bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Quality and Adequacy of Pan Retinal Photocoagulation in Proliferative Diabetic Retinopathy using Ultra-wide Field Imaging
Authors: L Sowmya , Banerjee Mousumi , Venkatesh Pradeep , Azad Shorya Vardhan , Joshi Hemant Kumar , Chawla Rohan , Kumar Vinod , Vohra Rajpal , Kumar Atul 
Published: July 2023

Abstract

Purpose:
To assess the characteristics of completed PRP, using UWF in PDR.

Methods:
Quantitative assessment of UWF images of 133 patients with PDR with completed PRP was made using Image J software. The parameters assessed included distance of laser spots from the optic disc, foveal centre, superior and inferior arcade, extent of maximum width of laser. Areas assessed were total area of the image, area of the inner limit within which laser spots are restricted, minimum areas of unlasered patches, total area lasered, and ideal area to be covered by PRP.

Results:
201 images were assessed for final analysis. The mean distance of laser spots from the optic disc (nasal) was 4.2 mm ± 2.4 mm, and from the foveal centre (temporal) was 6.6 mm ± 2.5 mm. The mean distance of laser spots from the superior arcade vessel was 3.2mm ± 1.9 mm, and 6.2mm ± 4.4 mm from the inferior arcade. The mean area of the retina that should have been ideally lasered was found to be 900 mm2 ± 267 mm2, actual area lasered was found to be 681 mm2 ± 254.4 mm2 .

Conclusion:
About a quarter area of the retina continues to remain ischemic by the lack of inadequate coverage of PRP. Further longitudinal studies are recommended, using UWFI to objectively assess the adequacy of PRP and its role in modulating the course of progression of the retinopathy.
Dissemination and Evaluation of an Opioid Hazard Awareness Training for Stone, Sand, and Gravel Miners
Authors: Roelofs Cora , Hansen Julia 
Published: July 2023

Objective
In response to elevated risk factors, an opioid hazard awareness training for the sand, stone, and gravel mining sector was developed and embedded in annual safety training.

Methods
After positive results from a prior study among Massachusetts workers, a revised training was disseminated across the United States. Two hundred post-training surveys were obtained and compared with results from the Massachusetts cohort.

Results
Participants’ knowledge about opioid-based medications, confidence in talking to a doctor about opioids and/or to a coworker about their own use of opioids, and ability to refer struggling coworkers to resources improved. Massachusetts respondents had slightly more favorable responses. Both cohorts had strong positive views of the training.

Conclusions
These results highlight the feasibility and effectiveness of opioid hazard prevention training for a high-risk worker population.
Thrombotic Features as the Primary Cause of SARS-CoV-2 Related Acute Abdomen in Children
Authors: Amoroso Angela , Di Stasio Fabiana , Ranucci Giusy , Betalli Pietro , Cheli Maurizio , Dalla Rosa Davide , D’Anna Carolina , Gaglione Giovanni , Giannotti Giulia , Licini Lisa , Mandato Claudia , Massazza Gabriella , Orlando Francesca , Morotti Denise , Rocco Michele , Sonzogni Aurelio , Tipo Vincenzo , Verdoni Lucio , D’Antiga Lorenzo , Norsa Lorenzo 
Published: July 2023

Objectives:
We performed a retrospective case control study to evaluate the histological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive pediatric patients undergoing laparoscopic exploration for acute abdomen symptoms. To our knowledge this is the first study that analyzes histopathological characteristics of abdominal tissues in SARS-CoV-2 children.

Study design:
We enrolled 8 multisystem inflammatory syndrome in children (MIS-C) patients and 4 SARS-CoV-2 positive patients who underwent intestinal resection versus 36 control appendectomies from 2 pediatric tertiary referral centers between March 2020 and July 2021. Surgical resection samples were evaluated on several histological sections focusing on general inflammatory pattern and degree of inflammation. Peculiar histological features (endotheliitis and vascular thrombosis) were semi-quantitatively scored respectively in capillary, veins, and arteries.

Results:
All SARS-CoV-2 related surgical samples showed thrombotic patterns. Those patterns were significantly less frequent in SARS-CoV-2 negative appendectomies (P = 0.004). The semi-quantitative score of thrombosis was significantly higher (P = 0.002) in patients with SARS-CoV-2 related procedures.

Conclusions:
Our results showed that SARS-CoV-2 can cause thrombotic damage in abdominal tissues both in the acute phase of the infection (SARS-CoV-2 related appendectomies) and secondary to cytokine storm (MIS-C).
Impact of the COVID-19 Pandemic on a Clinical Trial: A Quantitative Report on Study Engagement and Strategies
Authors: Brown Shaaron E. , Miller Meagan , Darring Jodi , Inamdar Ketaki , Salgaonkar Arya , Burnsed Jennifer C. , Stevenson Richard D. , Shall Mary S. , Harper Amy D. , Hendricks-Munoz Karen D. , Thacker Leroy R. , Hyde Meg , Dusing Stacey C. 
Published: July 2023

Introduction:
The COVID-19 pandemic impacted clinical research worldwide potentially altering research findings. The study purpose was to measure the effect of the pandemic on recruitment, retention, assessment, and intervention completion rates.

Methods:
Enrollment and participation data from a clinical trial evaluating efficacy of a physical therapy intervention for high-risk preterm infants were compared across 3 pandemic periods (February 2019 through November 2021).

Results:
Recruitment, retention, assessment, and intervention completion rates were lowest during the peak pandemic period.

Conclusions:
In compliance with the Human Subjects Review Board, and for the participants' and staff safety, transition from in-person to telehealth or hybrid visits was required to continue this longitudinal study. Despite the negative effect of the pandemic, parental resilience and commitment to the study was clear. Flexibility, quick action, dedication, and efficiency of the research team were key elements enabling study continuation with successful transition to telehealth assessments/interventions during the peak pandemic period.
The value of chest radiography after chest tube removal in nonventilated trauma patients: A post hoc analysis of a multicenter prospective cohort study
Authors: Sweet Arthur A.R. , Kobes Tim , Houwert Roderick M. , Leenen Luke P.H. , de Jong Pim A. , Veldhuis Wouter B. , IJpma Frank F.A. , van Baal Mark C.P.M. 
Published: July 2023

BACKGROUND
Chest tubes are commonly placed in trauma care to treat life-threatening intrathoracic injuries by evacuating blood or air from the pleural cavity. Currently, it is common practice to routinely obtain chest radiographs between 1 to 8 hours after chest tube removal, while the necessity of it has been questioned. This study describes the “ins-and-outs” of chest tubes and evaluates the value of routine postremoval chest radiography in nonventilated trauma patients.

METHODS
A post hoc analysis of a multicenter observational prospective cohort study was performed in blunt chest trauma patients admitted with multiple rib fractures to two level 1 trauma centers between January 2018 and March 2021 and treated with one or more chest tubes. Exclusion criteria were mechanical ventilation during chest tube removal, missing reports of postremoval chest radiography, transfer to another hospital, or mortality before chest tube removal. Descriptive analyses were performed to calculate the number of findings on postremoval chest radiographs and reinterventions.

RESULTS
A total of 207 patients were included for analysis of whom 14 underwent bilateral chest tube placement, resulting in 221 chest tube removals investigated in this study. The mean ± SD age was 58 ± 17 years, 71% were male, 73% had American Society of Anesthesiologists scores of 1 or 2, and the median Injury Severity Score was 19 (interquartile range, 14–29). In 68 of 221 chest tube removals (31%), postremoval chest radiography showed increased or recurrent intrathoracic pathology (i.e., 13% pneumothorax, 18% pleural fluid, and 8% atelectasis). Only two (3%) of these patients underwent a same-day reintervention based on these findings, of whom one had signs or symptoms of recurrent pathology and one was asymptomatic.

CONCLUSION
It seems safe to omit routine use of postremoval chest radiography in nonventilated blunt chest trauma patients and to selectively use imaging in those patients presenting with clinical signs or symptoms after chest tube removal.

LEVEL OF EVIDENCE
Diagnostic Tests/Criteria; Level IV.
On automated model discovery and a universal material subroutine
Authors: Peirlinck Mathias , Linka Kevin , Hurtado Juan A. , Kuhl Ellen 
Published: July 2023

AbstractConstitutive modeling is the cornerstone of computational and structural mechanics. In a finite element analysis, the constitutive model is encoded in the material subroutine, a function that maps local strains onto stresses. This function is called within every finite element, at each integration point, within every time step, at each Newton iteration. Today’s finite element packages offer large libraries of material subroutines to choose from. However, the scientific criteria for model selection remain highly subjective and prone to user bias. Here we fully automate the process of model selection, autonomously discover the best model and parameters from experimental data, encode all possible discoverable models into a single material subroutine, and seamlessly integrate this universal material subroutine into a finite element analysis. We prototype this strategy for tension, compression, and shear data from human brain tissue and perform a hyperelastic model discovery from twelve possible terms. These terms feature the first and second invariants, raised to the first and second powers, embedded in the identity, exponential, and logarithmic functions, generating 22×2×3= 4096 models in total. We demonstrate how to integrate these models into a single universal material subroutine that features the classical neo Hooke, Blatz Ko, Mooney Rivlin, Demiray, Gent, and Holzapfel models as special cases. Finite element simulations with our universal material subroutine show that it specializes well to these widely used models, generalizes well to newly discovered models, and agrees excellently with both experimental data and previous simulations. It also performs well within realistic finite element simulations and accurately predicts stress concentrations in the human brain for six different head impact scenarios. We anticipate that integrating automated model discovery into a universal material subroutine will generalize naturally to more complex anisotropic, compressible, and inelastic materials and to other nonlinear finite element platforms. Replacing dozens of individual material subroutines by a single universal material subroutine that is populated directly via automated model discovery—entirely without human interaction—makes finite element analyses more accessible, more robust, and less vulnerable to human error. This could forever change how we simulate materials and structures.
Deciphering the genetic architecture of atrial fibrillation offers insights into disease prediction, pathophysiology and downstream sequelae
Authors: Yuan Shuai , Li Yuying , Wang Lijuan , Xu Fengzhe , Chen Jie , Levin Michael G , Xiong Ying , Voight Benjamin F. , Damrauer Scott M , Gill Dipender , Burgess Stephen , Åkesson Agneta , Michaëlsson Karl , Li Xue , Shen Xia , Larsson Susanna C. 
Published: July 2023

AbstractAimsThe study aimed to discover novel genetic loci for atrial fibrillation (AF), explore the shared genetic etiologies between AF and other cardiovascular and cardiometabolic traits, and uncover AF pathogenesis using Mendelian randomization analysis.Methods and resultsWe conducted a genome-wide association study meta-analysis including 109,787 AF cases and 1,165,920 controls of European ancestry and identified 215 loci, among which 91 were novel. We performed Genomic Structural Equation Modeling analysis between AF and four cardiovascular comorbidities (coronary artery disease, ischemic stroke, heart failure, and vneous thromboembolism) and found 189 loci shared across these diseases as well as a universal genetic locus shared by atherosclerotic outcomes (i.e., rs1537373 nearCDKN2B). Three genetic loci (rs10740129 nearJMJD1C, rs2370982 nearNRXN3, and rs9931494 nearFTO) were associated with AF and cardiometabolic traits. A polygenic risk score derived from this genome-wide meta-analysis was associated with AF risk (odds ratio 2.36, 95% confidence interval 2.31-2.41 per standard deviation increase) in the UK biobank. This score, combined with age, sex, and basic clinical features, predicted AF risk (AUC 0.784, 95% CI 0.781-0.787) in Europeans. Phenome-wide association analysis of the polygenic risk score identified many AF-related comorbidities of the circulatory, endocrine, and respiratory systems. Phenome-wide and multi-omic Mendelian randomization analyses identified associations of blood lipids and pressure, diabetes, insomnia, obesity, short sleep, and smoking, 27 blood proteins, one gut microbe (genus.Catenibacterium), and 11 blood metabolites with risk to AF.ConclusionsThis genome-wide association study and trans-omic Mendelian randomization analysis provides insights into disease risk prediction, pathophysiology and downstream sequelae.
Robust use of phenotypic heterogeneity at drug target genes for mechanistic insights: application ofcis-multivariable Mendelian randomization toGLP1Rgene region
Authors: Patel Ashish , Gill Dipender , Shungin Dmitry , Mantzoros Christos S. , Knudsen Lotte Bjerre , Bowden Jack , Burgess Stephen 
Published: July 2023

AbstractPhenotypic heterogeneity at genomic loci encoding drug targets can be exploited by multivariable Mendelian randomization to provide insight on the pathways by which pharmacological interventions may affect disease risk. However, statistical inference in such investigations may be poor if overdispersion heterogeneity in measured genetic associations is unaccounted for. In this work, we first develop conditional F-statistics for dimension-reduced genetic associations that enable more accurate measurement of phenotypic heterogeneity. We then develop a novel extension for two-sample multivariable Mendelian randomization that accounts for overdispersion heterogeneity in dimension-reduced genetic associations. Our empirical focus is to use genetic variants in theGLP1Rgene region to understand the mechanism by which GLP1R agonism affects coronary artery disease (CAD) risk. Colocalization analyses indicate that distinct variants in theGLP1Rgene region are associated with body mass index and type 2 diabetes. Multivariable Mendelian randomization analyses that were corrected for overdispersion heterogeneity suggest that bodyweight lowering rather than type 2 diabetes liability lowering effects of GLP1R agonism are more likely contributing to reduced CAD risk. Tissue-specific analyses prioritised brain tissue as the most likely to be relevant for CAD risk, of the tissues considered. We hope the multivariable Mendelian randomization approach illustrated here is widely applicable to better understand mechanisms linking drug targets to diseases outcomes, and hence to guide drug development efforts.
APOE4/4 is linked to damaging lipid droplets in Alzheimer’s microglia
Authors: Haney Michael S. , Pálovics Róbert , Munson Christy Nicole , Long Chris , Johansson Patrik , Yip Oscar , Dong Wentao , Rawat Eshaan , West Elizabeth , Schlachetzki Johannes CM , Tsai Andy , Guldner Ian Hunter , Lamichhane Bhawika S. , Smith Amanda , Schaum Nicholas , Calcuttawala Kruti , Shin Andrew , Wang Yung-Hua , Wang Chengzhong , Koutsodendris Nicole , Serrano Geidy E , Beach Thomas G , Reiman Eric M , Glass Christopher K , Abu-Remaileh Monther , Enejder Annika , Huang Yadong , Wyss-Coray Tony 
Published: July 2023

AbstractSeveral genetic risk factors for Alzheimer’s Disease (AD) implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells. However, the relationship between lipid metabolism in glia and AD pathology remains poorly understood. Through single-nucleus RNA-sequencing of AD brain tissue, we have identified a microglial state defined by the expression of the lipid droplet (LD) associated enzymeACSL1with ACSL1-positive microglia most abundant in AD patients with theAPOE4/4genotype. In human iPSC-derived microglia (iMG) fibrillar Aβ (fAβ) inducesACSL1expression, triglyceride synthesis, and LD accumulation in an APOE-dependent manner. Additionally, conditioned media from LD-containing microglia leads to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for AD with microglial LD accumulation and neurotoxic microglial-derived factors, potentially providing novel therapeutic strategies for AD.
Distinguishing cophylogenetic signal from phylogenetic congruence clarifies the interplay between evolutionary history and species interactions
Authors: Perez-Lamarque Benoît , Morlon Hélène 
Published: July 2023

AbstractInterspecific interactions, including host-symbiont associations, can profoundly affect the evolution of the interacting species. Given the phylogenies of host and symbiont clades and knowledge of which host species interact with which symbiont, two questions are often asked: “Do closely related hosts interact with closely related symbionts?” and “Do host and symbiont phylogenies mirror one another?”. These questions are intertwined and can even collapse under specific situations, such that they are often confused one with the other. However, in most situations, a positive answer to the first question, hereafter referred to as “cophylogenetic signal”, does not imply a close match between the host and symbiont phylogenies. It suggests only that past evolutionary history has contributed to shaping present-day interactions, which can arise, for example, through present-day trait matching, or from a single ancient vicariance event that increases the probability that closely related species overlap geographically. A positive answer to the second, referred to as “phylogenetic congruence”, is more restrictive as it suggests a close match between the two phylogenies, which may happen, for example, if symbiont diversification tracks host diversification or if the diversifications of the two clades were subject to the same succession of vicariance events.Here we apply a set of methods (ParaFit, PACo, and eMPRess), which significance is often interpreted as evidence for phylogenetic congruence, to simulations under three biologically realistic scenarios of trait matching, a single ancient vicariance event, and phylogenetic tracking with frequent cospeciation events. The latter is the only scenario that generates phylogenetic congruence, whereas the first two generate a cophylogenetic signal in the absence of phylogenetic congruence. We find that tests of global-fit methods (ParaFit and PACo) are significant under the three scenarios, whereas tests of event-based methods (eMPRess) are only significant under the scenario of phylogenetic tracking. Therefore, significant results from global-fit methods should be interpreted in terms of cophylogenetic signal and not phylogenetic congruence; such significant results can arise under scenarios when hosts and symbionts had independent evolutionary histories. Conversely, significant results from event-based methods suggest a strong form of dependency between hosts and symbionts evolutionary histories. Clarifying the patterns detected by different cophylogenetic methods is key to understanding how interspecific interactions shape and are shaped by evolution.
Extracellular release of a disintegrin and metalloproteinases orchestrates periodontal disease severity
Authors: Aljohmani Ahmad , Heinze Hakon , Gharzia Federico Guillermo , Reda Bashar , Abdrabou Ahmed Mohamed Mostafa , Becker Sören , Bischoff Markus , Hannig Matthias , Yildiz Daniela 
Published: July 2023

AbstractPeriodontal diseases are amongst the most common pathologies worldwide with a high risk for the development of systemic complications. Periodontal disease is driven by oral pathogens such asPorphyromonas gingivalisand the release of inflammatory cytokines. These cytokines (e.g. TNF) or their receptors (IL-1R) are substrates of a disintegrin and metalloproteinases (ADAMs). In a comparative approach, we observed an increase of ADAM8 protein expression and activity in the sulcus fluid of periodontal disease patients correlating with the disease stage. In contrast, the induced ADAM10 expression was decreased.In vitromechanistic studies revealed that bothPorphyromonas gingivalisinfection and the resulting cytokine release orchestrated the release of soluble ADAM8 by keratinocytes and neutrophils as soluble ectodomain and on exosomes, respectively. Furthermore, ADAM8 regulated the release of ADAM10 and MMP9, thereby potentially influencing wound healing and tissue destruction. Thus, the dysregulation of the cell-associated and extracellular ADAM proteolytic activity mainly driven by ADAM8 may be an essential regulatory element in periodontal disease onset and progression. This potential as novel local treatment option should be addressed in future translational studies.
Preferential differential gene expression within the WC1.1+γδ T cell compartment in cattle naturally infected withMycobacterium bovis
Authors: Bhat Sajad A. , Elnaggar Mahmoud , Hall Thomas J. , McHugo Gillian P. , Reid Cian , MacHugh David E. , Meade Kieran G. 
Published: July 2023

ABSTRACTBovine tuberculosis (bTB), caused by infection withMycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterize differential gene expression in γδ T cells – a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known asWorkshop Cluster 1(WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturallyM. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n= 10–12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1-and γδ-) was used to generate transcriptomes using bulk RNA-seq (n= 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in theM. bovis-infected compared to the control groups for the WC1.1+γδ T cell compartment (absolute log2FC ≥ 1.5 and FDRPadj.≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21andEOMES), chemokine receptors (CCR5andCCR7), granzymes (GZMA, GZMM, andGZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, WC1.1+γδ T cells have been proposed as major regulatory cell subset in cattle, and we provide evidence for preferential differential activation of this specific subset in cattle naturally infected withM. bovis.