bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Venous Thromboembolism Is Common Following Acute Necrotizing Pancreatitis and Is Associated With Worse Clinical Outcomes
Authors: Singh Ritu R. , Thandassery Ragesh B. , Chawla Saurabh 
Published: May 2024

Objectives
Although splanchnic vein thrombosis (SVT) is a well-known local complication of acute pancreatitis, extrasplanchnic venous thromboembolism (ESVT) is inadequately studied. Here, we aim to explore the incidence of venous thromboembolism (VTE) in acute necrotizing pancreatitis (ANP) and the associated mortality.

Methods
Adults with a diagnosis of ANP from January 2017 to December 2022 were identified using appropriate International Classification of Diseases, 10th Revision, Clinical Modification codes. The primary outcome was development of acute ESVT within 1 month of ANP. Secondary outcomes were 90-day mortality, 30-day rehospitalization, and oral anticoagulant (OAC) use in patients with ESVT. Propensity score matching (1:1) was performed for baseline characteristics and common comorbidities.

Results
During the study period, 17,942 (7.11%) patients were diagnosed with ANP, and about 10% (1,737) of them had a diagnosis of ESVT. Of all VTEs, 61% were ESVT with or without SVT, and 63% (n = 1799) were SVT. Ninety-day mortality (16.3% vs 5.7%; risk ratio [RR], 2.86; 95% confidence interval, 2.29–3.56) and 30-day rehospitalization (31% vs 19%; RR, 1.63; 95% confidence interval, 1.49–1.79) were higher in patients with ESVT compared with non-VTE patients. Sixty percent of patients with ESVT were on OAC, and OAC use was associated with lower 90-day mortality (8.9% vs 19.4%; RR, 0.46) without increased risk of adverse events (acute gastrointestinal bleeding, intracranial bleeding, or need for transfusion).

Conclusions
Systemic VTE is common in patients with ANP and may contribute to increased mortality and risk of readmissions. Prospective studies can confirm our findings and explore the role of aggressive VTE prophylaxis in patients with ANP during hospital stay and in the immediate ambulatory period.
Differential Effects of Ganglioside Lipids on the Conformation and Aggregation of Islet Amyloid Polypeptide
Authors: McCalpin Samuel D. , Mechakra Lina , Ivanova Magdalena I. , Ramamoorthy Ayyalusamy 
Published: May 2024

ABSTRACTDespite causing over 1 million deaths annually, Type 2 Diabetes (T2D) currently has no curative treatments. Aggregation of the islet amyloid polypeptide (hIAPP) into amyloid plaques plays an important role in the pathophysiology of T2D and thus presents a target for therapeutic intervention. The mechanism by which hIAPP aggregates contributes to the development of T2D is unclear but are proposed to involve disruption of cellular membranes. However, nearly all research on hIAPP-lipid interactions has focused on anionic phospholipids, which are primarily present in the cytosolic face of plasma membranes. We seek here to characterize the effects of three gangliosides, the dominant anionic lipids in the outer leaflet of the plasma membrane, on the aggregation, structure, and toxicity of hIAPP. Our results show a dual behavior that depends on the molar ratio between the gangliosides and hIAPP. For each ganglioside, a low lipid:peptide ratio enhances hIAPP aggregation and alters the morphology of hIAPP fibrils, while a high ratio eliminates aggregation and stabilizes an α-helix-rich hIAPP conformation. A more negative lipid charge more efficiently promotes aggregation, and a larger lipid headgroup improves inhibition of aggregation. hIAPP also alters the phase transitions of the lipids, favoring spherical micelles over larger tubular micelles. We discuss our results in the context of available lipid surface area for hIAPP binding and speculate on a role for gangliosides in facilitating toxic hIAPP aggregation.
Early male and female footprints of modern humans across Eurasia and Australasia
Authors: Cabrera Vicente M. 
Published: May 2024

ABSTRACTAs an alternative to a recent coastal southern route followed by modern humans to colonize Eurasia after an Out of Africa around 60 Kya, and under the premise that the evolutionary rate based coalescent ages slowdown going backwards in time, I propose a new model based on phylogenetic and phylogeographic analyses of uniparental markers in present and past modern human populations across Eurasia and Australasia.The archaeological record favors a northern route that reached China around 120 kya and then descended latitudinally reaching Southeast Asia and islands around 70-60 kya. These ages coincide with the basal split of the mtDNA macrohaplogroup L3’4* and the origin of the Y-chromosome macrohaplogroup CT* and the subsequent splits in Eurasia of mtDNA haplogroups M and N and Y-chromosome C, D and F clades respectively.Roughly at the same time modern humans arrived in Australasia other groups retreated southwest returning to Africa carrying with them mtDNA L3 and Y-Chromosome E lineages.Southeast Asia and Southwest-Central Asia were the subsequent demographic centers for the respective colonization of East and northern Asia and Europe. Across the Ganges-Brahmaputra and the Indus valleys, South Asia was colonized from both migratory centers.
Kinetic Diagram Analysis: A Python Library for Calculating Steady-State Observables of Biochemical Systems Analytically
Authors: Awtrey Nikolaus Carl , Beckstein Oliver 
Published: May 2024

AbstractKinetic diagrams are commonly used to represent biochemical systems in order to study phenomena such as free energy transduction and ion selectivity. While numerical methods are commonly used to analyze such kinetic networks, the diagram method by King, Altman and Hill makes it possible to construct exact algebraic expressions for steady-state observables in terms of the rate constants of the kinetic diagram. However, manually obtaining these expressions becomes infeasible for models of even modest complexity as the number of the required intermediate diagrams grows with the factorial of the number of states in the diagram. We developedKinetic Diagram Analysis(KDA), a Python library that programmatically generates the relevant diagrams and expressions from a user-defined kinetic diagram.KDAoutputs symbolic expressions for state probabilities and cycle fluxes at steady-state that can be symbolically manipulated and evaluated to quantify macroscopic system observables. We demonstrate theKDAapproach for examples drawn from the biophysics of active secondary transmembrane transporters. For a generic 6-state antiporter model, we show how the introduction of a single leakage transition reduces transport efficiency by quantifying substrate turnover. We applyKDAto a real-world example, the 8-state free exchange model of the small multidrug resistance transporter EmrE of Hussey et al (J General Physiology152(2020), e201912437), where a change in transporter phenotype is achieved by biasing two different subsets of kinetic rates: alternating access and substrate unbinding rates.KDAis made available as open source software under the GNU General Public License version 3.
A viral vaccine design harnessing prior BCG immunization confers protection against Ebola virus
Authors: Ng Tony W. , Furuyama Wakako , Wirchnianski Ariel S. , Saavedra-Ávila Noemí A. , Johndrow Christopher T. , Chandran Kartik , Jacobs William R. , Marzi Andrea , Porcelli Steven A. 
Published: May 2024

AbstractPrevious studies have demonstrated the efficacy and feasibility of an anti-viral vaccine strategy that takes advantage of pre-existing CD4+helper T (Th) cells induced byMycobacterium bovisbacille Calmette-Guérin (BCG) vaccination. This strategy uses immunization with recombinant fusion proteins comprised of a cell surface expressed viral antigen, such as a viral envelope glycoprotein, engineered to contain well-defined BCG Th cell epitopes, thus rapidly recruiting Th cells induced by prior BCG vaccination to provide intrastructural help to virus-specific B cells. In the current study, we show that Th cells induced by BCG were localized predominantly outside of germinal centers and promoted antibody class switching to isotypes characterized by strong Fc receptor interactions and effector functions. Furthermore, BCG vaccination also upregulated FcγR expression to potentially maximize antibody-dependent effector activities. Using a mouse model of Ebola virus (EBOV) infection, this vaccine strategy provided sustained antibody levels with strong IgG2c bias and protection against lethal challenge. This general approach can be easily adapted to other viruses, and may be a rapid and effective method of immunization against emerging pandemics in populations that routinely receive BCG vaccination.
Identification of Respiratory Diseases using Peak Energy Analysis of Acoustic Cough
Authors: Chandy Sujith Thomas , Thangakunam Balamugesh , Rudraraju Gowrisree , Sripada Narayana Rao , Govindaraj Jayanthy , Gottipulla Charishma , Mamidgi Baswaraj , Palreddy Shubha Deepti , Bhoge Nikhil kumar Reddy , Narreddy Harsha Vardhan Reddy , P Prasanna Samuel , Christopher Devasahayam Jesudas , Yechuri Venkat 
Published: May 2024

AbstractBackground and ObjectivesCough is a common symptom of respiratory diseases and change in the cough sound can reflect a pathological condition in the lungs. Recent advancement on the analysis of the cough sound has suggested that it has the potential to be used as a non-invasive marker for screening respiratory conditions, such as Asthma, Chronic Pulmonary Obstructive Disease (COPD), Interstitial Lung Disease (ILD) and Bronchiectasis. The energy envelope is distinguishable for normal subjects versus subjects with respiratory conditions. Peak analysis of the energy envelope helps in quantifying the feature variation for these conditions.This study provides the variation of the peak energy features on the Root Mean Square Energy (RMSE) envelope of cough sounds using machine learning tools. Peak properties of energy contours like peak height, peak prominence, base distance (distance between left and right base of a peak) help in quantifying cough patterns.Methods and MaterialsPatients presenting with respiratory symptoms to the hospital were recruited to the study. Their cough sounds were recorded through a mobile application. The cough sounds were labeled with corresponding pathologies from spirometry. From every subject three audio recordings were collected before taking a spirometry test. Peak analysis is performed on the features extracted from cough audio signals. Peak features are extracted using the function “scipy.signal.find_peaks” from python’s Scipy library. The comparison of these features are done against the clinical diagnosis which the physician finally arrives at after going through the history, spirometry and radiology as per the standard of practice.ResultsThe peak analysis in Asthma shows higher base distance and peak height than that of Normal because of prolonged expulsion and airways constriction. The base distance is observed high in Bronchiectasis but peak height and prominence are less when compared with Normal due to loss of elasticity in the airways. Whereas in COPD the base distance and prominence are found to be less than Normal, Asthma and Bronchiectasis which is attributed to multiple narrowing of the glottis. Additionally, the energy peak heights of the cough were observed to be very close due to conditions like excess mucus, airways inflammation, destruction of lung tissue in COPD.ConclusionPeak analysis of cough provides inferences which can be used as descriptors to differentiate coughs related to respiratory diseases. This study helps us to enhance the performance of Machine Learning models by including the peak energy related features. This peak analysis along with frequency spectral analysis can also be further used in detecting other respiratory conditions.
Unveiling the role of mosquito and human diel activity patterns in the risk of mosquito-borne disease infection
Authors: Ventura Paulo C. , Wilke Andre B.B. , Chitturi Jagadeesh , Kummer Allisandra G. , Agrawal Snigdha , Vasquez Chalmers , Gonzalez Yaziri , Litvinova Maria , Mutebi John-Paul , Ajelli Marco 
Published: May 2024

AbstractBackgroundMosquito-borne pathogens are transmitted through bites of female mosquito vectors that are actively seeking hosts for a blood meal and hosts, when either of them is infectious. Different mosquito species have different preferences for the time of the day/night when they actively seek blood meals. In the United States, the encounters between mosquito vectors and human hosts primarily take place outdoors. Socioeconomic factors such as occupation and income are major determinants of the hour of the day and total amount of time spent outdoors by different population groups. The aim of this study is to quantify: i) diel variations in the level of human exposure to mosquito vectors, and ii) exposure heterogeneities by human population group.MethodsWe collected both diel activity data for two mosquito vector species (Aedes aegyptiandCulex quinquefasciatus) and time-use data for the United States. Then, we analyzed the diel overlap between the two at the population level and by human population group.ResultsFor both mosquito species, we found a substantial heterogeneity in their diel overlap with human outdoors activities. We estimated that the time periods with the highest risk of exposure to bites ofAe. aegyptiare 7am-11am and 5pm-8pm, while the highest risk forCx. Quinquefasciatusis 6am-7am and 6pm-9pm. Moreover, we found disparities in the exposure to mosquito vector species across different demographic groups. Workers with primarily outdoor occupations, males, and Hispanics/Latinos were shown to have higher levels of exposure as compared to the general population. In particular, we estimated that workers with primarily outdoor occupations were 7.50-fold (95%CI: 7.18-7.84) and 6.63-fold (95%CI: 6.09-7.35) more exposed toAe. aegyptiandCx. quinquefasciatusthan the general population, respectively.ConclusionThis study serves as a steppingstone to quantify the risk of exposure to mosquito vector species in the United States. The obtained results can be instrumental for the design of public health interventions such as education campaigns, which could contribute to improve health and health equity.
Gray matter morphology and pain-related disability in young adults with low back pain
Authors: Armour Smith Jo , Tain Rongwen , Chrisman Isaac , Sharp Kelli G. , Glynn Laura M , Van Dillen Linda R. , Jacobs Jesse V. , Cramer Steven C. 
Published: May 2024

ABSTRACTStructural neuroplasticity in the brain may contribute to the persistence of low back pain (LBP) symptoms and the disability associated with them. It is not known if structural adaptations are evident early in the lifespan in young adults with LBP. This study compared gray matter in cortical sensorimotor regions in young adults with and without persistent LBP and identified gray matter and clinical predictors of pain-related disability. Eighty-two individuals with and without a history of LBP participated. Peak and average gray matter density in cortical sensorimotor regions of interest was quantified using voxel-based morphometry. Pain-related disability, pain intensity, pain duration, and pain-related fear were also assessed. Multiple linear regression was used to determine independent predictors of pain-related disability. We document significantly greater peak gray matter density in individuals with LBP in the primary somatosensory cortex, angular gyrus, and the midcingulate cortex. Pain-related disability positively correlated with average gray matter density in the posterior cingulate cortex. The most robust predictors of disability were average gray matter in the posterior cingulate, pain intensity, and pain-related fear. We demonstrate that in young adults, persistent LBP, and pain-related disability, are linked with structural neuroplasticity in regions forming part of the brain network termed the pain matrix. In contrast with studies of LBP in older adults, our findings of increased rather than decreased gray matter in young adults with LBP suggest that gray matter may increase initially in response to nociceptive pain.
Modeling disease progression in spinocerebellar ataxias
Authors: Georgii Elisabeth , Klockgether Thomas , Jacobi Heike , Schmitz-Hubsch Tanja , Ashizawa Tetsuo , Kuo Sheng-Han , Elter Tim , Piraud Marie ,   ESMI study group,   EUROSCA study group,   RISCA study group,   CRC-SCA study group,   SCA-Registry study group, Faber Jennifer 
Published: May 2024

AbstractBackground and objectivesThe most common autosomal-dominantly inherited spinocerebellar ataxias (SCA), SCA1, SCA2, SCA3 and SCA6, account for more than half of all SCA families. Disease course is characterized by progressive ataxia and additional neurological signs. Each of these SCAs is caused by a CAG repeat expansion, leading to an expanded polyglutamine stretch in the resulting type-specific protein. To comparatively investigate determinants of disease progression, we analyzed demographic and genetic data and three-year clinical time courses of neurological symptoms. The aim was to provide tailored marker candidates and prediction models to support type-specific clinical monitoring and trial design.MethodsTo analyze relationships among the different neurological symptoms, we examined co-occurrence patterns of deterioration events. Predicting disease progression was treated as a survival analysis problem.ResultsThe data set contained 1538 subjects from five different longitudinal cohorts and 3802 visits. The pattern of neurological symptoms that showed progression varied with the SCA type. Mining of the progression data revealed the Scale for the Assessment and Rating of Ataxia (SARA) sum score to be the most representative descriptor of disease progression, reflecting progression of the majority of the other included symptoms. We trained models for predicting the progression of each neurological symptom for each SCA type from genetic features, age and symptoms at the baseline visit. The most universal predictors included the SARA sum score, gait and the CAG repeat length of the expanded allele. Finally, deterioration in disease staging was studied in detail: For the milestones of deterioration, (i) the need to use walking aids and (ii) the requirement to use a wheelchair, we discovered common as well as diverging predictive markers. For clinical interpretability, a decision tree was built to indicate the probability of progression within 3 years in dependence of the top predictive features.DiscussionData-driven approaches are potent tools to identify the main contributing features of progression prediction. Progression events for the disease stage were predictable from the baseline neurological status. Remarkably, a limited number of features had predictive importance, and only few were shared among all four SCA types, including gait and the SARA sum score, confirming the need for type-specific models.
Preventing CpG island hypermethylation in oocytes safeguards mouse development
Authors: Kawamura Yumiko K. , Ozonov Evgeniy A. , Papasaikas Panagiotis , Kondo Takashi , Nguyen Nhuong V. , Stadler Michael B. , Smallwood Sebastien A. , Koseki Haruhiko , Peters Antoine H.F.M 
Published: May 2024

SUMMARYIn mammalian somatic and male germline cells, genomes are extensively DNA methylated (DNAme). In oocytes, however, DNAme is largely limited to transcribed regions only. Regulatory CpG-island (CGI) sequences are also devoid of repressive DNAme in somatic and germ cells of both sexes. The mechanisms restrictingde novoDNAme acquisition in developing oocytes, at CGIs and globally, and the relevance thereof for regulating zygotic gene expression and embryo development after fertilization are largely unknown. Here we show that the histone H3 lysine 36 dimethyl (H3K36me2) demethylases KDM2A and KDM2B prevent genome-wide accumulation of H3K36me2, thereby impeding global DNMT3A-catalyzedde novoDNAme, including at CGI gene promoters. By recruiting variant Polycomb Repressive Complex 1 (vPRC1), they further control H2A mono-ubiquitin deposition and vPRC1-dependent gene repression. Through genetic perturbations, we demonstrate that aberrantDnmt3a-dependent DNAme established inKdm2a/Kdm2bdouble mutant oocytes represses transcription from maternal loci in two-cell embryos. The lethality ofKdm2a/Kdm2bmaternally deficient pre-implantation embryos is suppressed byDnmt3adeficiency during oogenesis. Hence, KDM2A/KDM2B are essential for confining the oocyte DNA methylome, conferring competence for early embryonic development. Our research implies that the reprogramming capacity eminent to early embryos is insufficient to erase aberrant DNAme from maternal chromatin, and that early development is vulnerable to gene dosage haplo-insufficiency effects.HIGHLIGHTSDemethylation of H3K36me2 by KDM2A and KDM2B prevents aberrant de novo DNA methylation in mouse oocytes.Sequence composition and H3K4me3 modulate the probability for aberrant H3K36me2 and DNA methylation at CpG islands.Aberrant oocyte DNA methylation is not reprogrammed in early embryos and suppresses maternal gene transcription.Aberrant oocyte DNA methylation causes embryonic lethality during pre-implantation development.GRAPHICAL SUMMARY
Real-time optimization to enhance noninvasive cortical excitability assessment in the human dorsolateral prefrontal cortex
Authors: Parmigiani Sara , Cline Christopher C. , Sarkar Manjima , Forman Lily , Truong Jade , Ross Jessica M. , Gogulski Juha , Keller Corey J. 
Published: May 2024

ABSTRACTObjectiveWe currently lack a robust noninvasive method to measure prefrontal excitability in humans. Concurrent TMS and EEG in the prefrontal cortex is usually confounded by artifacts. Here we asked if real-time optimization could reduce artifacts and enhance a TMS-EEG measure of left prefrontal excitability.MethodsThis closed-loop optimization procedure adjusts left dlPFC TMS coil location, angle, and intensity in real-time based on the EEG response to TMS. Our outcome measure was the left prefrontal early (20-60 ms) and local TMS-evoked potential (EL-TEP).ResultsIn 18 healthy participants, this optimization of coil angle and brain target significantly reduced artifacts by 63% and, when combined with an increase in intensity, increased EL-TEP magnitude by 75% compared to a non-optimized approach.ConclusionsReal-time optimization of TMS parameters during dlPFC stimulation can enhance the EL-TEP.SignificanceEnhancing our ability to measure prefrontal excitability is important for monitoring pathological states and treatment response.HighlightsWe developed a real-time closed-loop optimization procedure to obtain high amplitude early local TEPs (EL-TEPs) from dlPFC TMS.Sequential optimization of coil angle and brain target reduced artifacts by 63%.Sequential optimization of coil angle, brain target, and intensity increased EL-TEP amplitude by 75%.