bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of N-163 strain ofAureobasidium pullulans-produced beta-glucan in improving muscle strength and function in patients with Duchenne muscular dystrophy; Results of a 6-month non-randomised open-label linear clinical trial
Authors: Raghavan Kadalraja , Sivakumar Thanasekar , Bharatidasan Sudhakar S , Srinivasan Subramaniam , Dedeepiya Vidyasagar Devaprasad , Ikewaki Nobunao , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK 
Published: May 2023

AbstractDuchenne muscular dystrophy (DMD) is a debilitating genetic disease that causes gradual muscle weakening and early mortality. After a 45-day clinical pilot study and a pre-clinical study in mdx mice demonstrating safety and efficacy, and anti-fibrotic and anti-inflammatory effects, respectively, of anAureobasidium pullulansN-163 strain-produced B-1,3–1,6-glucan. We conducted this linear six-month clinical study to assess its efficacy. Twelve ambulatory and 12 non-ambulatory individuals with DMD were included; all received the N-163 strain of A.pullulans produed beta-glucan dietary supplement orally in addition to the standard treatment regimen, which included steroids. The Medical Research Council muscle score improved in 11 patients in the ambulatory group and in 8 patients in the non-ambulatory group. The six-minute walk test distance improved in nine patients, with a 29.5-meter average improvement. The North Star Ambulatory Assessment improved by 1 unit in three patients. This safe beta-glucan food supplement improved muscle function within 6 months. A comprehensive, multi-centric clinical research should be conducted for unravelling its potential as a disease-modifying drug adjuvant in DMD.
Improving Multichannel Raw Electroencephalography-based Diagnosis of Major Depressive Disorder via Transfer Learning with Single Channel Sleep Stage Data*
Authors: Ellis Charles A. , Sattiraju Abhinav , Miller Robyn L. , Calhoun Vince D. 
Published: May 2023

AbstractAs the field of deep learning has grown in recent years, its application to the domain of raw resting-state electroencephalography (EEG) has also increased. Relative to traditional machine learning methods or deep learning methods applied to manually engineered features, there are fewer methods for developing deep learning models on small raw EEG datasets. One potential approach for enhancing deep learning performance, in this case, is the use of transfer learning. While a number of studies have presented transfer learning approaches for manually engineered EEG features, relatively few approaches have been developed for raw resting-state EEG. In this study, we propose a novel EEG transfer learning approach wherein we first train a model on a large publicly available single-channel sleep stage classification dataset. We then use the learned representations to develop a classifier for automated major depressive disorder diagnosis with raw multichannel EEG. Statistical testing reveals that our approach significantly improves the performance of our model (p < 0.05), and we also find that the performance of our approach exceeds that of many previous studies using both engineered features and raw EEG. We further examine how transfer learning affected the representations learned by the model through a pair of explainability analyses, identifying key frequency bands and channels utilized across models. Our proposed approach represents a significant step forward for the domain of raw resting-state EEG classification and has broader implications for use with other electrophysiology and time-series modalities. Importantly, it has the potential to expand the use of deep learning methods across a greater variety of raw EEG datasets and lead to the development of more reliable EEG classifiers.
Blood protein levels predict leading incident diseases and mortality in UK Biobank
Authors: Gadd Danni A. , Hillary Robert F. , Kuncheva Zhana , Mangelis Tasos , Cheng Yipeng , Dissanayake Manju , Admanit Romi , Gagnon Jake , Lin Tinchi , Ferber Kyle , Runz Heiko ,   Biogen Biobank Team, Marioni Riccardo E. , Foley Christopher N. , Sun Benjamin B. 
Published: May 2023

AbstractThe circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality, over 16 years of electronic health linkage in the UK Biobank (N=47,600). We report 3,201 associations between 961 protein levels and 21 incident outcomes, identifying proteomic indicators of multiple morbidities. Next, protein-based scores (ProteinScores) are developed using penalised Cox regression. When applied to test sets, six ProteinScores improve Area Under the Curve (AUC) estimates for the 10-year onset of incident outcomes beyond age, sex and a comprehensive set of 24 lifestyle factors, clinically-relevant biomarkers and physical measures. Furthermore, the ProteinScore for type 2 diabetes outperformed a polygenic risk score, a metabolomic score and HbA1c – a clinical marker used to monitor and diagnose type 2 diabetes. These data characterise early proteomic contributions to major age-related disease and demonstrate the value of the plasma proteome for risk stratification.
Spatial analysis of methicillin-resistantStaphylococcus aureuscarriage (MRSA) at hospital admission in a livestock dense region
Authors: Arntzen Vera H. , Feenstra Sabiena G. , Benincà Elisa , Le T.T.N. , Mascini Ellen M. , Nabuurs-Franssen Marrigje H. , Voss Andreas , Marik Agi M. , de Jong Eefje , Silvis Welmoed , Schijffelen Maarten J. , Schneeberger Peter , Hopman Joost , Korthals Altes Hester , Wertheim Heiman F.L. 
Published: May 2023

SummaryTitleSpatial analysis of methicillin-resistantStaphylococcus aureuscarriage (MRSA) screening yield at hospital admission in a livestock-dense regionPurposeIn the Netherlands, patients with a risk factor for methicillin-resistantStaphylococcus aureus(MRSA) carriage, such as foreign hospital stay and contact with livestock (pigs, veal calves and/or broilers) are actively screened upon hospital admission. This study aimed to give insight in the geographical clustering patterns of MRSA carriage among these patients in a livestock-dense region.MethodsA retrospective study was performed using medical records and laboratory results of MRSA screened patients admitted to seven hospitals in the provinces of Gelderland and Noord-Brabant, covering the period from 01/2011 to 02/2017. SaTScan spatial scanning identified cluster areas with an increased MRSA carriage risk in postal codes compared to the surrounding areas.Results15 546 patients were included, among which 10.0% (n=1499) were MRSA carriers. Four significant, typically highly pig-dense MRSA carriage hotspots were identified, where the relative risk of carriage ranged from 2.1 to 3.4 compared to the surrounding area.ConclusionMRSA carriage risk clustered in certain areas, suggesting an association between livestock density (mainly pigs) and the MRSA carriage risk for the screened population at hospital admission. It needs to be explored when proximity (not contact) to livestock should be considered a risk factor. Considering analytical difficulties we encountered it is recommended to harmonize culture methods and data acquisition across hospitals to facilitate analysis for improving MRSA screening policy.ImpactsThe fraction MRSA carriers among patients with livestock contact notified in the hospital system in this study was 22.7%, showing the effectiveness of the Search and Destroy policy.MRSA carriage in the Dutch Province Gelderland is clustered in certain hotspots, located in pig-dense areas.Culture methods and data acquisition should be harmonized across hospitals to facilitate analysis for improving MRSA screening policy.
Hear my Voice: Understanding how community health workers in the Peruvian Amazon expanded their roles to mitigate the impact of the COVID-19 pandemic through Community-Based Participatory Action Research
Authors: Samsamshariat Tina , Madhivanan Purnima , Reyes Alexandra , Moya Eva M. , Meza-Sánchez Graciela , Reinders Stefan , Blas Magaly M. 
Published: May 2023

AbstractIntroductionThe COVID-19 pandemic led to the collapse of the Peruvian health system, which disrupted healthcare access for indigenous communities in the Amazon. We aimed to understand how the COVID-19 pandemic transformed the responsibilities of community health workers (CHWs) from indigenous communities in the Peruvian Amazon so policymakers can support indigenous health efforts.MethodsFourteen CHWs from Loreto, Peru participated in a community-based Participatory Action Research (CBPR) project using Photovoice, a technique that encourages vulnerable groups to take photos and develop stories illustrating their lived experiences. Participants were recruited fromMamás del Río, a local university-based program, through purposive sampling. CHWs were trained in Photovoice and asked to photograph how the pandemic affected their lives and work. Participants met four times over five months to share photos and develop action items. Data were organized into key themes using a general inductive method. Final photos and action items were shared with policymakers during galleries in Iquitos and Lima.ResultsCHWs took a total of 36 photos with 33 accompanying texts highlighting their roles during the pandemic. Four core themes emerged: (1) the collapse of social infrastructure, (2) the use of medicinal plants versus pharmaceuticals, (3) the community adaptations and struggles, and (4) the importance of CHWs. CHWs expanded their responsibilities or leveraged their leadership across these themes to support COVID-19 patients, vaccination, and mandates without training or resources from the government. CHWs asked policymakers for formal integration into the health system, standardization of CHW training, and better management of community pharmacies.ConclusionCHWs, who work on a voluntary basis, took on additional roles during the pandemic with little to no training from the government. CHWs demonstrated how their roles could be better supported by the government to ameliorate future health catastrophes in the Peruvian Amazon.Short SummaryHealth care delivery in the Peruvian Amazon collapsed during the COVID-19 pandemic. Community health workers provided frontline care, education, and logistical support without formal training, resources, or compensation from the Ministry of Health. The government can better leverage, supervise, recognize, and integrate the role of community health workers to strengthen the health system.
Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID with Exercise Capacity and Chronotropic Incompetence among People with HIV
Authors: Durstenfeld Matthew S. , Peluso Michael J. , Spinelli Matthew A. , Li Danny , Hoh Rebecca , Gandhi Monica , Henrich Timothy J. , Aras Mandar A. , Long Carlin S. , Deeks Steven G. , Hsue Priscilla Y. 
Published: May 2023

ABSTRACTBackgroundLong COVID has been associated with reduced exercise capacity, but whether SARS-CoV-2 infection or Long COVID is associated with reduced exercise capacity among people with HIV (PWH) has not been reported. We hypothesized that PWH with cardiopulmonary post-acute symptoms of COVID-19 (PASC) would have reduced exercise capacity due to chronotropic incompetence.MethodsWe conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH. We evaluated associations of HIV, prior SARS-CoV-2 infection, and cardiopulmonary PASC with exercise capacity (peak oxygen consumption, VO2) and adjusted heart rate reserve (AHRR, chronotropic measure) with adjustment for age, sex, and body mass index.ResultsWe included 83 participants (median age 54, 35% female). All 37 PWH were virally suppressed; 23 (62%) had prior SARS-CoV-2 infection, and 11 (30%) had PASC. Peak VO2was reduced among PWH (80% predicted vs 99%; p=0.005), a difference of 5.5 ml/kg/min (95%CI 2.7-8.2, p<0.001). Chronotropic incompetence more prevalent among PWH (38% vs 11%; p=0.002), and AHRR was reduced among PWH (60% vs 83%, p<0.0001). Among PWH, exercise capacity did not vary by SARS-CoV-2 coinfection, but chronotropic incompetence was more common among PWH with PASC: 3/14 (21%) without SARS-CoV-2, 4/12 (25%) with SARS-CoV-2 without PASC, and 7/11 (64%) with PASC (p=0.04 PASC vs no PASC).ConclusionsExercise capacity and chronotropy are lower among PWH compared to SARS-CoV-2 infected individuals without HIV. Among PWH, SARS-CoV-2 infection and PASC were not strongly associated with reduced exercise capacity. Chronotropic incompetence may be a mechanism limiting exercise capacity among PWH.
Open science practices in research published in surgical journals: A cross-sectional study
Authors: Pathak Kavya , Marwaha Jayson S. , Chen Hao Wei , Krumholz Harlan M. , Matthews Jeffrey B. 
Published: May 2023

AbstractOpen science practices are research tools used to improve research quality and transparency. These practices have been used by researchers in various medical fields, though the usage of these practices in the surgical research ecosystem has not been quantified. In this work, we studied the use of open science practices in general surgery journals. Eight of the highest-ranked general surgery journals by SJR2 were chosen and their author guidelines were reviewed. From each journal, 30 articles published between January 1, 2019 and August 11, 2021 were randomly chosen and analyzed. Five open science practices were measured (preprint publication prior to peer-reviewed publication, use of Equator guidelines, study protocol preregistration prior to peer-reviewed publication, published peer review, and public accessibility of data, methods, and/or code). Across all 240 articles, 82 (34%) used one or more open science practices. Articles in theInternational Journal of Surgeryshowed greatest use of open science practices, with a mean of 1.6 open science practices compared to 0.36 across the other journals (p<.001). Adoption of open science practices in surgical research remains low, and further work is needed to increase utilization of these tools.
A multi-ancestry genome-wide meta-analysis, fine-mapping, and gene prioritization approach to characterize the genetic architecture of adiponectin
Authors: Sarsani Vishal , Brotman Sarah M. , Xianyong Yin , Silva Lillian Fernandes , Laakso Markku , Spracklen Cassandra N. 
Published: May 2023

AbstractPrevious genome-wide association studies (GWAS) for adiponectin, a complex trait linked to type 2 diabetes and obesity, identified >20 associated loci. However, most loci were identified in populations of European ancestry, and many of the target genes underlying the associations remain unknown. We conducted a multi-ancestry adiponectin GWAS meta-analysis in ≤46,434 individuals from the METSIM cohort and the ADIPOGen and AGEN consortiums. We combined study-specific association summary statistics using a fixed-effects, inverse variance-weighted approach. We identified 22 loci associated with adiponectin (P< 5×10−8), including 15 known and 7 previously unreported loci. Among individuals of European ancestry, GCTA-COJO identified 14 additional distinct signals at theADIPOQ,CDH13,HCAR1, andZNF664loci. Leveraging the multi-ancestry data, FINEMAP + SuSiE identified 46 causal variants (PP>0.9), which also exhibited potential pleiotropy for cardiometabolic traits. To prioritize target genes at associated loci, we propose a combinatorial likelihood scoring formalism (“GPScore”) based on measures derived from 11 gene prioritization strategies and the physical distance to the transcription start site. With “GPScore”, we prioritize the 30 most probable target genes underlying the adiponectin-associated variants in the multi-ancestry analysis, including well-known causal genes (e.g.,ADIPOQ,CDH13) and novel genes (e.g.,CSF1,RGS17). Functional association networks revealed complex interactions of prioritized genes, their functionally connected genes, and their underlying pathways centered around insulin and adiponectin signaling, indicating an essential role in regulating energy balance in the body, inflammation, coagulation, fibrinolysis, insulin resistance, and diabetes. Overall, our analyses identify and characterize adiponectin association signals and inform experimental interrogation of target genes for adiponectin.
Genomic variation associated with cardiovascular disease progression following preeclampsia: A systematic review
Authors: Krishnamurthy Gayathry , Nguyen Phuong Tram , Tran Bao Ngoc , Phan Hoang T , Brennecke Shaun P. , Moses Eric K , Melton Phillip E. 
Published: May 2023

ABSTRACTBackgroundWomen with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE.MethodsA literature search of primary sources through PubMed, Scopus, Web of Science and Embase via OVID was performed. Studies published from January 1st, 1980, to February 02nd, 2023, that investigated genomics in PE and CVD were eligible for inclusion. Studies that did not include CVD or related risk factors as outcome, were in non-human species or focused on pregnancy complications other than PE were excluded. Included studies were screened based on Cochrane systematic review guidelines in conjunction with the PRISMA 2020 checklist. Eligible articles were further assessed for quality using the Newcastle-Ottawa scale.ResultsA total of 8929 articles were screened with 14 studies subjected to quality assessment. Following further evaluation, six studies were included for final review. All six of these studies were heterogenous in regard to CVD/risk factor as outcome, gene mapping approach, and in different targeted genes. The only common variable across all six studies was use of a case-control study design.ConclusionsOur results provide critical insight into the heterogeneous nature of genomic studies investigating CVD following PE and highlight the urgent need for longitudinal studies to further investigate the genetic variation underlying the progression to CVD following PE.
A global catalog of whole-genome diversity from 233 primate species
Authors: Kuderna Lukas F.K. , Gao Hong , Janiak Mareike C. , Kuhlwilm Martin , Orkin Joseph D. , Bataillon Thomas , Manu Shivakumara , Valenzuela Alejandro , Bergman Juraj , Rouselle Marjolaine , Silva Felipe Ennes , Agueda Lidia , Blanc Julie , Gut Marta , de Vries Dorien , Goodhead Ian , Harris R. Alan , Raveendran Muthuswamy , Jensen Axel , Chuma Idriss S. , Horvath Julie , Hvilsom Christina , Juan David , Frandsen Peter , Schraiber Joshua G. , de Melo Fabiano R. , Bertuol Fabricio , Byrne Hazel , Sampaio Iracilda , Farias Izeni , Amaral João Valsecchi do , Messias Malu , da Silva Maria N. F. , Trivedi Mihir , Rossi Rogerio , Hrbek Tomas , Andriaholinirina Nicole , Rabarivola Clément J. , Zaramody Alphonse , Jolly Clifford J. , Phillips-Conroy Jane , Wilkerson Gregory , Abee Christian , Simmons Joe H. , Fernandez-Duque Eduardo , Kanthaswamy Sree , Shiferaw Fekadu , Wu Dongdong , Zhou Long , Shao Yong , Zhang Guojie , Keyyu Julius D. , Knauf Sascha , Le Minh D. , Lizano Esther , Merker Stefan , Navarro Arcadi , Nadler Tilo , Khor Chiea Chuen , Lee Jessica , Tan Patrick , Lim Weng Khong , Kitchener Andrew C. , Zinner Dietmar , Gut Ivo , Melin Amanda , Guschanski Katerina , Schierup Mikkel Heide , Beck Robin M. D. , Umapathy Govindhaswamy , Roos Christian , Boubli Jean P. , Rogers Jeffrey , Farh Kyle , Bonet Tomas Marques 
Published: May 2023

AbstractThe rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology, and is urgent given severe threats these species are facing. Here, we present high coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human-specific. This study will open a wide range of research avenues for future primate genomic research.One-Sentence SummaryThe whole genome sequences of 233 primate species provide insight into the determinants of genetic diversity, phylogenomics, and human uniqueness.
Stealth liposomes encapsulating a potent ACAT1/SOAT1 inhibitor F12511: pharmacokinetic, biodistribution and toxicity studies in wild-type mice, and efficacy studies in triple transgenic Alzheimer Disease mice
Authors: Torre Adrianna L. De La , Huynh Thao N. , Chang Catherine C.Y. , Pooler Darcy B. , Ness Dylan , Lewis Lionel , Pannem Sanjana , Feng Yichen , Samkoe Kimberley S. , Hickey William F. , Chang Ta Yuan 
Published: May 2023

AbstractCholesterol is essential to cellular function and is stored as cholesteryl esters (CEs). CEs biosynthesis is responsible by the enzymes acyl-CoA: cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), with ACAT1 as the primary isoenzyme in most cells in humans. ACATs are targets for atherosclerosis therapies and may also be promising targets for treating Alzheimer’s Disease (AD). F12511 is a high-affinity ACAT1 inhibitor that has passed phase 1 safety tests for anti-atherosclerosis. Previously, we had developed a nanoparticle system to encapsulate a large concentration of F12511 into a stealth liposome (DSPE-PEG2000with egg phosphatidylcholine). Here, we injected the nanoparticle encapsulated F12511 (nanoparticle F) intravenously (IV) to wild-type (WT) mice and performed HPLC/MS/MS analysis and ACAT enzyme activity measurement. The results demonstrated that F12511 was present within the mouse brain after a single IV but did not over-accumulate in the brain or other tissues after repeated IVs. Histological examination showed that F12511 did not cause overt neurological or systemic toxicity. We then showed that 2-week IV delivery of nanoparticle F to aging 3xTg AD mice ameliorated amyloidopathy, reduced hyperphosphorylated tau and non-phosphorylated tau, and reduced neuroinflammation. This work lays the foundation with nanoparticle F as a possible therapy for AD and other neurodegenerative diseases.