein or protein family, that is, the divergences of amino acid and nucleotide sequences have provided much useful information on the divergent evolution of proteins. In this paper, we analyzed the polymorphisms of enzyme NS5B of HCV for which sequence variation among most isolates have been characterized and protein structures of the catalytic domain form of this enzyme are also known. For this protein, we found that solvent accessibility of residues in the protein structure is a strong predictor of whether or not an amino acid will be polymorphic and the residue variability. Apart from polymorphism, we found conservatism at every level among site is universal for this protein. We also found that purifying selection at different levels was strong in the forming of the polymorphisms and conservatism of this protein.
Dentate nucleus deep brain stimulation for spinocerebellar ataxia: results of a six-month follow-up
Authors: Zhao Liang , Qiu Chang , Dong Wenwen , Luo Bei , Sun Jian , Yan Jiuqi , Wei Xiang , Lu Guanghan , Liu Jingxuan , Zhang Wenbin
Published: February 2025

Spinocerebellar ataxia (SCA) is a genetically heterogeneous neurodegenerative disorder lacking effective treatments currently. While noninvasive cerebellum neuromodulation showed positive results, invasive techniques like deep brain stimulation (DBS) have not been fully assessed for SCA patients. This study evaluated the treatment outcomes of DBS targeting the cerebellar dentate nucleus (DN) in six SCA patients (SCA1, SCA3, SCA12) over a six-month follow-up. Bilateral DN-DBS leads were precisely implanted using a neurosurgical robot. The stimulation parameters, including current, frequency, and pulse width, were programmed iteratively at predefined intervals, and the improvements in ataxia symptoms were evaluated based on the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Current results showed that current amplitude was fundamental to ensuring therapeutic efficacy, while frequency differentially alleviated tremor with high-frequency stimulation and gait disorder at low frequencies. At the six-month follow-up, the SARA and ICARS scores decreased by 43% (8.17 ± 2.58 vs. 14.33 ± 1.51,p=0.014) and 51% (18.67 ± 7.50 vs. 38.17 ± 8.13,p=0.013) respectively compared with baseline. Our study demonstrated the promising therapeutic benefits of DN-DBS for SCA patients and provided preliminary experience for individualized parameter programming.
Human genetics suggests differing causal pathways fromHMGCRinhibition to coronary artery disease and type 2 diabetes
Authors: Hwang Seongwon , Karhunen Ville , Patel Ashish , Lockhart Sam , Carter Paul , Whittaker John , Burgess Stephen
Published: February 2025

Background

Statins lower low-density lipoprotein cholesterol (LDL-C) and reduce the risk of coronary artery disease (CAD). However, they also increase the risk of type 2 diabetes (T2D).

Methods

We consider genetic variants in the region of theHMGCRgene, which encodes the target of statins, and their associations with downstream consequences of statins. We use various statistical methods to identify causal pathways influencing CAD and T2D, and investigate whether these are the same or different for the two diseases.

Results

Colocalization analyses indicated that LDL-C and body mass index (BMI) have distinct genetic predictors in this gene region, suggesting that they do not lie on the same causal pathway. Multivariable Mendelian randomization analyses restricted to variants in theHMGCRgene region revealed LDL-C and BMI as causal risk factors for CAD, and BMI as a causal risk factor for T2D, but not LDL-C. A Bayesian model averaging method prioritized BMI as the most likely causal risk factor for T2D, and LDL-C as the second most likely causal risk factor for CAD (behind ubiquinone). Colocalization analyses provided consistent evidence of LDL-C colocalizing with CAD, and BMI colocalizing with T2D; evidence was inconsistent for colocalization of LDL-C with T2D, and BMI with CAD.

Conclusions

Our analyses suggest cardiovascular and metabolic consequences of statin usage are on different causal pathways, and hence could be influenced separately by targeted interventions. More broadly, our analysis workflow offers potential insights to identify pathway-specific causal risk factors that could provide possible repositioning or refinement opportunities for existing drug targets.

Key messages

We performed colocalization and cis-multivariable Mendelian randomization using genetic association data for variants in theHMGCRgene region to investigate causal pathways influencing coronary artery disease (CAD) and type 2 diabetes (T2D)

Our analyses suggest that the impact of HMGCR inhibition on CAD risk is mediated by both low-density lipoprotein cholesterol (LDL-C) and body mass index (BMI), whereas for T2D, risk was mediated via BMI but not LDL-C.

Our results suggest the possibility that targeted treatments could be developed to inhibit HMGCR in a more specific way that lowers CAD risk without increasing T2D risk.
Osteoporosis Prevalence in Cardiovascular Kidney Metabolic Syndrome: Implications for Mortality
Authors: Du Xi , Yang Qianyu , Duan Zhiqiang , Gu Hui , Zhang Xue , Liu Hao , Xiao Mao , Li Zhuoxing , Zhao Ming , Xiao Xiang
Published: February 2025

Objective

This study aims to investigate the prevalence of osteoporosis (OS) in patients with Cardiovascular Kidney Metabolic (CKM) Syndrome and its relationship with the risk of mortality in CKM patients.

Methods

Patients diagnosed with CKM were included from the National Health and Nutrition Examination Survey database between 2009 and 2018. The primary endpoint was all-cause mortality, while the secondary endpoint was cardiovascular mortality. The relationship between OS and the prognosis of all-cause mortality and cardiovascular mortality in CKM patients was assessed using Kaplan-Meier survival curves and multivariate Cox regression model.

Results

A total of 602 Non-CKM (stage 0) and 6129 CKM (stages 1, 2, 3, and 4) patients were included. The prevalence of OS in CKM patients at stages 0, 1, 2, 3, and 4 was 3.49%, 2.25%, 4.97%, 13.52%, and 8.39%, respectively. The multivariate Cox regression analysis revealed that compared to the normal bone mineral density group, CKM patients in the osteopenia group had a 55% increased risk of all-cause mortality (HR=1.55; 95% CI, 1.22-1.98,P= 0.001) and a 120% increase in the risk of cardiovascular mortality (HR=2.20; 95% CI, 1.39-3.46,P= 0.001); In the OS group, CKM patients exhibited a 199% increased risk of all-cause mortality (HR = 2.99; 95% CI, 1.86-4.82,P= 0.001) and a 2.14-fold increase in the risk of cardiovascular mortality (HR=3.14; 95% CI, 1.09-9.02,P= 0.03).

Conclusion

Osteopenia and OS are more prevalent in patients with CKM and are associated with an increased risk of all-cause and cardiovascular mortality.
Performance of DeepSeek-R1 in Ophthalmology: An Evaluation of Clinical Decision-Making and Cost-Effectiveness
Authors: Mikhail David , Farah Andrew , Milad Jason , Nassrallah Wissam , Mihalache Andrew , Milad Daniel , Antaki Fares , Balas Michael , Popovic Marko M. , Feo Alessandro , Muni Rajeev H. , Keane Pearse A. , Duval Renaud
Published: February 2025

Purpose

To compare the performance and cost-effectiveness of DeepSeek-R1 with OpenAI o1 in diagnosing and managing ophthalmology clinical cases.

Study Design

Cross-sectional evaluation.

Methods

A total of 300 clinical cases spanning 10 different ophthalmology subspecialties were collected from StatPearls. Each case presented a multiple-choice question regarding the diagnosis or management of the clinical case. DeepSeek-R1 was accessed through its public chat-based interface, while OpenAI o1 was queried via an Application Program Interface (API) with a standardized temperature setting of 0.3. Both models were prompted using the Plan-and-Solve+ (PS+) prompt engineering method, instructing them to answer multiple choice questions for each case. Performance was calculated as the proportion of correctly answered multiple choice questions. McNemar’s test was employed to compare the two models’ performance on paired data. Inter-model agreement for correct diagnoses was evaluated via Cohen’s kappa. A token-based cost analysis was performed to estimate the comparative expenditures of running each model at scale, accounting for both input prompts and model-generated output.

Results

DeepSeek-R1 and OpenAI o1 both achieved an identical overall performance of 82.0% (n=246/300; 95% CI: 77.3-85.9). Subspeciality-specific analysis revealed numerical variation in performance, though none of these comparisons reached statistical significance (p>0.05).

Agreement in performance between the models was moderate overall (κ=0.503, p<0.001), with substantial agreement in Refractive Management/Intervention (κ=0.698, p<0.001) and moderate agreement in Retina/Vitreous (κ=0.561, p<0.001) and Ocular Pathology/Oncology (κ=0.495, p<0.01) cases. Cost analysis indicated an approximately 15-fold reduction in per-query, token-related expenses when using DeepSeek-R1 compared with OpenAI o1 for the same workload.

Conclusions

DeepSeek-R1 demonstrates robust diagnostic reasoning and management decision-making capabilities, performing comparably to OpenAI o1 across a range of ophthalmic subspecialty cases, while also offering a substantial reduction in usage costs. These findings highlight the feasibility of utilizing open-weight, reinforcement learning-augmented LLMs as an accessible, cost-effective alternative to proprietary models.