bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual reality as a strategy for intra-operatory anxiolysis and pharmacological sparing in patients undergoing breast surgeries: the V-RAPS randomized controlled trial protocol
Authors: Zako Joe , Daccache Nicolas , Burey Julien , Clairoux Ariane , Morisson Louis , Laferrière-Langlois Pascal
Published: November 2024

Introduction

Virtual reality (VR) has increasingly found applications beyond leisure and video games, extending into the field of medicine. Recent studies indicate that VR can effectively reduce anxiety and pain in pediatric patients undergoing uncomfortable medical procedures, such as burn wound care. Yet, VR use in the operating room is still rare, despite a growing trend toward regional anesthesia without general anesthesia; physicians still frequently rely on pharmacological sedation to manage procedural anxiety. By leveraging VR’s anxiolytic properties, it may be possible to decrease the need for intravenous (IV) sedation which is associated with risk of adverse events like apnea and hypoxemia and delayed recovery.

Objectives

This study’s main objective is to explore the impact of VR on IV sedation requirements in adult patients undergoing breast surgery under paravertebral (PV) block without general anesthesia. We hypothesize that VR immersion will reduce the need for intraoperative pharmacological sedation. Secondary objectives include assessing the tolerance of patients to the VR headset, examining the impact of the chosen VR scenario on the primary outcome, evaluating the incidence of adverse effects, measuring patient satisfaction, and analyzing the output of the Nociception Level (NOL) Index among awake surgical patients.

Material and methods

This single center randomized controlled trial will enroll 100 patients aged 18 or above undergoing breast surgery under PV block. Participants will be randomly allocated to the VR group or the control group; both will have access to pharmacological sedation through patient-controlled sedation (PCS). Participants in the VR group will choose between three different VR scenarios and will be allowed to switch between these scenarios during surgery. The primary outcome will be the time-adjusted and weight adjusted dose of self-administered intraoperative propofol. Secondary outcomes will include patient satisfaction, adverse events, and post-anesthesia care unit length of stay (PACU LOS).

Ethics

This trial has been approved by the regional ethics committee (Comité d’Éthique de la Recherche du CIUSSS de l’Est de l’Île de Montréal) on September 9th, 2024.

Trial registration

ClinicalTrials.gov (July 25th, 2024). Unique protocol ID: 2025-3802. Trial identification number:NCT06522711.
Denoising diffusion model for increased performance of detecting structural heart disease
Authors: Streiffer Christopher D. , Levin Michael G. , Witschey Walter R. , Anyanwu Emeka C.
Published: November 2024

Recent advancements in generative artificial intelligence have shown promise in producing realistic images from complex data distributions. We developed a denoising diffusion probabilistic model trained on the CheXchoNet dataset, encoding the joint distribution of demographic data and echocardiogram measurements. We generated a synthetic dataset skewed towards younger patients with a higher prevalence of structural left ventricle disease. A diagnostic deep learning model trained on the synthetic dataset performed comparably to one trained on real data producing an AUROC=0.75(95%CI 0.72-0.77), with similar performance on an internal dataset. Combining real data with positive samples from the synthetic data improved diagnostic accuracy producing an AUROC=0.80(95%CI 0.78-0.82). Subgroup analysis showed the largest performance improvement across younger patients. These results suggest diffusion models can increase diagnostic accuracy and fine-tune models for specific populations.
Home-based transcranial direct current stimulation for major depressive disorder: 6-month follow-up from a randomised sham-controlled trial
Authors: Woodham Rachel D. , Selvaraj Sudhakar , Lajmi Nahed , Hobday Harriet , Sheehan Gabrielle , Ghazi-Noori Ali-Reza , Lagerberg Peter J. , Machado-Vieira Rodrigo , Soares Jair C. , Young Allan H. , Fu Cynthia H.Y.
Published: November 2024

Transcranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our randomised controlled trial, a fully remote, 10-week course of home-based active tDCS showed greater clinical efficacy as compared to sham tDCS in a double-blind randomised controlled trial (RCT). tDCS was administered at 2mA for 30-minute sessions in a bifrontal montage with anode over the left dorsolateral prefrontal cortex (DLPFC) and cathode over the right DLPFC. Following the 10-week blinded trial, all participants could receive active tDCS in a 10-week open label phase. Participants who had completed the open-label treatment were invited for additional long term follow-up visits over 6 months. Participants were allowed to keep their tDCS device and could choose to continue stimulation during the follow-up period. In the follow-up phase, 42 participants (27 women) attended at least one visit. Ongoing use of the tDCS device was 59% at 3 months and 55% at 6 months during the follow-up period. The clinical response rate was 64% at 3 months and 76% at 6 months. Participants who had shown a clinical response after open label treatment maintained a response rate of 90% at 6 months. In summary, high rates of clinical response were maintained in 6-month follow-up whether or not participants continued to use the tDCS device.
Blood glucose dynamics vary with economic provenance of meal
Authors: Hamill Daniel , Smith Trenton G. , Venn Bernard
Published: November 2024

The 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

Background

Long-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.

Methods

We 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.

Results

The 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.

Conclusion

Knowledge 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

Purpose

Sepsis, 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.

Methods

We 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.

Results

Our 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.

Conclusions

This 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

Introduction

9663 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 methods

A 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 dissemination

This 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

Background

A 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.

Method

We 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.

Results

Lifetime 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.

Conclusions

Our 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

Background

A better understanding of real-world clinical and economic outcomes associated with orthopedic sutures used for rotator cuff repair is needed.

Research Design and Methods

A 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.

Results

Baseline 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.

Conclusions

This 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

Objective

Describe time trends during 17.6 years of community-based naloxone distribution.

Methods

Analysis 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.

Results

From 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.

Conclusions

While 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

Cellular 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

Background

The 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).

Method

Dynamic 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.

Results

Over 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.

Conclusion

Our 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

TheSex-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

Motivation

Several 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.

Results

We 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 Implementation

The 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 information

Supplementary 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

Investigation 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

The 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.
Loss of neuronal Imp induces seizure behavior through Syndecan function
Authors: Roy Paula R. , Link Nichole
Published: November 2024

Seizures affect a large proportion of the global population and occur due to abnormal neuronal activity in the brain. Unfortunately, widespread genetic and phenotypic heterogeneity contribute to insufficient treatment options. It is critical to identify the genetic underpinnings of how seizures occur to better understand seizure disorders and improve therapeutic development. We used theDrosophilamodel to identify that IGF-II mRNA Binding Protein (Imp) is linked to the onset of this phenotype. Specific reduction of Imp in neurons causes seizures after mechanical stimulation. Importantly, gross motor behavior is unaffected, showing Imp loss does not affect general neuronal activity. Developmental loss of Imp is sufficient to cause seizures in adults, thus Imp-modulated neuron development affects mature neuronal function. Since Imp is an RNA-binding protein, we sought to identify the mRNA target that Imp regulates in neurons to ensure proper neuronal activity after mechanical stress. We find that Imp protein bindsSyndecan(Sdc) mRNA, and reduction of Sdc also causes mechanically-induced seizures. Expression of Sdc inImpdeficient neurons rescues seizure defects, showing that Sdc is sufficient to restore normal behavior after mechanical stress. We suggest that Imp protein bindsSdcmRNA in neurons, and this functional interaction is important for normal neuronal biology and animal behavior in a mechanically-induced seizure model. Since Imp and Sdc are conserved, our work highlights a neuronal specific pathway that might contribute to seizure disorder when mutated in humans.
Distinct immune responses to HIV and CMV in Hofbauer cells across gestation highlight evolving placental immune dynamics
Authors: Schuch Viviane , Hossack Daniel , Hailstorks Tiffany , Chakraborty Rana , Johnson Erica L.
Published: November 2024

Placental immune responses to Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (CMV) vary across gestational stages and may influence postnatal outcomes. This study investigates the innate immunity of Hofbauer cells from placentae obtained at early/mid-gestation (18–21.6 weeks) and term (>37 weeks). RNA sequencing and cytokine profiling reveal that early/mid-gestation HCs exhibit heightened differential gene expression responses compared to term HCs, indicating a distinct transcriptional activity in early pregnancy. Significant overlap in gene expression profiles of early/mid-gestation cells in response to CMV and HIV suggest similar innate immune responses, while term cells exhibit distinct patterns, reflecting the temporal evolution of placental immunity. Integration with Human Protein Atlas database reveals more placental-specific differentially expressed genes in early/mid-gestation HCs exposed to HIV and CMV compared to term cells. Functional analysis reveals downregulation of pathways related to oxygen stress, estrogen response, and KRAS signaling pathway in early/mid-gestation HCs, with HIV uniquely upregulating reactive oxygen species and CMV uniquely disrupting WNT β-Catenin signaling. In term HCs, CMV exposure upregulates antiviral interferon (IFN) signaling and inflammatory pathways. Co-expression analysis highlights distinct molecular pathway enrichments across gestation, particularly with upregulation of IFN signaling and disruption of lipid metabolism in term CMV-exposed HCs. Cytokine profiling shows enhanced expression of GM-CSF, IFN-γ, and Th2-associated cytokines in early/mid-gestation HCs, indicating heightened immune responsiveness. These findings reveal the dynamic nature of placental immunity and underscore the need for targeted interventions to address unique immune and metabolic disruptions caused by viral infections at distinct stages of pregnancy to improve fetal and infant health outcomes.
Variable phylosymbiosis and cophylogeny patterns in wild fish gut microbiota of a large subtropical river
Authors: Liu Yaqiu , Liu Xinhui , Kormas Konstantinos Ar. , Li Yuefei , Li Huifeng , Li Jie
Published: November 2024

The persistence and specificity of fish host-microbial interaction during evolution is an important part of exploring the host-microbial symbiosis mechanism. However, it remains unclear how the environmental and host factors shape fish host-microbe symbiotic relationship in subtropical rivers with complex natural environments. Freshwater fish are important consumers in rivers and lakes and considered keystone species in maintaining the stability of food webs there. In this study, patterns and mechanisms shaping gut microbiota community in 42 fish species from the Pearl River, in the subtropical zone of China were investigated. The results showed that fish host specificity is key driver of gut microbiota evolution and diversification. Different taxonomic levels of host showed different degrees of contribution in gut microbiota variation. Geographical location and habitat type were the next most important factors in shaping gut microbiota across the 42 fishes, followed by diet and gut trait. Our results emphasized the contribution of stochastic processes (drift and homogenizing dispersal) in the gut microbial community assembly of freshwater fishes in the middle and lower reach of the Pearl River. Phylosymbiosis is evident at both global and local levels, which are jointly shaped by complex factors including ecological or host physiological filtration and evolutionary process. The core microbiota showed co-evolutionary relationships of varying degrees with different taxonomic groups. We speculate that host genetic isolation or habitat variation facilitate the heterogeneous selection (deterministic process), which occurs and results in different host-core bacterium specificity.
Characterizing 3D RNA structural features from DMS reactivity
Authors: Sanduni Deenalattha D. H. , Jurich Chris P. , Lange Bret , Armstrong Darren , Nein Kaitlyn , Yesselman Joseph D.
Published: November 2024

Dimethyl sulfate (DMS) chemical mapping probes RNA structure, where low reactivity is generally interpreted as Watson-Crick (WC) base pairs and high reactivity as unpaired nucleotides. Studies examining DMS reactivity of RNAs with known 3D structures have identified nucleotides that deviate from this interpretation with distinct solvent accessibility and hydrogen bonding patterns. Understanding the frequency of these outliers and their recurring structural 3D features remains incomplete. To address this knowledge gap, we systematically analyzed DMS reactivity patterns across a library of 7,500 RNA constructs containing two-way junctions with known 3D structures. We observe DMS reactivity exists on a continuum over four orders of magnitude with approximately 10% overlap in reactivity between WC and non-WC nucleotides. We find that non-WC bases with WC-like DMS protection exhibit increased hydrogen bonding and decreased solvent accessibility, whereas WC pairs exhibiting greater DMS reactivity tend to flank junctions, correlating with weaker base stacking and greater junction dynamics. Furthermore, we discover that DMS reactivity values in non-canonical pairs correlate with atomic distances and base pair geometry, enabling discrimination between different 3D conformations. These DMS reactivity patterns indicate that DMS reactivity provides atomic-scale information about RNA 3D conformations, which can be used to model RNA structures and dynamics.
HiC2Self: self-supervised denoising for bulk and single-cell Hi-C contact maps
Authors: Yang Rui , Karbalayghareh Alireza , Leslie Christina S.
Published: November 2024

Abstract

Hi-C is a chromosome conformation capture assay used to study 3D genome organization. The recent development of single-cell Hi-C technologies has further enabled the examination of 3D chromatin organization in individual cells, although these approaches often suffer from low-coverage libraries and data sparsity. Here we introduce HiC2Self, a self-supervised framework for denoising Hi-C contact maps that requires only low-coverage data as input. HiC2Self not only reconstructs key structures (such as TADs and significant loops) from bulk libraries, but its self-supervised training framework also allows it to easily reconstruct cell-type-specific Hi-C structures without the generalization challenges faced by supervised models. HiC2Self can also accurately reconstruct significant loops from Micro-C data at 1 kb resolution. Moreover, when applied to single-nucleus methyl-3C data, HiC2Self successfully reconstructs local TAD structures around specific genes at 10 kb resolution with as few as 50 cells. Finally, HiC2Self enables the examination of single-cell structures at 50 kb resolution in individual cells of the same cell type. HiC2Self thus provides a general tool for denoising bulk, pseudo-bulk, and single-cell 3D contact maps to enable downstream analyses.
Group 2 and 3 ABC-transporter dependant capsular K-loci contribute significantly to variation in the invasive potential ofEscherichia coli
Authors: Gladstone Rebecca A. , Pesonen Maiju , Pöntinen Anna K. , Mäklin Tommi , MacAlasdair Neil , Thorpe Harry , Shao Yan , Mallawaarachchi Sudaraka , Arredondo-Alonso Sergio , Parcell Benjamin J. , Turnbull Jake David , Tonkin-hill Gerry , Johnsen Pål J. , Samuelsen Ørjan , Thomson Nicholas R. , Lawley Trevor , Corander Jukka
Published: November 2024

The major opportunistic pathogenEscherichia coliis the largest cause of antimicrobial resistance (AMR) associated infections and deaths globally. Considerable antigenic diversity has been documented in Extra-intestinal pathogenicE. coli(ExPEC). Still, the need for systematic genomic surveys of asymptomatic colonisation and invasive disease has precluded the quantification of K-type invasive potential across different ExPEC lineages. We assembled and curated anin-silicocapsular typing database for group 2 and group 3 K-loci from >20,000 genomes and applied it to paired carriage and disease cohorts to investigate K-type epidemiology. The most virulent circulating capsules have estimated odds ratios of >10 for being found in bloodstream infections versus carriage. The invasive potential differed markedly between lineages, and subclades of the global multi-drug resistant ST131, which displayed limited O and H antigens but substantial K-type diversity. We also discovered that insertion sequence elements contribute to the evolutionary dynamics of group 2 and group 3 K-loci by importing new capsular genes. Furthermore, the level of capsule diversity was positively correlated with more recombinogenic lineages that could adapt their antigenic repertoire faster. Our investigation highlights several K-types and lineages that contribute disproportionately to invasive ExPEC disease, which are associated with high levels of AMR. These results have significant translational potential, including improved ExPEC diagnostics, personalised therapy options, and the ability to build predictive regional risk maps by combining genomic surveys with demographic and patient frailty data.
Disparities in Anti-emetic Prophylaxis Care Processes are Predicted by Patient Neighborhood: A Retrospective Cohort and Geospatial Analysis
Authors: Han Jiuying , Wan Neng , Jacobson Cameron K. , Pace Nathan L. , Kartchner Cade K. , Hohl Alexander S. , Schonberger Robert B. , Colquhoun Douglas A. , Dutton Richard P. , Andreae Michael H. , Pearson John F.
Published: November 2024

Background

Social Determinants of Health (SDoH) continue to drive persistent disparities in perioperative care. Our team has previously demonstrated racial and socioeconomic disparities in perioperative processes, notably in the administration of antiemetic prophylaxis, in several large perioperative registries. Given how neighborhoods are socially segregated in the US, we examined geospatial clustering of perioperative antiemetic disparities.

Methods

We conducted a retrospective cohort study of anesthetic records from the University of Utah Hospital with 19,477 patients meeting inclusion criteria. We geocoded patient home addresses and combined them with the Census Block Group(CBG) level neighborhood disadvantage (ND), a composite index of from the National Neighborhood Data Archive (NaNDA). We stratified our patients by antiemetic risk score and calculated the number of anti-emetic interventions. We utilized Poisson Spatial Scan Statistics, implemented in SaTScan, to detect geographic clusters of under-treatment.

Results

We identified one significant cluster (p < .001) of undertreated perioperative antiemetic prophylaxis cases. The relative risk (RR) of the whole cluster is 1.44, implying that patients within the cluster are 1.44 times more likely to receive fewer antiemetics after controlling for antiemetic risk. Patients from more disadvantaged neighborhoods were more likely to receive below median antiemetic prophylaxis after controlling for risk.

Conclusions

To our knowledge, this is the first geospatial cluster analysis of perioperative process disparities; we leveraged innovative geostatistical methods and identified a spatially defined, geographic cluster of patients whose home address census-tract level neighborhood deprivation index predicted disparities in risk adjusted antiemetic prophylaxis.
Cost-effectiveness Analysis of Alternative Infant and Neonatal Rotavirus Vaccination Schedules in Malawi
Authors: Wenger Catherine , Asare Ernest O. , Kwon Jiye , Li Xiao , Mwinjiwa Edson , Chinkhumba Jobiba , Jere Khuzwayo C. , Hungerford Daniel , Cunliffe Nigel A. , Paltiel A. David , Pitzer Virginia E.
Published: November 2024

Rotavirus is the leading cause of severe diarrhea among children under five worldwide, especially in low- and middle-income countries (LMICs). Although vaccination is the best strategy for preventing rotavirus infection, obstacles leading to poor vaccine effectiveness undermine its impact in LMICs. This study aimed to evaluate the impact and cost-effectiveness of the current two-dose Rotarix vaccine schedule in Malawi compared to two alternative vaccine delivery schedules and a next-generation neonatal vaccine (RV3-BB) from 2025-2034. The cost-effectiveness of rotavirus vaccine strategies in Malawi was evaluated from both the government and societal perspectives using estimates of moderate-to-severe and non-severe rotavirus cases derived from a mathematical model of rotavirus transmission dynamics and published estimates of health-seeking behaviors and costs as inputs. A probabilistic sensitivity analysis was performed to evaluate the robustness of our results to parameter uncertainty. Over a ten-year time horizon, the current two-dose strategy was predicted to avert over 1.5 million cases and 90,000 disability-adjusted life-years (DALYs) and cost $104.87 per DALY averted compared to no vaccination from the government perspective. Adding a third dose at 14 weeks could avert about 1 million more cases and cost $5 million more than the current strategy. The neonatal RV3-BB vaccine could avert 1.1 million cases and 41,000 DALYs due to rotavirus and save about $3.7 million compared to the current strategy. The current rotavirus vaccine program in Malawi is cost-effective and saves lives compared to no vaccination. However, adding a third dose is likely to be cost-effective at a willingness to pay (WTP) of $138.38 per DALY averted, while switching to the neonatal RV3-BB vaccine when available is likely to be cost-effective at a WTP above $45.89 per DALY averted.
Knowledge, attitude, and practices of reporting adverse events following immunization among healthcare providers in Simiyu Region, Tanzania: A cross sectional study
Authors: Kambona Raphael C. , Marealle Alphonce I. , Kilonzi Manase , Masunga Emmanuel , Kunambi Peter , Ilomo Helfrid B. , Mutagonda Ritah
Published: November 2024

Introduction

Immunization is the most cost effective health intervention in the history of mankind. Its role in reducing the morbidities and mortality due to vaccine-preventable diseases is significant. Despite vaccines being important in saving lives; adverse events following immunization (AEFI) do occur that need prompt detection, management, and then reported, analyzed, and the findings being shared with all stakeholders to ensure vaccine safety. The reporting of AEFI in Tanzania is still low. Health Care Providers (HCPs) are obliged to collect and report AEFI. This study assessed the knowledge, attitude, and practices of reporting AEFI among HCPs in Simiyu region, Tanzania.

Methodology

This cross-sectional study was conducted between May and June 2024. A total of 180 HCPs were enrolled, structured questionnaire was used to assess the knowledge, attitude, and practices of reporting AEFI among HCPs at primary health facilities. Statistical Package for Social Science (SPSS) was used for entry and data analysis, and the findings were summarized using frequency and percentages. Chi-square test was used to screen for factors associated with AEFI reporting while Poisson regression model was used to confirm the determinants.

Results

The median age of study participants was 32 (Inter Quartile Range; 29, 38) years. Among the HCPs, more than one quarter (28.89%) had adequate knowledge of reporting AEFI, and more than half (68.89%) had positive attitudes and good practices (62.22%) of reporting AEFI. Less than half of HCPs (48.3%) had encountered AEFI cases, and about two-thirds (69%) reported it.

Conclusions and recommendations

Despite the inadequacy of knowledge on reporting AEFI among HCPs, the attitude and practices of reporting AEFI among HCPs were promising. Based on the study findings, we recommend more training on vaccine surveillance, routine follow-up, and supportive supervision of AEFI surveillance for optimal AEFI reporting and vaccine safety surveillance in Tanzania.
How early family activities predict life satisfaction among parents with adult children
Authors: Peterson M. Nils , Bordewieck Kathleen , Velluti-Fry Elijah , Jansson Julia L. , Peterson Gwen E. , Peterson Tarla R.
Published: November 2024

Life satisfaction represents a relatively universal social goal. Research suggests familiar interactions of diverse types may shape life satisfaction, but many questions remain about the valence and relative importance of variables shaping life satisfaction. In this exploratory study, we examined the relationships between frequency of shared parent-child activities in early life stages and self-reported parental life-satisfaction after children leave home using a case study of NC State University and University of Texas at El Paso students’ parents (n=92). Frequency of shared housework with young children was the most important, and positive, predictor of life satisfaction among parents after the children left home, and shared religious activities were also a positive predictor. Conversely, frequency of playing sports with young children was a negative predictor of later life satisfaction among parents. We did not detect a relationship for shared visits to local parks. Current activity level and income level both positively predicted life satisfaction, but we did not detect relationships for gender or marital status. This preliminary research highlights several novel ways shared family activities may affect later life satisfaction among older parents, but requires larger scale research to assess if an how findings apply in other contexts.