bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual selection matters in genetic rescue, but productivity benefits fade over time: a multi-generation experiment to inform conservation
Authors: West George , Pointer Michael , Nash Will , Lewis Rebecca , Gage Matt J. G. , Richardson David S.
Published: January 2025

Globally, many species are threatened by population decline because of anthropogenic changes leading to population fragmentation, genetic isolation and inbreeding depression. Genetic rescue, the controlled introduction of genetic variation, is a method used to relieve such effects in small populations. However, without understanding how the characteristics of rescuers impact rescue attempts interventions run the risk of being sub-optimal, or even counterproductive. We use the red flour beetle (
Tribolium castaneum
) to test the impact of rescuer sex, and sexual selection background, on population productivity. We record the impact of genetic rescue on population productivity in 24 and 36 replicated populations for ten generations following intervention. We find little or no impact of rescuer sex on the efficacy of rescue but show that a background of elevated sexual selection makes individuals more effective rescuers. In both experiments, rescue effects diminish 6–10 generations after the rescue. Our results confirm that the efficacy of genetic rescue can be influenced by characteristics of the rescuers and that the level of sexual selection in the rescuing population is an important factor. We show that any increase in fitness associated with rescue may last for a limited number of generations, suggesting implications for conservation policy and practice.
Penetrance of Parkinson’s disease inGBA1carriers is depending on the variant severity and polygenic background
Authors: Hassanin Emadeldin , Landoulsi Zied , Pachchek Sinthuja ,   NCER-PD Consortium, Krawitz Peter , Maj Carlo , Krüger Rejko , May Patrick , Bobbili Dheeraj Reddy
Published: January 2025

Background

Heterozygous variants in theGBA1gene cause Parkinson’s disease (PD) with variable penetrance and have been classified into severe, mild, and PD-specific risk variants based on their association with Gaucher’s disease (GD; mild and severe) or PD (risk variants). Polygenic risk scores (PRS) further modify PD susceptibility and may influence the age of onset inGBA1variant carriers. Our study investigates the interaction between a genome wide PRS and pathogenicGBA1variants (GBA1PVs), focusing on how established combined PD risk polymorphisms may influenceGBA1-related PD risk across different levels ofGBA1-mediated pathogenicity.

Methods

GBA1variants were identified from whole exome sequencing data in the UK Biobank (UKB) cohort and fromGBA1-targeted PacBio sequencing in the Luxembourg Parkinson’s Study (LuxPark). PRSs were calculated for all participants using established genome-wide significant SNPs, excluding variants within theGBA1locus, and then categorized based on both PRS levels andGBA1PVscarrier status. Carriers ofGBA1PVswere further divided into ‘severe (Gaucher-related) +mild (PD-related)’ and ‘risk’ groups. To evaluate the relationship between PRS,GBA1PVscarrier status or severity, and PD risk, logistic regression and Cox proportional hazards regression were conducted with disease presence as the dependent variable.

Results

We identifiedGBA1PVsin 8.8% of PD patients in the UKB discovery cohort and 9.9% in the LuxPark replication cohort.GBA1PVscarriers had consistently higher PD risk compared to non-carriers across all PRS categories. In UKB,GBA1PVscarriers in the highest PRS category had a 2.3-fold increased risk of PD (OR: 2.34; 95% CI, 2.08-2.63) and cumulative incidence of 67% by the age of 75, while those in LuxPark had a 1.6-fold higher risk (OR: 1.64; 95% CI, 1.52-1.76), and cumulative incidence of 81% at the age of 75. Carriers of “severe+mild”GBA1variants had nearly double the risk of PD compared to “risk” variant carriers, with ORs ranging from 2.05 to 3.69 in UKB and 1.73 to 1.98 in LuxPark. The interaction between the PRSs andGBA1PVsseverity was similar in the two cohorts.

Conclusions

Our findings demonstrate thatGBA1PVscarrier status and severity significantly impact PD risk, with severe variants conferring higher risk than risk ones. Additionally, PRS consistently increases both PD risk andGBA1PVspenetrance in an additive manner across all variant types, defining a genetic background that influences PD penetrance inGBA1PVscarriers. The presence of additional PD-associated risk variants inGBA1carriers defines new avenues to incorporate PRS and genetic risk data into future clinical trial design and genetic counselling inGBA1-associated PD.
Sex-specific metabolic signatures of adiposity associated with clinical biomarkers in the UK Biobank
Authors: Papagiannopoulos Christos K. , Markozannes Georgios , Chalitsios Christos V. , Christakoudi Sofia , Gunter Marc J , Dossus Laure , Martin Richard M. , Tzoulaki Ioanna , Papandreou Christopher , Tsilidis Konstantinos K.
Published: January 2025

Excessive adiposity increases disease risk, yet the exact underlying mechanisms remain unknown. We compared sex-specific metabolic signatures (MSs) of adiposity indices (non-allometric: body fat %, waist circumference, hip circumference, waist-to-hip ratio, body mass index; allometric: a body shape index, hip index, waist-to-hip-index ratio) and examined their associations with 29 clinical biomarkers in 151,526 UK Biobank participants. MSs performance was validated in an independent cohort. In females, MSs mainly consisted of lipoprotein particle concentrations, apolipoproteins, fatty acids and inflammation-linked glycoprotein acetyls, whereas in males lipoproteins rich in cholesteryl esters and aromatic/branched-chain amino acids predominated. The highest percentages of common metabolites were observed between non-allometric adiposity indices (median: 42.4%; range: 9%–56%). MSs were independently associated with over 25 biomarkers with differences observed by sex and adiposity index, and these associations were stronger compared to the respective phenotypic associations. MSABSI was found to be more atherogenic, whereas MSHI was more favourable for health. This study highlights i) that different regions of adipose tissue undergo distinct metabolic processes overall and by sex, each having unique impact on health, and ii) the importance of considering metabolic factors beyond simple adiposity indices in assessing health risk.
Explainable advanced electrocardiography at rest can rule out myocardial ischemia on stress echocardiography
Authors: Yang Kevin X , von Scheele Johan , Maanja Maren , Loewenstein Daniel E , Schlegel Todd T , Ugander Martin , Kozor Rebecca
Published: January 2025

Background: Stress echocardiography (SE) is relatively resource intensive and has a low incidence of abnormal tests for detecting coronary artery disease (CAD) in low-to-intermediate risk patients. This study aimed to derive and determine the diagnostic performance of a resting advanced electrocardiography (A-ECG) score for detecting inducible myocardial ischemia on SE in patients with low-to-intermediate risk stable chest pain. Methods: Patients were included if they presented with low-to-intermediate risk stable chest pain to the emergency department, had acute coronary syndrome ruled out by electrocardiography (ECG) and high-sensitivity troponin, and subsequently underwent outpatient SE. Patients were excluded if they had known CAD or confounders on resting ECG. A-ECG was retrospectively applied to a standard resting 12-lead ECG and a multivariable logistic regression score was derived to predict myocardial ischemia on SE. Results: Among 292 patients (51% male, age 58+/-14 years), 24 (8%) exhibited inducible myocardial ischemia on SE. A 3-parameter A-ECG score had an area under the receiver-operating characteristic curve (AUC [bootstrapped 95% confidence interval]) of 0.85 [0.75-0.93], sensitivity 92 [67-100]%, specificity 67 [64-94]%, positive predictive value 22 [20-55]%, negative predictive value 99 [96-100]%, positive likelihood ratio 2.8 [2.5-12.0] and inverse negative likelihood ratio 8.1 [2.5-18.0]. Conclusions: An A-ECG score had a good overall diagnostic performance and excellent performance for ruling out inducible myocardial ischemia on SE. This supports the use of an A-ECG score to triage and improve the selection of patients with low-intermediate risk stable chest pain that should undergo further testing with SE.
Global trends and prevalence of scabies: a spatiotemporal analysis using Global Burden of Disease 2021 data
Authors: Gupta Saptorshi , Thornley Simon , Morris Arthur , Sundborn Gerhard , Grant Cameron
Published: January 2025

Background

Scabies is a neglected disease believed to be more prevalent in resource-poor nations. Data describing global temporal trends of scabies incidence and prevalence and risk factors is limited.

Methods

This paper uses joinpoint regression and spatial analysis to estimate age-standardized rates (ASR) of scabies incidence and prevalence and temporal trends in 204 countries and regions from 1990 to 2021. Local indicators of spatial association were used to determine contiguous areas of high prevalence. The association of socio-demographic and economic factors with scabies was determined using locally weighted scatterplot smoothing and log-normal regression models.

Findings

Global prevalence of scabies in 2021 was 2.71% (95% confidence interval [CI]: 2.41 to 3.04%). Age-standardized rates of scabies have marginally declined globally from 1990 to 2021 with an Average Annual Percentage Change (AAPC) of -0.10 (95% CI -0.05 to -0.14) for incidence and -0.09 (95% CI -0.05 to -0.14) for prevalence. Spatial clustering of high scabies prevalence was present in tropical Latin America, Southeast Asia, and the Pacific Islands. Rates have shown an increasing trend in high-income regions such as Australasia and parts of Europe. Scabies showed a declining trend from middle to high socio-demographic index (SDI) regions. There is a significant positive association between warmer latitudes and increasing urbanization and scabies prevalence.

Interpretation

Scabies prevalence remains high in many regions. Control programmes should be prioritized to accelerate progress to reduce prevalence of this important neglected disease.
Pediatric Spigelian Hernia and Spigelian-Cryptorchidism Syndrome: an Integrating Review
Authors: Arredondo Montero Javier , Rico-Jiménez María
Published: January 2025

Introduction

Spigelian hernia (SH) is an aponeurotic defect, either acquired or congenital, in Spiegel’s semilunar line. SH is exceptional in pediatric patients.

Methods

A comprehensive non-systematic review of the previous literature was conducted. Eligible studies were identified by searching the primary existing medical bibliography databases. Median and interquartile range or mean and standard deviation were used to describe quantitative variables and proportions for categorical variables. The Kruskal-Wallis, Mann-Whitney U, and Fisher’s exact tests were used to compare group variables. The Spearman, Pearson and Cramér’s V correlation analyses were used to assess the degree of correlation between the study variables. A p-value <0.05 (two tails) was considered statistically significant.

Results

Eighty-two publications reporting 123 patients were included. Of these, 105 were male (85.4%). The age range was from 0 to 21 years. Forty-seven patients (38.2%) had a left-sided SH, and 13 (10.6%) had a bilateral SH. Forty-five cases (36.6%) were classified as traumatic, the majority attributable to bicycle-related injuries. Forty-one patients (33.3%) presented with a SH associated with undescended testis (UDT). A peak incidence around 7-9 years was identified for traumatic SH, and a concentration of cases before one year of age for SH associated with UDT. Fifteen patients (12.2%) were reported to have hernia incarceration/strangulation (I/S). These patients were significantly younger than those without I/S (p=0.02), but no gender differences were seen (p=0.63). In 95 patients (77.2%), surgical correction of the defect was reported. Fourteen were approached laparoscopically, with a 35.7% conversion rate. Eight (6.5%) were managed conservatively. Overall, the reported evolution has been favorable.

Conclusions

HS is an uncommon condition in pediatric populations, predominantly affecting males. It can present congenitally, with a significant association with ipsilateral UDT, or it can be acquired, typically related to bicycle trauma involving the SL. The risk of incarceration is relatively high, particularly during early childhood. Most reported cases have been treated surgically, with favorable outcomes. Evidence regarding conservative management is limited.
Aflatoxin M1 exposure and nutritional status of breastfeeding children 0-6 months in Makueni County, Kenya
Authors: Ogallo Isaac O. , Kaindi Dasel W. M. , Abong’ George O. , Mwangi Alice M.
Published: January 2025

Aflatoxin exposure in breastfeeding children has yet to be extensively explored in the southeastern region of Kenya, which is prone to aflatoxin outbreaks, and the assessment of potential risks may be underestimated. We determined the aflatoxin exposure of children 0-6 months and the outcome of weight-for-age z-scores as part of a larger cross-sectional study involving 170 randomly selected mother-child dyads. A semi-structured questionnaire was used to collect information on breastfeeding practices. Children’s weights were also measured. Breast milk samples of 48 lactating mothers and their children’s urine were collected from households whose food samples were collected for aflatoxin analysis. Aflatoxin levels were determined using enzyme-linked immunosorbent assays. The Statistical Package Software for Social Sciences (version 27) and Palisade’s @Risk software were used for analysis.

Exclusively breastfeeding children were 44.1% (75/170). The prevalence of aflatoxin M1 in breast milk was 77.1% (37/48) (concentration 35 ng/l;SD, 0.0), and the mean intake was 0.47 mg/kg b.w.t/day. All urine (100%) had aflatoxin M1 (mean 0.39 ng/ml (SD, 0.16). The exposure levels through breast milk were alarmingly high (margin of exposure < 10000) regardless of breastfeeding status, with complementary feeding potentially increasing the risks. Mothers’ diets significantly contributed to aflatoxin M1 in breast milk and urine (p= 0.01). Socioeconomic status, household size, and age of lactating mothers were not significant predictors of aflatoxin M1 exposure (p> 0.05). Aflatoxin M1 exposure did not influence the weight-for-age z-scores (pall> 0.05). The results indicate high exposure levels among children 0-6 months, and breastfeeding practices could be one of the under-evaluated risk factors.
Development of a Claims-Based Computable Phenotype for Ulcerative Colitis Flares
Authors: Copeland Daniel , Marwaha Jayson S. , Wong Daniel , Yuan William , Fakler Michelle N. , Kennedy Chris J. , Beaulieu-Jones Brendin , Poylin Vitaliy , Feuerstein Joseph , Brat Gabriel A.
Published: January 2025

Background and Aims

Several conditions exist that do not have their own unique diagnosis code in widely-used clinical terminologies, making them difficult to track and study. Acute severe ulcerative colitis (ASUC) is one such condition. There is no automated method to identify patients admitted for ASUC from observational data, nor any specific billing or diagnosis code for ASUC. Accurate, automated, large-scale identification of hospital admissions for non-coded conditions like ASUC may enable further research into them.

Methods

We performed a retrospective cohort study of patients with a history of ulcerative colitis (UC) admitted to a single academic institution from 2014-2019. Clinicians at our institution performed a chart review of these admissions to determine if each was due to a true episode of ASUC or not. Logistic regression, random forest (RF), and support vector machine (SVM) models were trained upon administrative claims data for all admissions.

Results

268 ASUC admissions and 3,725 non-ASUC admissions among UC patients were included. Our RF model exhibited the best performance, correctly classifying 95.5% of admissions as either ASUC or non-ASUC, with a validation AUROC of 0.96 (95% CI 0.94-0.98; AUPRC 0.73). The model had a sensitivity of 81.5% and specificity of 96.5%. The five most important features in the model were endoscopy of sigmoid colon, length of stay, age, endoscopy of rectum, and abdominal x-ray.

Conclusions

There is currently no modality by which ASUC, which does not have its own unique diagnosis code, can be identified from claims databases in a scalable fashion for research or clinical purposes. We have developed a machine learning-based model that identifies clinically significant ASUC and reliably distinguishes them from admissions for non-ASUC reasons among UC patients. The ability to automatically curate large, accurate datasets of non-coded conditions like ASUC episodes can serve as the basis of large-scale analyses to maximize our ability to learn from real-world data, enable future research, and better understand these diseases.

There is currently no accurate way to identify, track, or study acute severe ulcerative colitis (ASUC) using administrative claims datasets. We have built a machine learning model to identify ASUC from claims data to enable large-scale studies on this condition.
Knowledge, Attitude and Practices (KAP) of Antimicrobial Usage in in Kisii County, Kenya
Authors: Babafemi Emmanuel O , Omasaki Simion K , Mogoko Edward , McCabe Philippa G
Published: January 2025

Background

Antimicrobial stewardship (AMS) policy is critical in tackling antimicrobial resistance (AMR). The information is available at the national level in Kenya about AMS policy but needed to be strengthened among the health workers and facilities at the county level. The aim of this study was to conduct a baseline assessment of the Knowledge, Attitude and Practices (KAP) on Antimicrobial Prescription and its Resistance Among Health Care Providers in Resource Poor Settings using Kisii County, Kenya as case study.

Methods

A paper-based survey was conducted among Public, Private Health facilities and Community Pharmacies in Kisii County between October and December 2023. The data collected from the respondents were put into Microsoft Excel spreadsheet for coding before being imported to RStudio for analysis.

Results

A total of 154 facilities across the 45 wards in Kisii County were included in the study. Most participants 111 (72%) agreed they have not received training and education on AMR and its implications on public health. Similarly,75 (49%) of the respondents said they have no formal procedures for all prescribers to conduct daily reviews of antibiotic selection until a definitive diagnosis and treatment duration are established. And that, they were not aware of AMS policy. However, they would be interested in workshops to educate them on AMR/AMS. Finally, on the level of awareness of the diagnosis and surveillance of AMR mechanisms, 248 (40%) responses said they were not or not very familiar with Methicillin-resistantStaphylococcus aureus(MRSA), Vancomycin-resistant Enterococci (VRE), Extended-Spectrum Beta-Lactamases (ESBLs), Carbapenemase-producing enterobacterales (CPE), Multidrug-resistant tuberculosis (MDR-TB) etc.

Conclusion

This study found limited level of AMS implementation/uptake across all the facilities studied in Kisii County, Kenya. The study identified challenges that require urgent action in strengthening AMS policy. AMS training and education would be more effective if they are designed to specific healthcare specialties and communities/facilities in Kisii County.
Prevalence of Hyperglycemia in Pregnancy using early, standard and late screening: a study in the Primary Care Health in Lima, Peru
Authors: Seclén S.N. , Damas-Casani Lucy Nelly , Motta-Montoya Vicky Delia Cecilia , Jiménez-Martel Sandra Lesly , Yovera-Aldana Marlon
Published: January 2025

Objective

To determine the prevalence of hyperglycemia in pregnancy (HIP) based on the timing of screening in pregnant women.

Materials and Methods

A cross-sectional study was conducted on pregnant women recruited from February 2019 to August 2022 in four primary care centers in Lima, excluding those with known diabetes. Screening involved an Oral Glucose Tolerance Test with 75 g of glucose at the first contact. It was classified as early if performed before 24 weeks, standard between 24-28 weeks, and late if after 29 weeks. For gestational diabetes mellitus (GDM), we used the IADPSG diagnostic criteria for any gestational age. For diabetes in pregnancy (DIP), glucose levels over 126 mg/dl fasting or over 200 mg/dl at 2 hours post-load were used. We calculated prevalence ratios for GDM and DIP based on the type of screening.

Results

We included 4,495 pregnant women with an average age of 29 years. The prevalence of HIP was 14.9%, GDM was 14.2%, and DIP was 0.7%. Early GDM screening showed a 23% higher prevalence compared to GDM screening at 24-28 weeks, adjusted for age (PR 1.23; 95% CI 1.01 – 1.49; p=0.036). No differences were found for DIP across screening types.

Conclusion

In pregnant women at four primary centers in Lima, one in seven pregnant women (14.9%) had HIP, GDM was 14.2%, and DIP was 0.7%.. Early screening showed the highest proportion of GDM compared to standard or late screening. Longitudinal studies are needed to validate whether this higher early prevalence impacts maternal-perinatal complications.
A Randomized Controlled Trial Evaluating the Effect of Adalimumab Upon Pre-Clinical Biomarkers of Cardiovascular Disease in ACPA-Positive Rheumatoid Arthritis
Authors: Oakley Stephen P , Gibberd Alison J , Oldmeadow Christopher , Thomas Ranjeny , Nel Hanno , Esmaili Niloofar , Weston Lyanne
Published: January 2025

Objectives

Rheumatoid arthritis (RA) is associated with elevated risk of cardiovascular (CV) events that has been attributed to inflammation although this is not well supported by randomised controlled trial (RCT) data. This RCT evaluated the effect of adalimumab upon endothelial function and arterial stiffness in ACPA-positive RA.

Methods

Sixty subjects with active ACPA-positive RA stratified as Early (<12 months n=30) or Established (>12 months n=30) were enrolled and randomised 1:1 within each group to receive 40 mg adalimumab or placebo. They were assessed by DAS28-CRP, Reactive Hyperaemic Index (RHI) and Carotid-Femoral Pulse Wave Velocity (CF-PWV) twice prior to treatment and then at 1, 4, 12 and 24 weeks with one final open-label at 36 weeks. Secondary analysis evaluated the effects of disease duration, Shared Epitope (SE) and smoking status.

Results

There were significant treatment effects upon DAS28-CRP at weeks 1, 4 and 12 in Early RA with transient effects upon RHI at week 1 in Established RA and CF-PWV in Early RA at week 4. Area-under-the-curve analysis found positive treatment effects in subjects expressing one SE (DAS28-CRP p 0.031, CF-PWV p 0.034) and in non-smokers (DAS28-CRP p 0.096, CF-PWV p 0.033).

Conclusions

This RCT appeared to show positive treatment effects upon CV risk. However, the effect of adalimumab upon RHI may be type 1 statistical error and the effect upon CF-PWV more likely represents physiologic pain-driven mechanisms rather than structural effects. This study highlights the challenges, the limitations, strengths of and opportunities for CV biomarker research in this complex field.
Predicting Dementia in People with Parkinson's Disease
Authors: Aborageh Mohamed , Hähnel Tom , Martins Conde Patricia , Klucken Jochen , Fröhlich Holger
Published: January 2025

Parkinson's disease (PD) exhibits a variety of symptoms, with approximately 25% of patients experiencing mild cognitive impairment and 45% developing dementia within ten years of diagnosis. Predicting this progression and identifying its causes remains challenging. Our study utilizes machine learning and multimodal data from the UK Biobank to explore the predictability of Parkinson's dementia (PDD) post-diagnosis, further validated by data from the Parkinson's Progression Markers Initiative (PPMI) cohort. Using Shapley Additive Explanation (SHAP) and Bayesian Network structure learning, we analyzed interactions among genetic predisposition, comorbidities, lifestyle, and environmental factors. We concluded that genetic predisposition is the dominant factor, with significant influence from comorbidities. Additionally, we employed Mendelian randomization (MR) to establish potential causal links between hypertension, type 2 diabetes, and PDD, suggesting that managing blood pressure and glucose levels in Parkinson's patients may serve as a preventive strategy. This study identifies risk factors for PDD and proposes avenues for prevention.
Epigenetic attenuation of interferon signaling drives aging-related improvements in systemic lupus
Authors: Narendra Rithwik , Phan Hoang Van , Patterson Sarah L. , Almonte Loya Ana Laura , Lanata Cristina , Love Christina , Park Joonsuk , Lydon Emily C. , Shimoda Michiko Ametani , Barcellos Lisa , Mekonen Honey , Detweiler Angela , Deosthale Padmini , Neff Norma , Criswell Lindsey A. , Maliskova Lenka , Eckalbar Walter , Fragiadakis Gabriella , Yazdany Jinoos , Dall’Era Maria , Katz Patricia , Ye Chun Jimmie , Sirota Marina , Langelier Charles R.
Published: January 2025

In the general human population, aging is associated with a rise in systemic inflammation, primarily involving innate immune pathways related to interferon (IFN), toll-like receptor, and cytokine signaling. In systemic lupus erythematosus (SLE), a prototypical systemic autoimmune disease, aging is distinctly associated with improvements in disease activity, suggesting a unique relationship between aging and inflammation in this disease. Using a multi-omic approach incorporating transcriptional profiling, single cell RNA sequencing, proteomics and methylation analysis, we studied age-related changes in the immune profiles of 287 SLE patients between 20 and 83 years old, and compared the results against 928 healthy controls aged between 21 and 89 years old. In contrast to the increase in inflammatory gene expression that occurs with aging in most healthy adults, SLE patients exhibited the opposite. Most notable was a decrease in type I IFN signaling that was evident across multiple cell types, with CD56-dim natural killer (NK) cells, CD4+effector memory T cells, and naïve B cells exhibiting the most significant differences. We found that aging in SLE patients was also associated with decreased IFN-α2 and IFN-λ1 levels, and differential methylation of the genome. Notably, of the genes both downregulated and hypermethylated with older age, IFN-related genes were disproportionately represented, suggesting that age-related decreases in IFN signaling were driven in part by epigenetic silencing. Both SLE patients and healthy controls demonstrated age-related declines in naïve T cells and lymphoid progenitor cells, but only SLE patients demonstrated age-related increases in CD56-dim NK cells. Taken together, our work provides new insight into the phenomenon of inflammaging and the unique clinical improvement in disease activity that occurs in SLE patients as they age.
Knowledge and Awareness of Bovine Tuberculosis Associated with Raw Milk and Under-Cooked Meat Contamination Among Cattle Farmers in Selected Parts of Zambia
Authors: Phiri Anthony , Likulunga Emmanuel , Chauwa Adriace , Zulu Mildred , Kankhuni Beatrice , Monde Ngula , Malama Sydney
Published: January 2025

Background

Bovine tuberculosis (bTB) is a disease of cattle that is transmitted through direct contact with an infected animal or ingestion of contaminated food.

Methods

A mixed methods study was conducted in two districts of Zambia Lundazi and Monze from December 2021 to June 2022. A cross-sectional survey was conducted with 280 respondents, five focus group discussions, and five key informant interviews. Descriptive statistics were used to analyze quantitative data using R software while qualitative data was analyzed using Nvivo® and content analysis.

Results

Social and cultural practices were reported to significantly contribute to bTB transmission with risky behaviors including the consumption of undercooked meat and unpasteurised milk, and inadequate protective measures during cattle slaughtering. Overall, 75.3% of male and 70.3% of female respondents expressed a poor level of awareness of bTB transmission. Among cattle farmers, 85.7% lacked formal education, resulting in low knowledge levels, with 99.5% expressing poor awareness. Additionally, findings revealed that 99.5% of cattle farmers had poor awareness of bTB, human doctors/clinicians, and veterinary/para-veterinarians had 100% excellent knowledge. Abattoir workers had good knowledge at 78.3% and cattle businessmen had a fair knowledge level at 96.4%. Overall, bTB awareness varied across occupations, with human and animal healthcare professionals being the most knowledgeable.

Conclusions

Our study found low levels of awareness and misperception about bTB among cattle farmers. Awareness varied across professionals with educated individuals being more knowledgeable. The consumption of undercooked meat and raw milk highlighted these knowledge gaps. Therefore, it is crucial to conduct public health campaigns to raise awareness about bTB causes, sources of infection, and control measures.
Comparative Evaluation of Advanced AI Reasoning Models in Pediatric Clinical Decision Support: ChatGPT O1 vs. DeepSeek-R1
Authors: Mondillo Gianluca , Colosimo Simone , Perrotta Alessandra , Frattolillo Vittoria , Masino Mariapia
Published: January 2025

Introduction

The adoption of advanced reasoning models, such as ChatGPT O1 and DeepSeek-R1, represents a pivotal step forward in clinical decision support, particularly in pediatrics. ChatGPT O1 employs “chain-of-thought reasoning” (CoT) to enhance structured problem-solving, while DeepSeek-R1 introduces self-reflection capabilities through reinforcement learning. This study aimed to evaluate the diagnostic accuracy and clinical utility of these models in pediatric scenarios using the MedQA dataset.

Materials and Methods

A total of 500 multiple-choice pediatric questions from the MedQA dataset were presented to ChatGPT O1 and DeepSeek-R1. Each question included four or more options, with one correct answer. The models were evaluated under uniform conditions, with performance metrics including accuracy, Cohen’s Kappa, and chi-square tests applied to assess agreement and statistical significance. Responses were analyzed to determine the models effectiveness in addressing clinical questions.

Results

ChatGPT O1 achieved a diagnostic accuracy of 92.8%, significantly outperforming DeepSeek-R1, which scored 87.0% (p <0.00001). The CoT reasoning technique used by ChatGPT O1 allowed for more structured and reliable responses, reducing the risk of errors. Conversely, DeepSeek-R1, while slightly less accurate, demonstrated superior accessibility and adaptability due to its open-source nature and emerging self-reflection capabilities. Cohen’s Kappa (K=0.20) indicated low agreement between the models, reflecting their distinct reasoning strategies.

Conclusions

This study highlights the strengths of ChatGPT O1 in providing accurate and coherent clinical reasoning, making it highly suitable for critical pediatric scenarios.

DeepSeek-R1, with its flexibility and accessibility, remains a valuable tool in resource-limited settings. Combining these models in an ensemble system could leverage their complementary strengths, optimizing decision support in diverse clinical contexts. Further research is warranted to explore their integration into multidisciplinary care teams and their application in real-world clinical settings.
Impact of 3D Printed Models on Shared Decision Making: A Cluster Randomized Controlled Trial
Authors: Khan Aimal , Sellyn Georgina E. , Ali Danish , Moazzam Zorays , Samaras Hillary , McChesney Shannon , Hopkins M. Benjamin , Ford Molly M. , Muldoon Roberta , Geiger Timothy M. , Martin Dann , Chu Daniel L. , VanKoevering Kyle K. , Hawkins Alexander T.
Published: January 2025

Importance: Surgical patients report a lack of involvement in healthcare decisions and increased anxiety. 3D models serve as educational tools to encourage patient engagement, reduce anxiety levels, and aid understanding. We hypothesized that patients who receive pre-operative education with by 3D-printed anatomic models would perceive a higher involvement in decision making and experience lower anxiety levels versus "standard care." Objective: To determine the impact of 3D-printed models on shared decision making and patient anxiety during the pre-operative surgical consultation. Design: Single-center cluster randomized control trial. Setting: Colorectal surgery clinic at a tertiary hospital. Participants: Adult (18 years or older) patients scheduled for partial or complete colon and/or rectal resection. Intervention/s: Surgeons were cluster-randomized to counsel patients using a modular 3D-printed model or providing standard care during pre-operative clinic visits. Main outcomes: The primary outcome was the patient's perception of involvement in decision making, assessed using the validated Shared Decision Making Questionnaire (SDM-Q9). The secondary outcome was the change in anxiety level measured using the validated State-Trait Anxiety Inventory (STAI-6). Results: A total of 51 patients, 28 in the 3D-printed arm and 23 in the standard care arm, met the inclusion criteria and agreed to participate. The mean age of participants was 51.1 years, with 55% female. Patients counseled with the 3D-printed model reported significantly higher involvement in shared decision making (mean score of 93.9 [SD 8.8] vs. 82.9 [SD 12.1], p <0.001), which was also clinically significant. Additionally, using a 3D-printed model significantly reduced anxiety scores (47.3 [6.0] to 46.4 [5.6]) compared to patients taught using conventional methods (48.3 [7.4] to 51.1 [9.7], p <0.008), but this effect was not deemed clinically significant. Conclusions: The use of 3D models at pre-operative clinic visits improves shared decision making among patients planning to undergo colorectal surgery. Relevance: This study highlights the potential of using 3D-printed models as an effective tool for a more collaborative and informed patient-clinician interaction. Given the positive findings, we recommend broadly implementing this technology.
Personalized circulating tumor DNA dynamics predict survival and response to immune checkpoint blockade in recurrent/metastatic head and neck cancer
Authors: Ruiz-Torres Daniel A. , Merkin Ross D. , Bryan Michael , Mendel Julia , Efthymiou Vasileios , Roberts Thomas , Patel Manisha , Park Jong C. , Chevalier Amber , Murray Clodagh , Gates Lisa , Pipinikas Christodoulos , Stott Shannon L. , Fisch Adam S. , Wirth Lori J. , Faden Daniel L.
Published: January 2025

Background

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an aggressive cancer with a median overall survival of only 12 months. Existing biomarkers have limited ability to predict treatment response or survival, exposing many patients to the potential toxicity of treatment without certain clinical benefit. Circulating tumor DNA (ctDNA) has emerged as a non-invasive, real-time biomarker that could address these challenges.

Methods

We analyzed 137 plasma samples from 16 patients with R/M HNSCC undergoing immune checkpoint blockade (ICB)-based therapy. A tumor-informed, highly sensitive next-generation sequencing liquid biopsy assay (RaDaR, NeoGenomics Laboratories, Inc.) was applied to track ctDNA changes at baseline and throughout treatment. Univariable and multivariable analyses were used to assess the association between ctDNA negativity and key clinical outcomes: disease control (best objective response of stable disease, partial response, or complete response), three-year overall survival (OS), and three-year progression-free survival (PFS). We also assessed a machine learning model to predict disease progression based on ctDNA dynamics.

Results

Multivariable analysis revealed that ctDNA negativity during treatment was significantly associated with improved disease control (OR 21.7, 95% CI 1.86-754.88, p=0.0317), three-year OS (HR 0.04, 95% CI 0.00-0.47, p=0.0103), and three-year PFS (HR 0.03, 95% CI 0.00-0.37, p=0.0057). The machine learning model predicted disease progression with 88% accuracy (AUC 0.89).

Conclusion

Serial ctDNA monitoring predicted disease control, survival, and progression in patients with R/M HNSCC receiving treatment with ICB, suggesting that incorporation of ctDNA into clinical practice could enhance treatment decision-making for clinicians and improve patient outcomes.
Dementia risk factors and cognitive decline: Results from the 2023 Behavioral Risk Factor Surveillance System (BRFSS)
Authors: Adams Mary L.
Published: January 2025

Background

The potentially modifiable risk factors of obesity, diabetes, hypertension, smoking, physical inactivity, depression, hearing impairment, and excessive alcohol consumption, have been found to be associated with cognitive decline and dementia.

Objective

To study the association between subjective cognitive decline (SCD) among survey respondents and the 8 risk factors compared with other potential risks.

Methods

Using 2023 Behavioral Risk Factor Surveillance data from 155,112 respondents ages 45+ in 35 states with data on SCD the associations between the 8 dementia risk factors, separately and in a composite measure, plus other demographic and health measures were studied using Stata.

Results

SCD rates were 17.2% overall ranging from 11.0% to 23.9% across states while 81.9% of adults 45+ reported any of the 8 dementia risk factors. Adults with each of the risk factors had higher SCD rates compared with those without the risk factor, with SCD rates ranging from 8.4% for adults with 0 risks, 19.2% for any of the 8 risks, and 45.3% for those with 5 or more. Logistic regression confirmed most results with adjusted odds ratios (AORs) up to 6.0 for 5 or more risk factors, >3.1 for current long COVID and >1.2 for low education. Obesity was not confirmed as a separate risk and highest AOR for age was 1.2 for ages 75+ with 8 risk factors entered separately.

Conclusions

Results suggest that prevention efforts for SCD, which can be a step toward dementia, should focus on 8 common potentially modifiable risk factors plus long COVID.
Exposure to public housing reverses the association between neighborhood disadvantage and eosinophilic inflammation in patients with sickle cell disease
Authors: McCuskee Sarah , Chiu Yueh-Hsiu Mathilda , McCann Mariel , Wright Rosalind J , Glassberg Jeffrey A
Published: January 2025

Sickle cell disease (SCD) is a single-gene illness characterized by chronic inflammation, decreased quality of life, and early mortality; however, outcomes are highly variable between individuals, suggesting a substantial role of social and environmental factors in disease outcomes. Data suggest that individuals living with SCD have greater eosinophil counts and activation, and higher prevalence of asthma and wheezing than those without SCD, suggesting a role for eosinophilic inflammation in SCD. In other diseases, eosinophilic inflammation has been linked to social and environmental factors, particularly in minoritized populations. To date, however, few human studies have explored the pathophysiology of social and environmental exposures in SCD. This study tested whether eosinophilic inflammation was related to location-based measures of social disadvantage or public housing in 79 individuals with SCD, without diagnoses of asthma, who were prospectively followed over one year. Home addresses were geocoded and matched to principal-components derived, validated measures of local neighborhood social disadvantage and to locations of public housing facilities. Serum peripheral eosinophils, IL-13 and IL-5 were measured every 8 weeks. In fully-adjusted models, statistically significant, linear relationships were observed between the degree of social disadvantage and level of eosinophilic inflammation; however, the direction of that relationship was opposite for patients who live in public housing and those who do not. For those living in public housing, greater social disadvantage was associated with increased eosinophilic inflammation. For those in private housing, greater social disadvantage was associated with progressively less eosinophilic inflammation. These strong, and somewhat unexpected, relationships demonstrate that subtle differences in social exposures and home environment have differential effects on inflammatory profiles which may have larger implications for disease and health, especially in chronic diseases such as SCD. To understand the mechanisms of these effects may require highly granular studies that catalog the many factors underlying the social environment and inflammation.
Streamlining Large-Scale Genomic Data Management: Insights from the UK Biobank Whole-Genome Sequencing Data
Authors: Li Xihao , Wood Andrew R. , Yuan Yuxin , Zhang Manrui , Huang Yushu , Hawkes Gareth , Beaumont Robin N. , Weedon Michael N. , Li Wenyuan , Li Xiaoyu , Lin Xihong , Li Zilin
Published: January 2025

Biobank-scale Whole-Genome Sequencing (WGS) studies are increasingly pivotal in unraveling the genetic bases of diverse health outcomes. However, managing and analyzing these datasets’ sheer volume and complexity presents significant challenges. We proposevcf2agds, an all-in-one toolkit that efficiently converts WGS data from Variant Call Format (VCF) format to the annotated Genomic Data Structure (aGDS) format, significantly reducing data size while supporting seamless genomic and functional data integration for comprehensive genetic analyses. The toolkit was applied to the UK Biobank 500k WGS data, resulting in twenty-three aGDS files, one for each chromosome, which collectively compressed 1,473.85 Tebibytes of pVCF data into 1.10 Tebibytes. Utilizing these aGDS files, we conducted a functionally informed rare variant association analysis of total cholesterol employing theSTAARpipelineand detected 480 genome-wide significant coding and noncoding associations. Overall,vcf2agdsoffers a streamlined approach facilitating the efficient management and analysis of biobank-scale WGS data across hundreds of thousands of samples.
dnaSORA - A Unified Diffusion Transformer for DNA point clouds
Authors: Koreniuk Oleksandr , Njie eMalick G.
Published: January 2025

The relatively obscure Hawaiian experiment collapses diverse phenotypes, including nearly all human genetic diseases to a singular Gaussian-like point cloud feature, structuring unstructured information. The uniformity of the feature space provides a straightforward way for AI models to learn all three billion tokens for reading the human genome as a first language. We propose a diffusion transformer, dnaSORA, for learning these features. dnaSORA has generative capacity similar to Stable Diffusion but for DNA point clouds. The model’s architecture is novel because it is unified; thus, it also functions as a discriminator that uses a frozen latent representation for classification. dnaSORA transfer learns from synthetic data emulating real genome point clouds to classify misrepresented tokens inC. elegansHawaiian data at state-of-the-art 0.3 Mb resolution. Pre-training large genome models typically requires expensive and difficult-to-obtain genomes. However, our solution provides nearly unlimited synthetic training data at negligible compute costs. Inference for new token assignments (e.g., new diseases) requires genomes from several dozen rather than thousands of individuals. These efficiencies, combined with state-of-the-art resolution, provide a pathway for rapid, massive scaling of token annotation of the entire human genome at orders of magnitude below expected costs.
Structural basis for activation and potentiation in a human α5β3 GABAAreceptor
Authors: Cowgill John , Fan Chen , Stayaert Jan , Howard Rebecca J. , Lindahl Erik
Published: January 2025

General anesthetics like etomidate mediate amnesic as well as sedative effects through different populations of gamma amino butyric acid receptors (GABAARs) in the central nervous system. The amnesic effects have largely been attributed to α5-subunit-containing receptors in the hippocampus, indicating a clear role in learning and memory for these receptors. The α5 subunit is thought to primarily coassemble with β3 and, in some cases, γ2 subunits, generating a variety of receptor subtypes with differential functional and pharmacological properties. However, the stoichiometry, structure, and gating mechanisms of these different subpopulations are not well understood. Here we report structures of human α5β3 GABAARs with various modulators, assembled in two stoichiometries. Our cryo-EM structures, combined with electrophysiology inXenopusoocytes, support a primary assembly of 2:3 α:β subunits, though a minority population of 1:4 α:β indicates multiple assemblies are possible. Differential glycosylation of the α5 and β3 subunits enabled reconstruction of the heteromeric complex even in the absence of added fiducials. In the resting state of the receptor, Zn2+binds to histidine residues at the M2-17′ position in the β3 subunit, blocking ion passage. In the activated state, GABA binding to the orthosteric site is associated with global rearrangements propagating to unbinding of the 17′ Zn2+atoms and opening of the 9′ hydrophobic gate. Unlike the α1β3 receptor where GABA is effectively a partial agonist, saturating GABA binding to α5β3 appears to drive activation of nearly all receptors, resulting in a single desensitized state observed under the cryo-EM conditions. In agreement with this high GABA efficacy, the GABA-bound structure is virtually unaffected by further addition of the anesthetic etomidate at the β-α transmembrane domain interface. These structures offer new detailed models for gating and modulation of a GABAAR subtype critical to learning and memory, including prospective templates for structure-based drug discovery.