bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning unmasks the ECG signature of Brugada syndrome
Authors: Melo Luke , Ciconte Giuseppe , Christy Ashton , Vicedomini Gabriele , Anastasia Luigi , Pappone Carlo , Grant Edward 
Published: October 2023

Abstract
One in 10 cases of sudden cardiac death strikes without warning as the result of an inherited arrhythmic cardiomyopathy, such as Brugada Syndrome (BrS). Normal physiological variations often obscure visible signs of this and related life-threatening channelopathies in conventional electrocardiograms (ECGs). Sodium channel blockers can reveal previously hidden diagnostic ECG features, however, their use carries the risk of life-threatening proarrhythmic side effects. The absence of a nonintrusive test places a grossly underestimated fraction of the population at risk of SCD. Here, we present a machine-learning algorithm that extracts, aligns, and classifies ECG waveforms for the presence of BrS. This protocol, which succeeds without the use of a sodium channel blocker (88.4% accuracy, 0.934 AUC in validation), can aid clinicians in identifying the presence of this potentially life-threatening heart disease.
Improved Double-Stranded RNA Extraction and Hyphal Tip-Touch Techniques for the Detection of Mycoviruses
Authors: Mokhtari Samira , Ali Akhtar 
Published: October 2023

Mycoviruses infect a wide range of fungal species, and many of them have double-stranded RNA (dsRNA) genomes. Using a dsRNA technique makes it easier to detect unknown mycoviruses in fungi. Previously, a few studies reported dsRNA extraction methods from fungal tissues, but the procedures required a significant amount of starting material and time, particularly in growing fungal cultures. In this study, we report an efficient and quick dsRNA extraction method that is reproducible to extract quality dsRNA of mycoviruses from a small amount of fungal culture in a short time. Extracted dsRNA was subsequently used in Illumina sequencing and reverse transcription-polymerase chain reaction assays, followed by Sanger sequencing, to confirm the identity of the mycovirus. Additionally, a rapid and efficient technique named hyphal tip-touch (HTT) was developed to identify known mycoviruses without the need for dsRNA extraction. The HTT technique uses the edge of mycelia as a template for preparing complementary DNA in the reverse transcription reaction, which was used in the polymerase chain reaction assay followed by sequencing. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Risk factors for incident venous thromboembolism in patients with renal tumor and inferior vena cava tumor thrombus: A retrospective case-control study
Authors: Wang Hanfeng , Chen Xinran , Wang Kailong , Cao Wenzhe , Huang Qingbo , Peng Cheng , Jia Tongyu , Liang Qiyang , Wang Baojun , Gu Liangyou , Zhang Xu , Ma Xin 
Published: October 2023

Background:
Venous thromboembolism (VTE) is a principal cause of mortality and adverse oncologic outcomes in patients with renal tumor and inferior vena cava tumor thrombus (RT-IVCTT). However, the preoperative thrombotic risk factors in these patients remain not fully characterized.

Objectives:
To identify preoperative thrombotic risk factors in patients with RT-IVCTT.

Patients/Methods:
257 consecutive postsurgical patients with RT-IVCTT aged 18–86 years were enrolled between January 2008 and September 2022. Clinicopathological variables were retrospectively reviewed. A multivariate logistic regression model was performed. Preoperative hemoglobin, neutrophils, and serum albumin levels were analyzed as both continuous and categorical variables.

Results:
VTE was identified in 63 patients (24.5%). On both continuously and categorically coded variables, advanced IVC thrombus (OR 3.2, 95% CI 1.4–7.0; OR 2.7, 95% CI 1.2–6.1), renal sinus fat invasion (OR 3.4, 95% CI 1.6–7.0; OR 3.7, 95% CI 1.8–7.7), IVC wall invasion (OR 3.6, 95% CI 1.6–7.9; OR 4.3, 95% CI 1.9–10.0), IVC blockage status of >75% (OR 5.2, 95% CI 1.7–15.8; OR 6.1, 95% CI 1.9–19.7), and higher neutrophils (OR 1.3, 95% CI 1.0–1.7; OR 2.4, 95% CI 1.1–5.4) were significantly associated with increased VTE risk in patients with RT-IVCTT. Except hemoglobin, categorically coded serum albumin (OR 0.36, 95% CI 0.17–0.75) was validated as an independent risk factor for VTE.

Conclusions:
This study provided an insight of risk factors contributing to preoperative VTE in patients with RT-IVCTT, which may be beneficial for optimizing strategies to manage VTE in clinical practice.
Consolidating a program theory on how social media supports healthcare providers’ knowledge use in clinical practice: a realist-informed qualitative study
Authors: Zhao Junqiang , Harvey Gillian , Vandyk Amanda , Huang Mandy , Gifford Wendy 
Published: October 2023

Abstract

Objective:
This study aimed to consolidate a program theory, developed from a previous realist review, to further understand how and under what circumstances social media supports healthcare providers’ knowledge use.

Methods:
A realist-informed qualitative study was conducted. We carried out in-depth interviews with 11 participants, including content developers and healthcare providers from China, Australia, and Canada. The data analysis was informed by categorizing and connecting strategies.

Results:
Ten context-mechanism-outcome configurations (CMOs) were developed to consolidate the program theory. Among these, four CMOs confirmed the original CMOs from the realist review, four refined the original ones, and two were new propositions. These 10 CMOs were situated within four interconnected levels of outcomes: social media product, access, engagement, and knowledge use. They considered 1) content developers’ capabilities and capacities, 2) healthcare providers’ increased attention, 3) fulfillment of information needs, 4) access to social influence and support, 5) perception of message value and implementability, 6) behaviour capabilities, self-efficacy, intention, and awareness; and 7) ability to exercise professional autonomy as the key mechanisms. We developed the consolidated program theory based on the 10 CMOs.

Conclusions:
Social media can promote knowledge use by healthcare providers. Future empirical studies drawing on the program theory need to be conducted to further optimize the theoretical understanding.
The Importance of Remodeling the Physiological Mandibular Angle: Mandibular V-Line versus Long Curved Ostectomy
Authors: Ge Han , Zhao Qing , Al-Watary Mohammed Qasem Hezam , Hsu Yuchun , Wei Yiyuan , Wang Yu , Li Jihua 
Published: October 2023

Background:
Numerous surgical options for correcting prominent mandibular angles in East Asian patients have been reported. The objective of this study was to investigate the importance of remodeling physiological mandibular angle by comparing the surgical effects and complications of mandibular V-line ostectomy and long curved ostectomy.

Methods:
A retrospective study was conducted on patients who underwent either mandibular V-line ostectomy (group 1) or long curved ostectomy (group 2). The outcomes were evaluated using computed tomography images in combination with medical records and photographs. Data were collected preoperatively and at 6- to 12-month intervals postoperatively. Mandibular angle, posterior mandibular ramus height, radian of the ostectomy line, and mandibular symmetry, as well as complications, were investigated. FACE-Q reports of facial appearance and psychosocial measures were also compared between the 2 groups.

Results:
All 106 patients showed improved lower facial contours. Although the postoperative mandibular angle (116.67 ± 7.14 versus 118.31 ± 6.80 degrees; P = 0.233) and mandibular symmetry (2.36 ± 1.21 mm versus 2.56 ± 1.19 mm; P = 0.395) were similar in the 2 groups, larger postoperative posterior mandibular height and lower radian of the ostectomy line were observed in group 1 (P < 0.001). Physiological mandibular angle was also remodeled in group 1. The gonial deficiency, more soft-tissue sagging, and significantly lower FACE-Q scores for facial appearance were observed in group 2 (P < 0.001).

Conclusions:
V-line ostectomy is better suited for achieving a more physiological mandibular angle with fewer complications compared with mandibular long curved ostectomy. V-line ostectomy may be the preferred option for mandibular contouring.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Lymphedema-Associated Fibroblasts Are Related to Fibrosis and Stage Progression in Patients and a Murine Microsurgical Model
Authors: Will Patrick A. , Kilian Katja , Bieback Karen , Fricke Fabia , Berner Juan Enrique , Kneser Ulrich , Hirche Christoph 
Published: October 2023

Background:
The driver of secondary lymphedema (SL) progression is chronic inflammation, which promotes fibrosis. Despite advances in preclinical research, a specific effector cell subpopulation as a biomarker for therapy response or stage progression is still missing for SL.

Methods:
Whole skin samples of 35 murine subjects of a microsurgically induced SL model and 12 patients with SL were collected and their fibroblasts were isolated. These lymphedema-associated fibroblasts (LAFs) were cultured in a collagen I-poly-D-lysine 3-dimensional hydrogel to mimic skin conditions. Fibroblasts from nonlymphedema skin were used as negative control and transforming growth factor β (TGF-β)–stimulated fibroblasts were used to recreate profibrotic myofibroblasts. Quantitative immunocytofluorescence confocal microscopy analysis and invasion functional assays were performed in all subpopulations and statistically compared.

Results:
In contrast to normal skin fibroblasts, LAFs exhibit α–smooth muscle actin–positive stress fibers and a reduced number of tight junctions in 3-dimensional hydrogel conditions. The switch from normal E-cadherinhigh phenotype to an N-cadherinhigh-E-cadherinlow morphology suggests epithelial-to-mesenchymal transition for expansion and proliferation. This pathologic behavior of LAF was confirmed by live cell imaging analysis of invasion assays. The significant activation of markers of the TGF-β receptor 2–Smad pathway and collagen synthesis (HSP-47 [heat shock protein 47]) in LAFs supports epithelial-to-mesenchymal transition phenotypic changes and previous findings relating to TGF-β1 and fibrosis with lymphedema.

Conclusions:
A characteristic SL myofibroblast subpopulation was identified and translationally related to fibrosis and TGF-β1–associated stage progression. This SL-related subpopulation was termed LAFs. A comprehensive stage-related characterization is required to validate LAFs as a reliable biomarker for SL disease progression.

Clinical Relevance Statement:
The authors identify a cellular effector for fibrosis and stage progression of secondary lymphedema as a possible biomarker for surgical indication and therapy response.
Analyzing the Costs and Impact of the TakeMeHome Program, a Public–Private Partnership to Deliver HIV Self-Test Kits in the United States
Authors: Shrestha Ram K. , Hecht Jennifer , Chesson Harrell W. 
Published: October 2023

Background:
HIV testing is an entry point to access HIV care and prevention services. Building Healthy Online Communities developed a website (TakeMeHome.org) where participants can order HIV home test kits. The purpose of this study was to analyze the costs and impact of the TakeMeHome program.

Methods:
We estimated the costs of TakeMeHome across all participating jurisdictions for the first year of the program. We estimated program costs using purchase orders and invoices, contracts, and allocation of staff time, and the costs included website design, participant recruitment, administration and overhead, HIV self-test kits, and shipping and handling. Primary outcomes of the analysis were total program cost, cost per HIV test, and cost per new HIV diagnosis.

Results:
The TakeMeHome program distributed 5323 HIV self-tests to 4859 participants over a 12-month period. The total program cost over this period was $314,870. The cost per HIV test delivered was estimated at $59, and the cost per person tested was $65. The program identified 18 confirmed new HIV diagnoses (0.6% positivity) verified with surveillance data in 7 health jurisdictions at $169,890. The cost per confirmed new HIV diagnosis was estimated at $9440.

Conclusions:
The TakeMeHome program delivered HIV self-testing at a reasonable cost, and the program may be a cost-effective use of HIV prevention resources. The public–private partnership can be an effective mechanism to validate HIV diagnoses identified with self-testing and provide HIV prevention and linkage to care services.
Imaging Update for Hereditary Abdominopelvic Neuroendocrine Neoplasms
Authors: Ferreira Dalla Pria Hanna R. , Sharbidre Kedar G. , Virarkar Mayur , Javadi Sanaz , Bhosale Hrishabh , Maxwell Jessica , Lall Chandana , Morani Ajaykumar C. 
Published: October 2023

Abstract
Neuroendocrine neoplasms have shown a linear increase in incidence and prevalence in recent decades, primarily due to improved cross-sectional imaging, expanded use of endoscopic procedures, and advanced genetic analysis. However, diagnosis of hereditary neuroendocrine tumors is still challenging because of heterogeneity in their presentation, the variety of tumor locations, and multiple associated syndromes. Radiologists should be familiar with the spectrum of these tumors and associated hereditary syndromes. Furthermore, as the assessment of multiple tumor elements such as morphology, biochemical markers, and presence of metastatic disease are essential for the treatment plan, conventional anatomic and functional imaging methods are fundamental in managing and surveilling these cases. Our article illustrates the role of different cross-sectional imaging modalities in diagnosing and managing various hereditary abdominopelvic neuroendocrine tumors.
The Association Between Pediatric Readiness and Mortality for Injured Children Treated at US Trauma Centers
Authors: Melhado Caroline , Remick Katherine , Miskovic Amy , Patel Bhavin , Hewes Hilary A. , Newgard Craig D. , Nathens Avery B. , Macias Charles , Gray Lisa , Yorkgitis Brian K. , Dingeldein Michael W. , Jensen Aaron R. 
Published: October 2023

Objective:
To use updated 2021 weighted Pediatric Readiness Score (wPRS) data to identify a threshold level of trauma center emergency department (ED) pediatric readiness.

Background:
Most children in the United States receive initial trauma care at nonpediatric centers. The aim of the National Pediatric Readiness Project (NPRP) was to ensure that all EDs are prepared to provide quality care for children. Trauma centers reporting the highest quartile of wPRS on the 2013 national assessment have been shown to have lower mortality. Significant efforts have been invested to improve pediatric readiness in the past decade.

Study Design:
A retrospective cohort of trauma centers that completed the NPRP 2021 national assessment and contributed to the National Trauma Data Bank (NTDB) from 2019 to 2021 was analyzed. Center-specific observed-to-expected mortality estimates for children (0–15 y) were calculated using Pediatric Trauma Quality Improvement Program models. Deterministic linkage was used for transferred patients to account for wPRS at the initial receiving center. Center-specific mortality odds ratios were then compared across quartiles of wPRS.

Results:
A total of 66,588 children from 630 centers with a median (interquartile range) wPRS of 79 (66–93) were analyzed. The average observed-to-expected odds of mortality [1.02 (0.97–1.06)] for centers in the highest quartile (wPRS≥93) was lower than any of the lowest 3 wPRS quartiles [1.19 (1.14–1.23) (Q1), 1.29 (1.24–1.33) (Q2), and 1.28 (1.19–1.36) (Q3), all P<0.05). The presence of a pediatric-specific quality improvement plan was the domain with the strongest independent association with mortality [standardized beta −0.095 (−0.146 to −0.044)].

Conclusion:
Trauma centers should address gaps in pediatric readiness to include a pediatric-specific quality improvement plan and aim to achieve wPRS ≥93.
Modular multiwell viscoelastic hydrogel platform for two- and three-dimensional cell culture applications
Authors: Skelton Mackenzie L. , Gentry James L. , Astrab Leilani R. , Goedert Joshua A. , Earl E. Brynn , Pham Emily L. , Bhat Tanvi , Caliari Steven R. 
Published: October 2023

AbstractHydrogels have gained significant popularity as model platforms to study the reciprocal interactions between cells and their microenvironment. While hydrogel tools to probe many characteristics of the extracellular space have been developed, fabrication approaches remain challenging and time-consuming, limiting multiplexing or widespread adoption. Thus, we have developed a modular fabrication approach to generate distinct hydrogel microenvironments within 96-well plates for increased throughput of fabrication as well as integration with existing high-throughput assay technologies. This approach enablesin situhydrogel mechanical characterization and was used to generate both elastic and viscoelastic hydrogels across a range of stiffnesses. Additionally, this fabrication method enabled a 3-fold reduction in polymer and up to an 8-fold reduction in fabrication time required per hydrogel replicate. The feasibility of this platform for cell culture applications was demonstrated by measuring both population-level and single cell-level metrics via microplate reader and high-content imaging. Finally, the 96-well hydrogel array was utilized for 3D cell culture, demonstrating the ability to support high cell viability. Together, this work demonstrates a versatile and easily adoptable fabrication approach that can support the ever-expanding tool kit of hydrogel technologies for cell culture applications.
Physiological stress response of koala joeys to visitors
Authors: Pahuja Harsh K. , Bee Izzy , Bee Ali , Narayan Edward J. 
Published: October 2023

AbstractKoala (Phascolarctos cinereus) joey rescues are increasing over the years, and rehabilitation of a joey requires extensive care, close proximity and handling by humans. These novel environments are likely to present a suite of biotic and abiotic stressors during rehabilitation. In this study, we longitudinally monitored the faecal cortisol metabolites (FCMs) of three koala joeys within the context of potential stressors at the Magnetic Island Koala Hospital, Queensland, Australia. A total of 92 faecal samples were analysed for FCMs using a polyclonal R4866 cortisol enzyme-immunoassay which has been previously validated in koalas. The iterative baseline method was used to establish FCM profiles of all individuals, and to identify significant peaks in FCM concentrations. Visitor events were identified and confirmed as an acute stressor based on the FCM profiles of the koala joeys. All three koala joeys elicited a significant rise in FCM concentrations after each visitor encounter. To our knowledge, this is the first study to report on the acute stress response of koala joeys to visitors. We recommend that visitor encounters be kept to a minimum, and perhaps avoided altogether especially for joeys that are being rehabilitated to be released back into the wild.
Tricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants
Authors: Wang Xunan , Marmouzi Ilias , Finnie Peter SB , Støve Svein I , Bucher Meghan L , Lipina Tatiana V , Ramsey Amy J , Miller Gary W , Salahpour Ali 
Published: October 2023

AbstractVesicular monoamine transporter 2 (VMAT2) is an essential transporter that regulates brain monoamine transmission and is important for mood, cognition, motor activity, and stress regulation. However, VMAT2 remains underexplored as a pharmacological target. In this study, we report that tricyclic and tetracyclic antidepressants acutely inhibit, but persistently upregulate VMAT2 activity by promoting VMAT2 protein maturation. Importantly, the VMAT2 upregulation effect was greater in BE(2)-M17 cells that endogenously express VMAT2 as compared to a heterologous expression system (HEK293). The net sustained effect of tricyclics and tetracyclics is an upregulation of VMAT2 activity, despite their acute inhibitory effect. Furthermore, imipramine and mianserin, two representative compounds, also demonstrated rescue of nine VMAT2 variants that cause Brain Vesicular Monoamine Transport Disease (BVMTD). VMAT2 upregulation could be beneficial for disorders associated with reduced monoamine transmission, including mood disorders and BVMTD, a rare but often fatal condition caused by a lack of functional VMAT2. Our findings provide the first evidence that small molecules can upregulate VMAT2 and have potential therapeutic benefit for various neuropsychiatric conditions.
scDILT: a model-based and constrained deep learning framework for single-cell Data Integration, Label Transferring, and clustering
Authors: Lin Xiang , Ren Jianlan , Gao Le , Wei Zhi , Wang Junwen 
Published: October 2023

ABSTRACTThe scRNA-seq technology enables high-resolution profiling and analysis of individual cells. The increasing availability of datasets and advancements in technology have prompted researchers to integrate existing annotated datasets with newly sequenced datasets for a more comprehensive analysis. It is important to ensure that the integration of new datasets does not alter the cell clusters defined in the old/reference datasets. Although several methods have been developed for scRNA-seq data integration, there is currently a lack of tools that can simultaneously achieve the aforementioned objectives. Therefore, in this study, we have introduced a novel tool called scDILT, which leverages a conditional autoencoder and deep embedding clustering to effectively remove batch effects among different datasets. Moreover, scDILT utilizes homogeneous constraints to preserve the cell-type/clustering patterns observed in the reference datasets, while employing heterogeneous constraints to map cells in the new datasets to the annotated cell clusters in the reference datasets. We have conducted extensive experiments to demonstrate that scDILT outperforms other methods in terms of data integration, as confirmed by evaluations on simulated and real datasets. Furthermore, we have shown that scDILT can be successfully applied to integrate multi-omics single-cell datasets. Based on these findings, we conclude that scDILT holds great promise as a tool for integrating single-cell datasets derived from different batches, experiments, times, or interventions.