bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a low budget planeterella for auroral outreach incorporating physics student co-creation principles
Authors: Whittaker Ian C , Elkan Ethan , Toms Ryan
Published: December 2024

A planeterella (an auroral simulator) has been built at Nottingham Trent University within the cost of a student postgraduate Masters project budget (£100). This instrument is currently only the third working planeterella in the UK, and while not as sophisticated as it’s two older cousins, it still demonstrates the space physics principles at the same time as providing an educational and inspirational benefit. The final equipment has proved successful in engaging students, stakeholders, and the public with ‘seeing’ magnetic fields and auroral processes. The build requirements and method are provided to allow other higher education institutions to be able to create their own planeterella as scientific demonstrations and student projects; only requiring small budgets and common equipment borrowed from physics teaching and research laboratories.
Motherhood Penalty—Beyond Bias? From Stereotypes to Substitutability Structures
Authors: Halrynjo Sigtona , Mangset Marte
Published: December 2024

Mothers continue to experience lower wages and slower career progression than fathers. Are mothers penalized due to prejudice or due to the costs of family-friendly work conditions? Our review of experimental studies on motherhood bias reveals a paradox: implicit bias against mothers is evident in many US and European studies, but absent in Scandinavian experimental studies; yet, mothers still face a wage and career gap. We revisit explanations related to social structures and gendered work–family specialization, including Goldin’s theory of exponential rewards for time and availability. By reviewing longitudinal Scandinavian studies and exploring the role of individual competition in particular job markets, we offer a nuanced understanding of flexibility and substitutability. Finally, we outline a shift in the theoretical lens for examining and challenging the wage and career gap—from stereotypes to substitutability structures—and introduce a model predicting the relation between individualized versus collective substitutability structures and the degree of individual and/or gendered costs.
Inorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway
Authors: Du Kunyu , Shu Jingkui , Wu Jintao , Liu Na , Ma He , Jiang Jinyun , He Yuefeng , Wu Xinan
Published: December 2024

This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA). The results showed that silencing AGO2 not only reduced cell viability but also intensified apoptosis, highlighting its role in activating the p53 pathway. This was further supported by increased phosphorylation of p53 at Ser392 and Thr55, reinforcing AGO2’s involvement in apoptotic processes. The study underscores the potential of AGO2 as a therapeutic target in arsenic-related pathologies and highlights the critical need for managing occupational exposure to arsenic.
Anti-M2-pyruvate kinase autoantibodies are correlated with digestive damage in human Chagas disease
Authors: da Silva Denis Dantas , Pereira Nathalie de Sena , Nunes Daniela Ferreira , Brito Ramayana Morais de Medeiros , Pereira Luanderson Cardoso , da Silva Andressa Noronha Barbosa , Brito Carlos Ramon do Nascimento , Andrade Cléber de Mesquita , Galvão Lúcia Maria da Cunha , da Câmara Antonia Claudia Jácome , Nascimento Manuela Sales Lima , Guedes Paulo Marcos Matta
Published: December 2024

Background

Determining esophageal and colon involvement in patients with Chagas disease occurs through invasive and uncomfortable examinations, which in most cases are not performed. The objective of this study was to assess the involvement of anti-M2-pyruvate kinase (M2-PK) autoantibodies in the development of digestive alterations and/or in the diagnosis of the digestive form of human Chagas disease.

Methods

The total IgG and isotype (IgG1, IgG2, IgG3, IgG4) production was quantified using the antigen of Trypanosoma cruzi and the human M2-PK recombinant protein via the ELISA technique. The tests were conducted with serum samples from patients with indeterminate, cardiac, digestive and cardiodigestive clinical forms of Chagas disease, and the results were correlated with the dilatation degree of the esophagus and colon.

Results

Patients with the digestive form of Chagas disease had higher IgG4 anti-M2-PK autoantibody production compared with patients with the indeterminate and cardiac forms and the healthy control group. Furthermore, a positive correlation was observed between sigmoid and rectum size with IgG4 anti-M2-PK autoantibody production.

Conclusions

These results demonstrate that IgG4 anti-M2-PK autoantibodies correlate with digestive damage in human Chagas disease, and their presence may also be implicated in the development of digestive lesions.
Application and development prospect of digital twin in the forensic identification of cardiovascular diseases
Authors: Huang Lei , Pan Lei , Wu Chaojun , Tian Minglang , Li Qi , Peng Yao , Li Qiyu , Li Ying
Published: December 2024

The precise and prompt identification of cardiovascular diseases holds utmost significance in judicial justice. However, owing to their intricate pathogenesis and clinical manifestations, cardiovascular ailments have persistently posed a challenge in forensic identification. Determining the correlation between injuries, cause of death, and the underlying disease during forensic investigations is particularly arduous. Traditional forensic autopsy and virtual anatomy, while offering a certain degree of evidentiary support, still face limitations in accurately assessing the relationship between injuries, cause of death, and specific cardiovascular conditions. Enter digital twin—an advanced technological solution that has exhibited immense potential across various domains. This paper delves into the utilization of digital twin in the forensic identification of cardiovascular diseases. Furthermore, it explores the potential impact and future prospects of digital twin in enhancing identification accuracy, propelling the advancement of forensic medicine, and fostering overall medical progress.
T-stage diagnosis of lung cancer based on deep learning in CT images
Authors: Fan Rutao , Chen Jincheng , Xu Shanshan , Wu Wei , Yi Jian , Zhang Nuoyu , Chang Miaoyi , Dong Xuanxuan , Chen Xizhu , Zou Yuxin , Li Xinwei , Wu Yi
Published: December 2024

Objective:

To explore the advantages of Swin-Transformer (SwinT) network in T-staging diagnosis of lung cancer computed tomography (CT) images by comparing it with Res-Net, Vgg-Net, and Mobile-Net networks.

Methods:

CT images of a total of 176 patients with lung cancer confirmed by pathological biopsy were collected from the First Affiliated Hospital of Army Medical University between 2021 and 2023. Based on the patients’ pathological T-staging reports, the patients’ images were classified into 4 categories: T1, T2, T3, and T4, and all the patients were simply randomly divided into a training set (n = 123), a validation set (n = 18), and a test set (n = 35) in the ratio of 7∶1∶2 for training the intelligent T-staging diagnostic model, which was used for training the intelligent T-staging diagnostic model by using the accuracy, precision, confusion matrix, recall rate, F1 score (F1- Score), receiver operating haracteristic (ROC) curve, and area under the ROC curve (AUC) parameters to assess the diagnostic efficacy of the network.

Results:

In the four classifications of T1, T2, T3, and T4, the accuracy in the training set of Res-Net, Vgg-Net, Mobile-Net, and SwinT network models were 0.5278, 0.6111, 0.6389, and 0.7222, as well as the AUC was 0.7275, 0.7850, 0.7275, and 0.8650.the SwinT network model had the best combined results.

Conclusion:

Compared with Res-Net, Vgg-Net and Mobile-Net networks, SwinT network achieves the optimal prediction performance in the lung cancer CT image classification task, and can be used for the smart T-staging of lung cancer to be able to diagnose, to improve the diagnosis and treatment efficiency, to shorten the diagnosis time, and to save medical resources.
Comparable results for the Femoral Neck System and three-screw fixation in femoral neck fracture treatment
Authors: Honkanen Jukka , Forsbacka Nora , Strengell Ida , Laaksonen Inari , Mäkelä Keijo , Koivisto Mari , Huovinen Ville , Ekman Elina
Published: December 2024

Objectives:

To report outcomes of femoral neck fractures (FNFs) treated with Femoral Neck System (FNS) and to compare the risks of later conversion to arthroplasty for FNS and fixation with cannulated screws (CNSs).

Design:

A retrospective study.

Setting:

A single-center study (Turku University Hospital, Finland).

Patients:

Data on 51 patients with FNFs treated with FNS between January 1, 2019, and May 31, 2021, were retrospectively reviewed. In addition, data on 301 patients treated with cannulated screws were collected and analyzed in a previous study.

Intervention:

Patients with FNFs underwent osteosynthesis with FNS.

Main Outcome Measurements:

Patients' preoperative and postoperative radiographs were analyzed and measured to determine preoperative displacement, preoperative posterior tilt, and quality of reduction. Later conversion to arthroplasty and other reoperations were recorded. The risk of later conversion to arthroplasty was compared between the FNS group and CNS group.

Results:

The overall reoperation rate in the FNS group was 20%, and 16% of the patients treated with FNS underwent later conversion to arthroplasty. In the multivariate analysis, age, sex, and fracture displacement were not associated with increased risk of later conversion to arthroplasty. In comparison with fixation with cannulated screws, there was no statistically significant difference in the probability of later conversion to arthroplasty between the groups.

Conclusion:

FNS seems to have a comparable reoperation rate and conversion-to-arthroplasty rate compared with the gold standard treatment.

Level of Evidence:

III.
Toward Digital Twins in the Intensive Care Unit: A Medication Management Case Study
Authors: Eslami Behnaz , Afshar Majid , Tootooni M. Samie , Miller Timothy , Churpek Matthew , Gao Yanjun , Dligach Dmitriy
Published: December 2024

Digital twins, computational representations of individuals or systems, offer promising applications in the intensive care unit (ICU) by enhancing decision-making and reducing cognitive load. We developed digital twins using a large language model (LLM), LLaMA-3, fine-tuned with Low-Rank Adapters (LoRA) on physician notes from different ICU specialties in the MIMIC-III dataset. This study hypothesizes that specialty-specific training improves treatment recommendation accuracy compared to training on other ICU specialties. Additionally, we evaluated a zero-shot baseline model, which relied solely on contextual instructions without training. Discharge summaries were analyzed, and medications were masked to create datasets for model training and testing. The medical ICU dataset (1,000 notes) was used for evaluation, and performance was measured using BERTScore and ROUGE-L. LLMs trained on medical ICU notes achieved the highest BERTScore (0.842), outperforming models trained on other specialties or mixed datasets, while untrained zero-shot models showed the lowest performance. These results underscore the value of context-specific training for digital twins, offering foundational insights into LLMs for personalized clinical decision support.
A population model of age and gender specific cardiac troponin levels
Authors: Corlan Alexandru Dan
Published: December 2024

The range of the high-sensitivity cardiac troponin (HSCTN) values in the gen-eral population increases progressively with age, being several times higher in older patients, beyond 70 years old, than in younger ones, below 40.

More accurate normal limits for HSCTN, taking into account age and gender, are needed for the differential diagnosis and evaluation of the prognostic signif-icance of increases that do not reach the vendor-supplied upper reference limits (URL).

We performed an analysis of the high sensitivity cardiac troponin (HSCTN) of 21743 individuals, representative for the general US population, that were studied in the NHANES survey performed by the Center for Disease Control of the USA. The vendor supplied URL values are typically several times higher than the actual upper limit in subjects under 40 and correspond to the URL at ages between 51 and 84 for specific vendors and genders.

For each HSCTN test variant, we considered each one year age group between 1 and 85 and either gender. The distribution of the logarithmed HSCTN for a given test variant and gender, in each subsamplei, is relatively close to Gaussian (N (µi, σi)). Two quadratic models, for the 1–15 and the 16–85 age ranges, were found to fit well with theµi, while theσifollow a linear model. These theoretical distributions can be used used to estimate any quantiles of the HSCTN distribution as functions of age and gender, including the upper reference limit (URL) for the HSCTN I and T in the general population.

Consequently, it is possible to construct a calculated HSCTN indicator that represents the estimated age and gender specific centile in which a measurement with a specific test kit falls, or the percentual distance above the 99th centile. This indicator would be independent of age, gender and kit-vendor, and thus more accurate and easier to employ in clinical practice.
Dorsolateral prefrontal cortex TMS evokes responses in the subgenual anterior cingulate cortex: Evidence from human intracranial EEG
Authors: Trapp Nicholas T. , Liu Xianqing , Li Zhuoran , Bruss Joel , Keller Corey J. , Boes Aaron D. , Jiang Jing
Published: December 2024

Transcranial magnetic stimulation combined with intracranial local field potential recordings in humans (TMS-iEEG) represents a new method for investigating electrophysiologic effects of TMS with spatiotemporal precision. We applied TMS-iEEG to the dorsolateral prefrontal cortex (dlPFC) in two subjects and demonstrate evoked activity in the subgenual anterior cingulate cortex (sgACC). This study provides direct electrophysiologic evidence that dlPFC TMS, as targeted for depression treatment, can modulate brain activity in the sgACC.
Primary healthcare capacity in Northwest Ethiopia: Insights through the Primary health care progression model
Authors: Tsehay Chalie Tadie , Worku Nigusu , Dellie Endalkachew , Negash Wubshet Debebe , Aschalew Andualem Yalew , Debie Ayal , Haile Tsegaye G. , Fetene Samrawit Mihret , Kebede Adane , Atnafu Asmamaw
Published: December 2024

Background

Primary healthcare (PHC) systems are widely recognized as essential foundations for ensuring equitable access to quality medical care for all. Achieving the health-related Sustainable Development Goals (SDGs), including the sub-targets of universal health coverage by 2030 requires resilient PHC systems, supported by scientific evidences to inform better policy. However, there is a lack of evidence regarding the PHC system capacity at the operational level in Ethiopia. Therefore, we assessed the capacity of primary health care at the health facilities level in northwest Ethiopia.

Methods

We used a mixed-method assessment of the PHC capacity guided by the progression model, which includes governance, input, and population health and facility management domains with a total of 33 rubric-based (scaled from 1 to 4) measurement items. We included a total of three primary hospitals and five health centers from Northwest Ethiopia. Key informants interviews, facility observations including guideline and policy reviews and reports, discussion with key stakeholders, were our source of data. Data were independently collected by two groups of assessors (internal and external assessors) and a final score was determined by consensus through panel discussion. Finally, we summarized and synthesized the results over the three domains of PHC capacity assessment and the nine subdomains.

Results

All the three domains scores were found to be low. We found that the scores were 1.5, 2.2, and 1.3 out of four points for the governance, input, and population health and facility management domains, respectively. While we found a better achievement on health management information system and civil registration and vital statistics, the local priority setting, facility management capability, innovation and learning, community engagement and social accountability measures had lowest capacity score.

Conclusions

Our study highlighted that the governance and population health and facility management domains scored lower at the health facilities in central Gondar zone. Therefore, it is crucial to enhance these domains to strengthen PHC though a comprehensive approach, aiming to meet its targets and achieve UHC by 2030 or beyond.
Neurocognitive Outcome after Pediatric Traumatic Brain Injury: Patient Subgroups with Diverging Outcome
Authors: Kooper C.C. , Königs M. , Steenweg M.E. , Hunfeld M. , Scheurer C.D. , Schippers H.M. , Peper W. , Popma A. , van Woensel J.B.M. , Buis D.R. , Bruining H. , Engelen M. , Oosterlaan J.
Published: December 2024

Background and Objectives

Traumatic brain injury (TBI) is the leading cause of acquired disability in children. Children with TBI are at risk of persistent deficits in neurocognitive functioning that affect daily life. However, neurocognitive outcomes are highly heterogenous and this heterogeneity is poorly understood. This study aims to investigate whether the heterogeneity in neurocognitive outcome can be reduced by distinguishing subgroups of children with distinct profiles of neurocognitive functioning, and to investigate whether these subgroups differ in demographic, premorbid and clinical characteristics.

Methods

This multicenter study included a consecutive cohort of children with mild to severe TBI and demographically matched neurologically healthy (NH) children. Seven neurocognitive domains were assessed six months post-TBI using computerized tests. The TBI and NH group were compared on the neurocognitive domains using t-tests. Results of the TBI group were subjected to cluster analysis to derive subgroups with distinct profiles of neurocognitive functioning. Resulting subgroups were compared on demographic, premorbid and clinical characteristics available at time of hospital visit.

Results

A total of 113 children with TBI and 113 NH children were included. The TBI group had lower performance than NH children on the neurocognitive domains Speed, Stability, Attention & Control, Verbal Working Memory and Visual Working Memory (.009≤ps≤.047, -.42≤ds≤-.29). Cluster analysis revealed four subgroups of patients with diverging neurocognitive outcome profiles. One subgroup was characterized by good outcome, whereas three subgroups had adverse outcome characterized by weak global outcome, weak visual-processing outcome or weak executive functioning outcome. The subgroups did not differ in clinical characteristics but did differ in demographic and premorbid characteristics. The weak global outcome subgroup had more premorbid behavioral problems, while the good outcome subgroup had higher socio-economic status than the other subgroups.

Discussion

This study indicates that children with mild to severe TBI exhibit neurocognitive deficits compared to matched controls at six months post TBI, among which subgroups of children with distinct neurocognitive outcome profiles exist. The neurocognitive outcome subgroups represent children with diverging severity and configuration of neurocognitive weaknesses. The subgroups with the diverging neurocognitive outcome profiles did not differ in clinical characteristics, highlighting the importance to consider other factors for the prognosis of neurocognitive outcome.
Comparing tangible retinal image characteristics with deep learning features reveals their complementarity for gene association and disease prediction
Authors: Beyeler Michael J , Trofimova Olga , Bontempi Dennis , Böttger Leah , Bors Sacha , Iuliani Ilaria , Vela Sofia Ortin , Presby David M , Bergmann Sven
Published: December 2024

Advances in computer-aided analyses, including deep learning (DL), are transforming medical imaging by enabling automated disease risk predictions and aiding clinical interpretation. However, DL’s outputs and latent variables (LVs) often lack interpretability, impeding clinical trust and biological insight. In this study, we evaluatedRETFound, a foundation model for retinal images, using a dataset annotated with clinically interpretable tangible image features (TIFs). Our findings revealed that individual LVs poorly represent complex TIFs but achieve higher accuracy when combined linearly. Fine-tuningRETFoundto predict TIFs, providing “deep TIFs” provided better, but far from perfect surrogates, highlighting the limitations of DL approaches to fully characterise retinal images. Yet, our genetic analyses showed that deep TIFs exhibit heritability comparable to or exceeding measured TIFs but highlighted non-genetic variability in LVs. While measured and deep TIFs, as well as LVs, showed overlapping genetic and disease associations, their complementarity enhances prediction models. Notably, deep TIFs excelled in ocular disease prediction, emphasising their potential to refine retinal diagnostics and bridge gaps in conventional assessments of vascular morphology.
Effect of acupuncture on anxious symptoms in healthcare students with generalized anxiety disorder: A protocol for a randomized controlled clinical trial
Authors: da Silva Cláudio Calixto Carlos , Matos Marcos André de , Batista Sandro Rogério Rodrigues
Published: December 2024

Background

The present study aimed to investigate the effect of acupuncture on generalized anxiety disorder (GAD) in healthcare students. On the basis of increasing prevalence of anxiety disorders in this population and the research gap regarding the use of acupuncture as a therapeutic intervention, this study aims to fill this gap and provide solid evidence on the effectiveness and safety of this practice.

Methods

The methodology will include a single-center, single-blinded, randomized, placebo-controlled clinical trial. A total of 87 patients diagnosed with generalized anxiety disorder will be enlisted and randomized to either manual acupuncture or sham acupuncture. Participants in both arms will undergo 30 minute-sessions once weekly until 10 sessions are completed over 4 months. The primary outcome measure will be assessed via 3 scales validated for Brazil: Generalized Anxiety Disorder Scale (GAD-7), The Beck Anxiety Inventory (BECK-A), The Penn State Worry Questionnaire (PSWQ) at baseline, 5 weeks and 10 weeks. All adverse events will be meticulously recorded and categorized by their time of onset and resolution, with appropriate clinical assessments provided for each patient.

Discussion

Acupuncture is expected to significantly reduce anxiety symptoms in participants. The results of this study will contribute to the evidence on the effectiveness and safety of acupuncture in treating anxiety in healthcare students, providing data that may influence clinical practices and future treatment guidelines.

Trial Registration

The Brazilian Registry of Clinical Trials:RBR-9stskc6. Registered 4 December 2024
THE DYNAMIC AFFECT RECOGNITION TEST: CONSTRUCTION AND VALIDATION IN NEURODEGENERATIVE SYNDROMES
Authors: Rankin Katherine P. , Ulugut Hulya , Radke Anneliese , Grossman Scott , Poorzand Pardis , Shany-Ur Tal , Kramer Joel H. , Possin Katherine L. , Sturm Virginia E. , Gorno Tempini Maria Luisa , Miller Bruce L.
Published: December 2024

Learning objective

To validate a novel video-based emotion identification measure in persons with neurodegeneration and show correspondence to emotion-relevant brain systems

Background

Given advances in disease-modifying therapies for dementia, the dementia field needs objective, practical behavioral assessment tools for patient trial selection and monitoring. The Dynamic Affect Recognition Test (DART) was designed to remedy limitations of instruments typically used to measure emotion identification deficits in persons with dementia (PWD).

Method

Participants included 372 individuals, including 257 early stage PWD (Clinical Dementia Rating ≤1, Mini-Mental State Examination ≥20; 66 behavioral variant frontotemporal dementia [bvFTD], 27 semantic variant primary progressive aphasia [svPPA], 23 semantic bvFTD [sbvFTD], 33 non-fluent PPA [nfvPPA], 26 progressive supranuclear palsy [PSP], 28 corticobasal syndrome [CBS], 42 Alzheimer’s disease [AD], 12 logopenic variant PPA [lvPPA]), and 115 healthy controls (HC), watched 12 15-second videos of an actor expressing a basic emotion (happy, surprised, sad, angry, fearful, disgusted) via congruent facial/vocal/postural cues, with semantically neutral scripts. Participants selected the emotion from a randomized visual array. Voxel-based morphometry (VBM) analysis was performed to show brain structure correlates of DART, controlling for non-emotional naming ability (Boston Naming Test, BNT).

Results

DART performance was worse in PWD than older HC (p<0.001), with the lowest scores observed in the sbvFTD group. A DART 10 cut-off score differentiates PWD from HC with a 90% sensitivity and 49% specificity (AUC=82%). A DART 9/12 score yielded 93% sensitivity/67% specificity (AUC=87%) for discriminating social cognition disorders from HC, while a 7/12 score differentiated sbvFTD from HC with 100% sensitivity/93% specificity (AUC=97%). VBM showed poorer DART performance significantly predicts focal brain volume loss in right-sided emotion processing areas including insula, temporal pole, caudate, superior frontal gyrus and supplementary motor cortex (pFWE<0.05).

Conclusions

The DART is a brief, psychometrically robust video-based test of emotion reading (i) designed to be practically useful in realistic assessment settings, (ii) effectively reveals emotion identification impairments in PWD, (iii) shows specificity for identifying PWD exhibiting real-life SCDs (i.e. bvFTD, svPPA, sbvFTD), (iv) corresponds to the expected structural anatomy of emotion reading, and (v) is freely available to researchers and clinicians.
The association between enlarged perivascular spaces and muscle sympathetic nerve activity in normotensive and hypertensive humans
Authors: Rim Donggyu , Pham William , Fatouleh Rania , Hennessy Annemarie , Schlaich Markus , Henderson Luke A , Macefield Vaughan G
Published: December 2024

Background

Perivascular spaces (PVS) are fluid-filled spaces that functions as channels for glymphatic clearance in the brain. Enlarged perivascular spaces (ePVS) have been associated with high blood pressure. Hypertension features abnormal increases in muscle sympathetic nerve activity (MSNA), which constricts blood vessels in the muscle vascular bed, but the underlying mechanisms for this increase are not understood. Moreover, the association between ePVS and the resting sympathetic outflow from the brain has not been studied in normotensive or hypertensive humans. Therefore, we assessed whether ePVS is associated with muscle sympathetic nerve activity (MSNA) in 25 hypertensive patients and 50 healthy normotensive adults.

Methods

T1-weighted MRI anatomical brain images were analysed for ePVS using a deep learning-based segmentation algorithm – nnU-Net. ePVS in the white matter (WM), basal ganglia (BG), hippocampus (HP), and midbrain (MB) were analysed. Spontaneous bursts of MSNA were recorded from the right common peroneal nerve via a tungsten microelectrode immediately before the MRI scan.

Results

Significant associations were found between ePVS and MSNA in the WM, BG, and HP in both the normotensive and hypertensive groups after adjusting for confounding factors (age, sex, mean blood pressure, total intracranial volume). However, the association between MSNA and MB ePVS was only observed in the hypertensive group.

Conclusion

This finding provides insights into the pathophysiology of elevated sympathetic drive in hypertension.

What is new?

• Enlarged perivascular spaces (ePVS) are associated with muscle sympathetic nerve activity (MSNA) in normotensive and hypertensive humans.

• Hypertensives and normotensives display differences in the association between the midbrain ePVS and MSNA.

What are the clinical implications?

• Insights into the centrally driven pathophysiological mechanism of elevated sympathetic nerve outflow in hypertension has been revealed.

• ePVS may be used as an imaging biomarker for individuals with high sympathetic nerve activity, allowing identification of risk individuals that require microneurographic assessment of sympathetic nerve activity
The epidemiology and clinical features of HIV andTrypanosoma cruzi(Chagas disease) co-infection: A systematic review and individual patient data analysis
Authors: Elkheir Natalie , Carter Jessica , Dominic Catherine , Lok Pat , Fisayo Temitope , Michelen Melina , De Barros Barbara , Goldsmith Jaimie Wilson , Butler Michael , Price Amy , Mehotra Anushka , Nabarro Laura , Ahmed Nadia , Chiodini Peter , Moore David A.J.
Published: December 2024

Background

Narrative descriptions of HIV andTrypanosoma cruzi,the causative agent of Chagas disease, co-infection exist in the literature but the breadth and depth of the data underlying these descriptions has not been previously thoroughly scrutinised and reactivation is poorly understood. The aim of this systematic review was to identify, synthesise and analyse the published literature on the epidemiology and clinical features ofT. cruziand HIV co-infection.

Methods

A systematic review of published literature on HIV andT. cruzico-infection was conducted. Six international databases were searched: Medline, Embase, Global Health, Global Index Medicus, Web of Science and Scopus. Articles reporting on HIV andTrypanosoma cruzico-infection, as defined by the authors, with no restrictions on study type, language or date of publication or reporting were included.

Results

152 articles (62% case reports or series) were included which reported on 1,603 individuals with co-infection and 225 with presumed reactivation. Reported prevalence of co-infection varied greatly by region and setting of screening, from 0.1 to 1% in unselected populations, and was particularly high when screening inpatients known to have HIV forT. cruziinfection (26-48%). 83% of reactivations were reported in individuals with CD4<200 cells/mm3. CNS reactivation, typically presenting with meningoencephalitis and/or cerebral lesions, accounted for 68% of all published cases of reactivation. Myocarditis (accounting for 9% published reactivation cases) was less well characterised. Mortality of all reactivation cases was 59% (77% in those with CNS reactivation).

Conclusion

T. cruzireactivation mainly affects those with untreated HIV and lower CD4 counts. CNS reactivation is the most common clinical picture and confers high mortality. Prompt recognition of reactivation and immediate initiation of trypanocidal therapy (with benznidazole or nifurtimox) is recommended. Increased education and better awareness of the risks of co-infection are needed, as is systematic screening of individuals at-risk.
Enhancing Semantic Interoperability in Precision Medicine: Converting OMOP CDM to Beacon v2 in the Spanish IMPaCT-Data Project
Authors: Rueda Manuel , Ramírez-Anguita Juan Manuel , López-Sánchez Victoria , Aguiló-Castillo Sergi , Gas López Maria Eugenia , Labarga Alberto , Mayer Miguel-Ángel , Ripoll Esteve Javier , Gut Ivo G.
Published: December 2024

Objective

To introduce novel methods to convert OMOP CDM data into GA4GH Beacon v2 format, enhancing semantic interoperability within Spain’s IMPaCT-Data program for personalized medicine.

Materials and Methods

We utilized a file-based approach with the Convert-Pheno tool to transform OMOP CDM exports into Beacon v2 format. Additionally, we developed a direct connection from PostgreSQL OMOP CDM to the Beacon v2 API, enabling real-time data access without intermediary text files.

Results

We successfully converted OMOP CDM datasets from three research centers (CNAG, IIS La Fe, and HMar) to Beacon v2 format with nearly 100% data completeness. The direct connection approach improved data freshness and adaptability for dynamic environments.

Discussion and Conclusion

This study introduces two methodologies for integrating OMOP CDM data with Beacon v2, offering performance optimization or real-time access. These methodologies can be adopted by other centers to enhance interoperability and collaboration in health data sharing.
Refining LLMs Outputs with Iterative Consensus Ensemble (ICE)
Authors: Omar Mahmud , Glicksberg Benjamin S , Nadkarni Girish N , Klang Eyal
Published: December 2024

Large language models (LLMs) show promising accuracy on challenging tasks, including medical question answering. Yet, direct gains from model upgrades can plateau, and reliability issues persist. We introduce Iterative Consensus Ensemble (ICE), a proof-of-concept framework that refines answers through iterative reasoning and feedback among multiple LLMs. This ensemble method encourages diverse models to scrutinize each other’s outputs, converging on a consensus solution. We tested ICE on four different datasets. These included over 4,000 multiple-choice questions drawn from a newly curated primary care exam set, established medical benchmarks, and a PhD-level reasoning dataset. Compared to initial single-model attempts, ICE improved final overall accuracy by up to 27%. It reached accuracies 81% in medical subsets and 72% in multi-domain tasks from initial scores of about 72% and 60%, respectively. In a particularly challenging PhD-level reasoning benchmark (GPQA-diamond), ICE raised performance from 46.9% initially to 68.2% at the final consensus, a relative gain exceeding 45%. On a specialized family medicine dataset, ICE’s results were statistically indistinguishable from those of a complex reasoning model (O1-preview), despite O1’s higher cost and computational demands. Additional analyses showed that ICE’s iterative consensus remained effective under different prompting styles. Our proposed framework leverages standard LLMs and repeated prompting, requiring no specialized reward models or intricate token-level fusion. These findings show that iterative collaboration can transform LLM ensembles into more reliable, cost-efficient solvers, advancing performance in medical and general reasoning domains. Future refinements may integrate chain-of-thought steps or specialist models, extending this approach to more complex challenges as LLMs and benchmarks continue to evolve.
Construction and Analysis of Risk Model of Postoperative Stone Recurrence in Patients with Cholelithiasis: A Protocol-Based KAP Questionnaire Approach
Authors: Xie Hui , Hao Fatao , Meng Yong , Du Lin , Wang Xiangyu
Published: December 2024

Background

Patients who undertake endoscopic stone removal had a chance to have CBDS recurrence, which can lead to many severe complication. Many risk factors cause the recurrence of CBDS, but many factors cannot be controlled by clinical intervention. As for the patients in daily life, healthy lifestyle is important to prevent the recurrence of CBDS. The questionnaire of KAP can collect the real information about patients and guide the clinical work.

Methods

100 CBDS recurrence patients after surgery in our hospital were enrolled. A pair of self-designed questionnaires on KAP were used to collect data and assess the KAP towards CBDS recurrence.

Results

The mean score for KAP of CBDS recurrence patients was 30.29±2.87, 26.42±±3.53 and 27.23±±3.48. Pearson correlation analysis showed that knowledge aspect score and attitude score were significantly positively correlated with practice score (r=0.384, 0.309; P<0.001, 0.002). Further Pearson regression analysis revealed that the knowledge and attitude, education, Type 2 diabetes, were significantly associated with the practice of patients.

Conclusion

The CBDS recurrence patients had a good command of knowledge, but had negative attitude and poor performance in practice.
“The Metagenomics Days”: a simplified workshop on amplicon sequencing analysis with open cloud bioinformatics for eDNA and Microbiomes
Authors: Belaouni Hadj Ahmed , Stevenson Michael , Rosell Stewart , McClure Andrew
Published: December 2024

The “Metagenomics Days” event was organized to enhance understanding of metagenomics and microbiome analysis among participants new to the field. This paper presents an evaluation of the course’s impact through a comprehensive survey administered before and after the event. We assessed participants’ prior knowledge, experience with bioinformatics tools, and confidence levels regarding key concepts in microbiome analysis. Word clouds generated from open-ended survey responses provided additional insights into participants’ interests and pre-course familiarity with metagenomic tools and concepts. Surveys results showed substantial improvements in participants’ confidence, particularly in building bioinformatics pipelines (+41%), understanding diversity metrics (+44.1%), and applying microbiome analysis concepts (+34.8%). Similarly, understanding of core topics like cloud computing (+28%), bioinformatics workflows (+34%), and 16S rRNA gene variable regions (+27.5%) increased significantly. The course’s impact on knowledge retention was also evaluated, with participants achieving an average of 64.87% correct responses, with 25.76% unsure answers and only 9.35% incorrect responses, highlighting the effectiveness of the course in enhancing comprehension. Overall, the survey results indicate a significant increase in participants’ confidence and knowledge acquisition, particularly in the areas of cloud computing, diversity metrics, and bioinformatics pipelines. These improvements in confidence and knowledge acquisition underscore the effectiveness of the course in bridging knowledge gaps and preparing participants for future research in the complex and rapidly evolving fields of metagenomics and microbiome analysis.
Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays
Authors: Chen Yijun , Albert Ally L. , Sehrawat Anuradha , Farinas Marissa , Lopez Oscar L. , Zeng Xuemei , Cohen Ann D. , Karikari Thomas K.
Published: December 2024

Background

Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer’s disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum p-tau217 largely unexplored despite serum being a preferred matrix in many clinical laboratories. To address this gap, we compared p-tau217 concentrations and diagnostic performances in matched plasma and serum samples using four research-use-only assays, including three from commercial sources i.e., Lumipulse, ALZpath, NULISA, and one from University of Pittsburgh.

Methods

Paired plasma and serum samples were processed from the same venipuncture collection and assessed with the four p-tau217 assays following manufacturer-recommended procedures in two research cohorts (N=84).

Results

Plasma and serum p-tau217 levels varied across assays; the ALZpath, Pittsburgh, and NULISA methods showed significantly lower p-tau217 levels in serum compared with plasma (p<0.0001), while Lumipulse showed higher or non-significant differences in serum. Yet, strong correlations (rho >0.8) were observed between plasma and serum p-tau217 pairs. Both plasma and serum p-tau217 demonstrated strong classification accuracies to differentiate clinical AD from normal controls, with high AUC (up to 0.963) for all methods. The exception was the Pittsburgh assay, where plasma p-tau217 had superior AUC than serum p-tau217 (plasma: 0.912, serum: 0.844). The rest of the assays had equivalent accuracies in both matrices.

Conclusions

Serum p-tau217 performs equivalently as plasma p-tau217 for most assessed assays. Serum can therefore be used in place of plasma for p-tau217 assessment for research and clinical purposes.
PHALCON: phylogeny-aware variant calling from large-scale single-cell panel sequencing datasets
Authors: Priya  , Chowdary Sunkara B V , Zafar Hamim
Published: December 2024

Single-cell sequencing (SCS) technologies provide cellular resolution data for inferring variants and reconstructing tumor phylogeny for resolving intra-tumor heterogeneity (ITH), which causes drug resistance and relapse in cancer. Moreover, recently emerged panel sequencing methods can parallely sequence thousands of cells by targeting disease-specific genes. Current variant callers and SCS-specific phylogenetic methods fail to handle such large-scale datasets or address the amplification biases in panel-based sequencing protocols. Here, we present a statistical variant caller, PHAL-CON, which enables scalable mutation detection from large-scale single-cell panel sequencing data by modeling their evolutionary history under a finite-sites model along a clonal phylogeny. PHAL-CON infers the underlying cellular sub-populations based on mutation likelihoods of candidate sites and reconstructs a clonal phylogeny and the most likely mutation history using a likelihood-based probabilistic framework. Using numerous simulated datasets across varied experimental settings, we showed that PHALCON outperforms state-of-the-art methods in terms of variant call-ing accuracy (7.29-51.67% improvement), accuracy of tumor phylogeny inference (410.43-32931.8% improvement) and runtime (40-50×faster). Furthermore, when applied on datasets from triple negative breast cancer patients, PHALCON detected novel somatic mutations with high functional impact in important oncogenes and tumor suppressor genes, and better resolved ITH by identifying rare clones, and elucidating lineages harboring deleterious mutations in key oncogenes and tumor suppressor genes.
A new nanoDSF approach to anti-tubulin compounds screening revealed novel MTAs among approved drugs
Authors: Baksheeva Viktoriia E , La Rocca Romain , Leloup Ludovic , Souberan Aurelie , Bergès Raphael , Allegro Diane , Derviaux Carine , Pasquier Eddy , Roche Philippe , Morelli Xavier , Devred François , Tchoghandjian Aurélie , Tabouret Emeline , Golovin Andrey V , Tsvetkov Philipp O
Published: December 2024

Microtubule Targeting Agents (MTAs) constitute a vital category of tubulin-binding compounds, deployed across anticancer therapies. Despite the array of MTA drugs developed by pharmaceutical entities, the quest for novel efficacious molecules continues unabated. We unveil an innovativein vitroMTA screening methodology employing nano differential scanning fluorimetry (nanoDSF), presenting distinct advantages over known assays. This novel approach not only assesses compound-tubulin binding but also quantitatively analyzes their impact on tubulin polymerization. Proposed nanoDSF assay was rigorously validated using the Prestwick Chemical Library, which encompasses 1,520 approved compounds, successfully identifying all previously known MTAs. Furthermore, this screening has unearthed potential anti-tubulin agents among drugs currently utilized for non-related medical conditions, offering insights into their mechanisms of action in inhibiting cancer cell proliferation and/or inducing cytotoxicity. These discoveries herald new opportunities for drug repositioning involving the newly identified MTAs and substantially streamline the process of screening extensive chemical libraries for MTAs featuring novel chemical structures.
Tertiary and quaternary structure remodeling by occupancy of the substrate binding pocket in a large glutamate dehydrogenase
Authors: Lázaro Melisa , Chamorro Nicolás , López-Alonso Jorge P. , Charro Diego , Rasia Rodolfo M. , Jiménez-Osés Gonzalo , Valle Mikel , Lisa María-Natalia
Published: December 2024

Glutamate dehydrogenases (GDHs) catalyze the oxidative deamination of L-glutamate to 2-oxoglutarate using NAD(P)+as a cofactor. The large type of GDHs (L-GDHs) displays a dynamic homotetrameric architecture that alternates between open and closed states. The catalytic mechanism and the role of the large conformational changes of L-GDHs in enzymatic function are unknown. Here, we explore by cryoEM the structure and the conformational space of the mycobacterial L-GDH composed of 180 kDa subunits (mL-GDH180) when incubated with L-glutamate and NAD+. Classification of the heterogeneous population of tetramers into different subsets reveals opening-closing motions and sorting of individual subunits resolves the occupancy of the cofactor and substrate binding pockets. Maps show that ligand binding to the glutamate binding pocket is accompanied by structural changes in a distant region that mediates a novel interaction between the catalytic domains of neighboring subunits in closed tetrameric states. Our findings indicate that the occupancy of the orthosteric site of mL-GDH180is linked to a remodeling of the enzyme tertiary and quaternary structure.
The GPR4 antagonist NE-52-QQ57 increases survival, mitigates the hyperinflammatory response and reduces viral load in SARS-CoV-2-infected K18-hACE2 transgenic mice
Authors: Wu Xin-Jun , Oppelt Karen A. , Fan Ming , Marie Mona A. , Swyers Madison M. , Williams Ashley J. , Lemasson Isabelle M. , Roper Rachel L. , Bolin Paul , Yang Li V.
Published: December 2024

COVID-19 (Coronavirus disease 19) is caused by infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the respiratory system and other organ systems. Tissue injuries resulting from viral infection and host hyperinflammatory responses may lead to moderate to severe pneumonia, systemic complications, and even death. While anti-inflammatory agents have been used to treat patients with severe COVID-19, their therapeutic effects are limited. GPR4 (G protein-coupled receptor 4) is a pro-inflammatory receptor expressed on vascular endothelial cells, regulating leukocyte infiltration and inflammatory responses. In this study, we evaluated the effects of a GPR4 antagonist, NE-52-QQ57, in the SARS-CoV-2-infected K18-hACE2 transgenic mouse model. Our results demonstrated that GPR4 antagonist treatment increased the survival rate in this severe COVID-19 mouse model. The inflammatory response, characterized by proinflammatory cytokines and chemokines, was reduced in the GPR4 antagonist group compared with the vehicle group. Additionally, both SARS-CoV-2 RNA copy numbers and infectious viral titers in the mouse lung were decreased in the GPR4 antagonist group. The percentage of SARS-CoV-2 antigen-positive mouse brains was also decreased in the GPR4 antagonist group compared to the vehicle group. Furthermore, the GPR4 antagonist inhibited SARS-CoV-2 propagation in Vero E6 cells. Together, these results suggest that GPR4 antagonism may be explored as a novel approach for the treatment of COVID-19 and other similar viral diseases.