bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood glucose dynamics vary with economic provenance of meal
Authors: Hamill Daniel , Smith Trenton G. , Venn Bernard 
Published: November 2024

AbstractThe dynamics of blood sugar response to ultra-processed foods have strong parallels to the effects of addictive drugs. We hypothesize that if glycemic response is indeed an important determinant of habit formation–and hence product demand–then the largest producers of proprietary commercial foods will have formulated their products accordingly. We continuous glucose monitor (CGM) data from free-feeding adults spanning 579 meal events yielding a pooled time series dataset with more than 24,000 observations. We find strong evidence that addiction-like dynamic properties of the glycemic response (dose, rate of absorption, and withdrawal) are greater for globally branded fast food meals as compared to freshly-prepared or off-brand processed food meals. These differences are largely maintained when controlling for size of meal and nutrient content, suggesting that standard food labels may be insufficient to resolve what appears to be an important asymmetric information problem.
Bridging the Gap: Identifying Barriers and Strategies for Widespread Implementation of Long-acting Injectable Antiretroviral ART in Sub-Saharan Africa: A Scoping Review
Authors: Gashema Pierre , Iradukunda Patrick Gad , Saramba Eric , Musafiri Tumusime , Umuhoza Thérèse , Ndahimana Felix , Ingabire Angelique , Ndoli Moise Mukire , Mutagoma Gerard , Mwikarago Ivan Emil , Nyirimigabo Eric , Ribakare Muhayimpundu , de Dieu Harelimana Jean , Moyo Enos , Dzinamarira Tafadzwa , Muvunyi Claude Mambo 
Published: November 2024

ABSTRACTBackgroundLong-acting injectable antiretroviral therapy (LAI ART) presents a new approach to HIV treatment and addressing the challenges of daily oral ART in Sub-Saharan Africa (SSA) remains paramount. This review collates existing literature on barriers and strategies for implementing LAI ART in the SSA region, identifying knowledge gaps and research priorities.MethodsWe performed a thorough literature search, encompassing electronic databases and grey literature sources. Our review included 18 studies published between 2014 and 2023, focusing on the acceptability, feasibility, effectiveness, and cost-effectiveness of LAI ART in SSA. Data extraction involved study characteristics, population, intervention, outcomes, and context, with findings synthesized using a narrative approach.ResultsThe results indicate high demand and acceptability of LAI ART among people living with HIV in SSA, particularly those facing stigma and discrimination. LAI ART can improve adherence, retention, and viral suppression while reducing pill burden and frequent clinic visits. Implementation challenges include lack of regulatory approval, high cost, limited supply chain, health system capacity, trained staff, and cold storage facilities. Further evidence on safety and efficacy, advocacy, policy, and community engagement are needed to ensure accessibility and equity.ConclusionKnowledge gaps and research priorities include dosing regimens, long-term outcomes, drug resistance, impact on sexual and reproductive health, interactions with other medications and co-infections, and preferences and experiences of different subgroups.
Time-Series Deep Learning and Conformal Prediction for Improved Sepsis Diagnosis in Non-ICU Hospitalized Patients
Authors: Dalal Shaunak , Khaleghi Ardabili Ahad , Bonavia Anthony S. 
Published: November 2024

AbstractPurposeSepsis, a life-threatening condition from an uncontrolled immune response to infection, is a leading cause of in-hospital mortality. Early detection is crucial, yet traditional diagnostic methods, like SIRS and SOFA, often fail to identify sepsis in non-ICU settings where monitoring is less frequent. Recent machine learning (ML) models offer new possibilities but lack generalizability and suffer from high false alarm rates.MethodsWe developed a deep learning (DL) model tailored for non-ICU environments, using MIMIC-IV data with a conformal prediction framework to handle uncertainty. The model was trained on 83,813 patients and validated with the eICU-CRD dataset to test performance across hospital settings.ResultsOur model predicted sepsis at 24, 12, and 6 h before onset, achieving AUROCs of 0.96, 0.98, and 0.99, respectively. The conformal approach reduced false positives and improved specificity. External validation confirmed similar performance, with a 57% reduction in false alarms at the 6 h window, supporting practical use in low-monitoring environments.ConclusionsThis DL-based model enables accurate, early sepsis prediction with minimal data, addressing key clinical challenges and potentially improving resource allocation in hospital settings by reducing unnecessary ICU admissions and enhancing timely interventions.
PAIN RELIEF IN MAJOR AMPUTATION (PRIMA) PROTOCOL: A SINGLE CENTRE RCT COMPARING PRE-INCISION SINGLE-SHOT NERVE BLOCK AND PATIENT CONTROLLED ANALGESIA TO PRE-INCISION PERI-NEURAL CATHETER, IN PATIENTS UNDERGOING MAJOR LOWER LIMB AMPUTATION
Authors: Shelmerdine L. , Bentley R. , Baxter I , Nandhra S 
Published: November 2024

AbstractIntroduction9663 major lower limb amputations were performed in UK NHS hospitals, between 2018-2020. Despite this high number, there is no universally accepted peri-operative analgesia regime. The Vascular Society and Vascular Anaesthesia Society of Great Britain and Ireland, in partnership with patients (supported by the James-Lind Alliance), have identified improving outcomes (including preventing/treating pain) for patients who undergo amputations as a key research priority.Methods and methodsA prospective, single-blind, RCT (1:1), comparing pre-incision ultrasound sited PNC (7-day duration) or pre-incision ‘single-shot’ nerve block and PCA, for those undergoing MLLA. The sample size is 34 patients, powered to detect a primary outcome of 2.5cm(2cmSD) difference on a visual analogue scale (VAS) at day 3.Secondary outcomes include daily pain scores, analgesia use, post-operative nausea and vomiting, Pasero opioid-induced sedation scale and physiotherapy progress. Patient-reported neuropathic pain and quality of life tools (SF36 and EQ5D) are recorded at baseline, day-7, 6-weeks and one-year.Ethics and disseminationThis study was approved by South East Scotland Research Ethics Committee on 03/02/2021. REC reference:21/SS/0013). It is hoped this NIHR-portfolio adopted, RCS(Ed) funded RCT, will provide level-1 evidence for a shared patient and clinician research priority. Trial registration: ISRCTN.com,ISRCTN64207537. Registered on 21/07/2021
Epigenetic and Structural Brain Aging and their Associations with Major Depressive Disorder and Inflammatory Markers
Authors: Xu Eileen Y. , Green Claire , McCartney Daniel L. , Han Laura K.M. , Evans Kathryn L. , Walker Rosie M. , Gadd Danni A. , Steele Douglas , Waiter Gordon , Campbell Archie , Lawrie Stephen M. , Cole James H. , McIntosh Andrew M. , Shen Xueyi , Whalley Heather C. 
Published: November 2024

AbstractBackgroundA growing body of evidence suggests that Major Depressive Disorder (MDD) may be associated with premature biological aging. However, most studies have examined brain-based and DNAm-based measures of biological age (BioAge) in isolation. Previous studies also suggest the relevance of inflammation, yet the relationship between MDD, BioAge and inflammation remains unclear.MethodWe investigated two well-studied BioAge measures: BrainAge and DNA methylation age (DNAmAge) in Generation Scotland (GS:STRADL; BrainAge N=1,067; DNAmAge N=684; 26-76 years) and UK Biobank (UKB, BrainAge N=12,018, 45-80 years). Premature brain and DNAm aging was operationalised as ‘Predicted Age Difference’ (Brain-PAD and DNAm-PAD, respectively). We tested individual and additive contributions of Brain-PAD and DNAm-PAD to lifetime/current MDD using logistic regression, followed by exploratory analyses of acute inflammatory biomarkers as mediators of this relationship.ResultsLifetime MDD cases showed significantly higher BrainAge and DNAmAge, ranging from 1.60-2.45 years increase compared to controls; no differences were found for DNAmAgeHorvathor for BrainAge in UKB. Lifetime MDD associated with DNAm-PADGrimAge, DNAm-PADPhenoAgeand Brain-PAD, ranging from β = .22 - .27 (UKB Brain-PAD β = .05). DNAm-PAD and Brain-PAD demonstrated shared and distinctive contributions to lifetime MDD (DNAm-PADPhenoAgeplus Brain-PAD explained maximum variance, AUC=0.69, R2=9%). Six inflammation biomarkers associated with current, but not lifetime MDD; no significant mediation effects were found.ConclusionsOur findings highlight shared and distinct contributions of premature brain and DNAm aging in lifetime MDD. We found no evidence for a mediating role of inflammation, however future work utilizing more stable biomarkers may elucidate potential biological mechanisms.
Description of Patient Characteristics and Clinical and Economic Outcomes of Orthopedic Sutures Used for Rotator Cuff Repair
Authors: Corso Katherine , Smith Caroline , Varughese Biju , Wood James , Ruppenkamp Jill , Putnam Matthew 
Published: November 2024

AbstractBackgroundA better understanding of real-world clinical and economic outcomes associated with orthopedic sutures used for rotator cuff repair is needed.Research Design and MethodsA retrospective, descriptive cohort study using Premier Healthcare Database hospital-based data evaluated patients treated with Dynacord™ or FiberWire®for rotator cuff repair between January 2017-February 2022. Baseline patient characteristics and twelve-month outcomes were assessed. Each suture cohort was analyzed separately. No comparative analyses were performed in this study.ResultsBaseline demographics of 1 074 patients treated with Dynacord™ and 19 899 treated with FiberWire®, respectively, were mean age 59.4, 59.9 years; 59.4% and 58.5% male. All-cause twelve-month hospital revisits were observed in 31.4% and 42.4%, and the incidence proportion with shoulder-related hospital revisits was 12.6% and 14.0%, respectively. The incidence of twelve-month rotator cuff re-repair was 1.2% for Dynacord™ and 1.8% for FiberWire®. Dynacord™ twelve-month all-cause revisit costs (standard deviation [SD]) were $1 649 ($5 870) and $2 230 ($7 204) for FiberWire®. Twelve-month complications, device removals, and manipulations were ≤1% for both cohorts.ConclusionsThis study contributes clinical and economic real-world evidence on two types of orthopedic sutures used for rotator cuff repair.
Trends and Characteristics during 17 Years of Naloxone Distribution and Administration through a Harm Reduction Program in Pittsburgh, Pennsylvania
Authors: Dasgupta Nabarun , Bell Alice , Visnich Malcolm , Doe-Simkins Maya , Wheeler Eliza , Sibley Adams L. , Nocera Maryalice , Seitz Amy E. , Chang Dorothy , Barlow Summer , Dezman Zachary , McAninch Jana 
Published: November 2024

ABSTRACTObjectiveDescribe time trends during 17.6 years of community-based naloxone distribution.MethodsAnalysis of administrative records from a harm reduction program in Pittsburgh, Pennsylvania, USA, collected during encounters for overdose education, naloxone dispensing and refills. Monthly time trends were analyzed using segmented regression. Programmatic context aided interpretation of quantitative findings. We also evaluated impacts of 2014 state legislation loosening naloxone prescribing requirements and providing Good Samaritan protections.ResultsFrom July 2005 to January 2023 there were 16,904 service encounters by 7,582 unique participants, resulting in 70,234 naloxone doses dispensed, with 5,521 overdose response events (OREs), utilizing 8,756 naloxone doses. After legislation, new participants increased from 10.4 to 65.9 per month. New participants tended to be older (46 vs. 37 years), female (58% to 35%), White race, and more likely to be family/friends as opposed to people who use drugs themselves. Consequently, ORE per participant fell from 1.46 to 0.47 in the year after enactment. On average, 1.63 (95% CI: 1.60, 1.65) naloxone doses were administered per ORE, which did not change substantially over 17 years (χ2=0.28, 3 df,p=0.60) during evolution from prescription opioids, to heroin, to illicitly manufactured fentanyl. In 98.0% of OREs the person who experienced overdose “was okay”, i.e., survived. Emergency medical services were called in 16% of OREs overall, but <7% since 2019. There were 106 more emesis events per 1,000 OREs with 4mg nasal spray compared to intramuscular injection; and 48 per 1,000 more reports of anger. Titration of intramuscular naloxone was associated with lower rates of adverse events.ConclusionsWhile state legislation created the environment for expansion, reaching previously underserved communities required intentional new programmatic development and outreach. Long-term consistency of <2 doses per ORE, high survival rate, and robust utilization all lend confidence in prioritizing naloxone distribution directly to people who use drugs and their social networks.
The Role of p16Ink4a as an Early Predictor of Physiological Decline during Natural Aging
Authors: Tang Lingzi , Hladyshau Siarhei , Ross Allison , Nyrop Kirsten A. , Entwistle Amy , Muss Hyman B. , Mitin Natalia , Tsygankov Denis 
Published: November 2024

ABSTRACTCellular senescence is a prominent accomplice of aging. The expression of gene p16ink4a has been established as a biomarker of cellular senescence in humans and animal models. However, it has not been extensively studied in clinical settings in the context of natural aging and the development of age-related diseases. Here, we report the results of a natural aging study that provided an assessment of cellular senescence and a battery of measures of clinical status, quality of life (QOL), and physical performance in 250 community-dwelling participants across age continuum. This report focused on analyzing predictive relationships between cellular senescence and different clinical assessments. Our results suggest that clinical labs and QOL assessments produce distinct groupings of participants, yet both have strong predictive associations with p16ink4a. Furthermore, the highest accuracy of p16ink4a prediction requires subsets of measurements representing diverse aspects of each assessment, pointing towards a system-level role of p16ink4a. Our analysis also led to an assessment-based composite indexes that strongly correlate with p16ink4a expression. Our study underscores p16ink4a’s association with both earlier signs of physiological decline (based on clinical labs) and the later onset of health issues limiting the quality of life.
Estimating the economic burden of stroke among informal caregivers in Australia using Productivity Adjusted Life Year
Authors: Das Neha , Nguyen Dieu , Lee Peter , Robinson Suzanne , Gao Lan 
Published: November 2024

AbstractBackgroundThe Productivity Adjusted Life Year (PALY) metric is a novel measure for exploring the societal impact of health conditions on work productivity. Given that stroke is a major cause of DALYs (disability-adjusted life years) and the crucial role of caregivers in post-stroke care our study aims to quantify the PALY loss associated with stroke caregivers and the impact on their quality of life (QoL) by calculating quality-adjusted life years (QALYs).MethodDynamic life table modeling was used to simulate the follow-up of the Australian working-age population (aged 15–65 years) over 30 years of follow-up (2023-2052 inclusive). The model compared the Australian stroke informal carer group and a hypothetical cohort of non-carers. Key data was obtained from literature and publicly available data. The model was constructed using Microsoft Excel® (Microsoft Corporation, Redmond, WA, US). Labor force participation rates were applied to population estimates to arrive at the approximate number of full-time equivalent (FTE) which was then multiplied by the productivity index and years of life lived (YLL) to estimate PALYs and the utility values were multiplied by YLL to estimate QALYs.ResultsOver a 30-year period, an estimated 35,337 QALYs and 87,773 PALYs and AU$ 19.1 billion were lost due to the health and productivity burden attributed to the provision of informal care for stroke patients. On average, annual informal carer losses were 1,178 QALYs and 2,926 PALYS, corresponding to AU$ 636 million per year in productivity loss.ConclusionOur analyses demonstrate the health and economic consequences of providing care to stroke patients over the forthcoming decades and highlight the need for interventions to reduce the burden of stroke and its impact on caregivers.
Molecular and genetic characterization of sex-linked orange coat color in the domestic cat
Authors: Kaelin Christopher B. , McGowan Kelly A. , Trotman Joshaya C. , Koroma Donald C. , David Victor A. , Menotti-Raymond Marilyn , Graff Emily C. , Schmidt-Küntzel Anne , Oancea Elena , Barsh Gregory S. 
Published: November 2024

AbstractTheSex-linked orangemutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat color genes, there is no apparent homolog forSex-linked orangein other mammals. We show that theSex-linked orangeis caused by a 5 kb deletion that leads to ectopic and melanocyte-specific expression of theRho GTPase Activating Protein 36(Arhgap36) gene. Single cell RNA-seq studies from fetal cat skin reveal that red/yellow hair color is caused by reduced expression of melanogenic genes that are normally activated by the Melanocortin 1 receptor (Mc1r)—cyclic adenosine monophosphate (cAMP)—protein kinase A (PKA) pathway, but theMc1rgene and its ability to stimulate cAMP accumulation is intact. Instead, we show that increased expression ofArhgap36in melanocytes leads to reduced levels of the PKA catalytic subunit (PKAC); thus,Sex-linked orangeis genetically and biochemically downstream ofMc1r. Our findings solve a comparative genomic conundrum, providein vivoevidence for the ability of Arhgap36 to inhibit PKA, and reveal a molecular explanation for a charismatic color pattern with a rich genetic history.
PyEvoCell: An LLM- Augmented Single Cell Trajectory Analysis Dashboard
Authors: Mathur Sachin , Beauvais Mathieu , Giribet Arnau , Barrero Nicolas Aragon , Zhang Chaorui-Tom , Rahman Towsif , Wang Seqian , Huang Jeremy , Nouri Nima , Kurlovs Andre , Bar-Joseph Ziv , Passban Peyman 
Published: November 2024

SummaryMotivationSeveral methods have been developed for trajectory inference in single cell studies. However, identifying relevant lineages among several celltypes is a challenging task and requires deep understanding of various celltype transitions and progression patterns. Therefore, there is a need for methods that can aid researchers in the analysis and interpretation of such trajectories.ResultsWe developed PyEvoCell, a dashboard for trajectory interpretation and analysis that is augmented by large language model (LLM) capabilities. PyEvoCell applies the LLM to the outputs of trajectory inference methods such as Monocle3, to suggest biologically relevant lineages. Once a lineage is defined, users can conduct differential expression and functional analyses which are also interpreted by the LLM. Finally, any hypothesis or claim derived from the analysis can be validated using the veracity filter, a feature enabled by the LLM, to confirm or reject claims by providing relevant PubMed citations.Software Availability and ImplementationThe software is available athttps://github.com/Sanofi-Public/PyEvoCell. It contains installation instructions, user manual, demo datasets, as well as license conditions (including limitation to non-commercial uses only).Supplementary informationSupplementary information is attached.
Undergraduate research project uncovers a novel strain of amphibian chytrid fungus in the Northeastern United States
Authors: York Katharine , Mitchell Mariah , Cardoso Tyler , Chapdelaine Ashley , Song Yuhui , Duryea M. Catherine 
Published: November 2024

AbstractInvestigation of the genetic variation ofBatrachochytrium dendrobatidis(Bdor chytrid fungus) in New Hampshire (NH) in the northeastern U.S. has shown the presence of genetic mutations which are currently undocumented in the literature. DNA was collected as part of a long-term monitoring project in New Hampshire to test for the presence ofBdin amphibian populations. In this monitoring project, we are detecting the presence ofBdin multiple populations, but the observed amphibians do not appear to have increased mortality or other symptoms related to the fungus. To further investigate the strain ofBdaffecting NH amphibians, we sequenced samples that were collected in 2019, as part of your yearly monitoring effort. Utilizing the Basic Local Alignment Search Tool (BLAST) and sequences available on GenBank, we found that there are two different strains of chytrid in the observed NH amphibians. These strains are similar to strains noted previously in New England, but exhibit unique point mutations and in one case, a deletion. These variations could affect the impact thatBdhas on amphibians in this region, and therefore could contribute to a better understanding of the variation in strains of chytrid and how they impact amphibian populations around the world. This study highlights the importance of monitoring efforts conducted at smaller, non-research institutions and we encourage other small institutions to take up similar monitoring efforts forBdor other national or global conservation concerns.
Lagomorph cranial biomechanics and the functional significance of the unique fenestrated rostrum of leporids
Authors: Wood-Bailey Amber P , Sharp Alana C 
Published: November 2024

AbstractThe crania of leporid lagomorphs are uniquely fenestrated, including the posterior cranial bones and the lateral portion of the maxilla. The functional significance of the highly fenestrated rostrum has received considerably little attention, despite being absent in other mammalian herbivores with a long rostrum. This unique feature is of particular interest when considering functional relationships between the loading regime and cranial structure. Two primary hypotheses have been suggested: maxillary fenestrations may be associated with the transmission and redirection of incisal occlusal forces, or fenestrations may reduce skull weight to assist with manoeuvrability and increase running speed. Here we apply a comparative approach using finite element analysis to determine how the overall stress and strain environment is affected by the presence or absence of maxillary fenestrations. We compare three lagomorph species with various degrees of latticing in the fenestrated rostrum, with two macropods that do not have fenestrations. We then produce theoretical models of the three lagomorphs by filling in the fenestrated region. Our results show that the presence of fenestrations makes little difference to the overall stress experienced through the cranium and does not impact the efficiency of incisor biting. This adds to the increasing evidence that features of lagomorph cranial morphology correlate with locomotor demands, adapting to loads other than mastication. Modulating cranial mass with fenestrations may provide benefits of a lighter skull, while still providing enough surface area for muscle attachments.