bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuation of Gender-affirming Hormones Among Transgender Adolescents and Adults
Authors: Roberts Christina M , Klein David A , Adirim Terry A , Schvey Natasha A , Hisle-Gorman Elizabeth 
Published: April 2022

Abstract

Introduction
Concerns about future regret and treatment discontinuation have led to restricted access to gender-affirming medical treatment for transgender and gender-diverse (TGD) minors in some jurisdictions. However, these concerns are merely speculative because few studies have examined gender-affirming hormone continuation rates among TGD individuals.

Methods
We performed a secondary analysis of 2009 to 2018 medical and pharmacy records from the US Military Healthcare System. We identified TGD patients who were children and spouses of active-duty, retired, or deceased military members using International Classification of Diseases-9/10 codes. We assessed initiation and continuation of gender-affirming hormones using pharmacy records. Kaplan-Meier and Cox proportional hazard analyses estimated continuation rates.

Results
The study sample included 627 transmasculine and 325 transfeminine individuals with an average age of 19.2 ± 5.3 years. The 4-year gender-affirming hormone continuation rate was 70.2% (95% CI, 63.9-76.5). Transfeminine individuals had a higher continuation rate than transmasculine individuals 81.0% (72.0%-90.0%) vs 64.4% (56.0%-72.8%). People who started hormones as minors had higher continuation rate than people who started as adults 74.4% (66.0%-82.8%) vs 64.4% (56.0%-72.8%). Continuation was not associated with household income or family member type. In Cox regression, both transmasculine gender identity (hazard ratio, 2.40; 95% CI, 1.50-3.86) and starting hormones as an adult (hazard ratio, 1.69; 95% CI, 1.14-2.52) were independently associated with increased discontinuation rates.

Discussion
Our results suggest that &gt;70% of TGD individuals who start gender-affirming hormones will continue use beyond 4 years, with higher continuation rates in transfeminine individuals. Patients who start hormones, with their parents’ assistance, before age 18 years have higher continuation rates than adults.
Burnout Syndrome Among Anesthesia Providers Working in Public Hospitals in Rwanda: A Cross-Sectional Survey
Authors: Tuyishime Eugene , McIsaac Daniel I. , Mumbwe Mbangu C. , Ruhato Banguti Paulin , Mvukiyehe Jean Paul , Nzarora Josue , Bould M. Dylan 
Published: April 2022

BACKGROUND:
Many studies address anesthesia provider burnout in high-income countries; however, there is a paucity of data on burnout for anesthesia providers in low-income countries (LICs). Our objectives were (1) to evaluate the prevalence of burnout among anesthesia providers in Rwandan hospitals and (2) to determine factors associated with burnout among anesthesia providers in Rwandan hospitals.

METHODS:
A questionnaire was sent to selected Rwandan anesthesia providers working in public hospitals. The questionnaire assessed burnout using the Maslach Burnout Inventory Human Services Survey, a validated 22-item survey used to measure burnout among health professionals. Sociodemographic and work-related factors found to be associated with burnout were also assessed using logistic regression in a Bayesian framework to estimate odds ratios (OR) and associated credible intervals (CrIs).

RESULTS:
Surveys were distributed to 137 Rwandan anesthesia providers; 99 (72.3%) were returned. Sixty-six (67%) respondents were nonphysician anesthesia providers. Burnout was present in 26 of 99 (26.3%) participants (95% confidence interval [CI], 17.9–36.1). When considering weakly informative priors, we found a 99% probability that not having the right team (OR, 5.36%; 95 CrI, 1.34–23.53) and the frequency of seeing patients with negative outcomes such as death or permanent disability (OR, 9.62; 95% CrI, 2.48–42.84) were associated with burnout.

CONCLUSIONS:
In a cross-sectional survey of anesthesia providers in Rwanda, more than a quarter of respondents met the criteria for burnout. Lacking the right team and seeing negative outcomes were associated with higher burnout rate. These identified factors should be addressed to prevent the negative consequences of burnout, such as poor patient outcomes.
Phenotype assessment for neurodegenerative murine models with ataxia and application to Niemann–Pick disease, type C1
Authors: Yerger Julia , Cougnoux Antony C. , Abbott Craig B. , Luke Rachel , Clark Tannia S. , Cawley Niamh X. , Porter Forbes D. , Davidson Cristin D. 
Published: April 2022

ABSTRACT
Identifying meaningful predictors of therapeutic efficacy from preclinical studies is challenging. However, clinical manifestations occurring in both patients and mammalian models offer significant translational value. Many neurological disorders, including inherited, metabolic Niemann–Pick disease, type C (NPC), exhibit ataxia. Both individuals with NPC and murine models manifest ataxia, and investigational therapies impacting this phenotype in mice have been reported to slow disease progression in patients (e.g. miglustat, intrathecal 2-hydroxypropyl-beta-cyclodextrin, and acetyl-L-leucine). Reproducible phenotypic scoring of animal models can facilitate comparisons between genotypes, sexes, disease course, and therapies. Previously, other groups have developed a composite phenotypic scoring system (CPSS), which was subsequently used to distinguish strain-dependent phenotypes and, with modifications, to evaluate potential therapies. However, high inter-rater reliability is paramount to widespread use. We have created a comprehensive, easy-to-follow phenotypic assessment based on the CPSS and have verified its reproducibility using murine models of NPC disease. Application of this scoring system is not limited to NPC disease and may be applicable to other models of neurodegeneration exhibiting motor incoordination, thereby increasing its utility in translational studies.
Characterization of human nasal organoids from chronic rhinosinusitis patients
Authors: Ramezanpour Mahnaz , Bolt Harrison , Hon Karen , Shaghayegh Gohar , Rastin Hadi , Fenix Kevin Aaron , Psaltis Alkis James , Wormald Peter-John , Vreugde Sarah 
Published: April 2022

ABSTRACT
Patient-derived organoids grown in three-dimensional cultures provide an excellent platform for phenotypic high-throughput screening and drug-response research. Organoid technology has been applied to study stem cell biology and various human pathologies. This study investigates the characteristics and cellular morphology of organoids derived from primary human nasal epithelial cells (HNECs) of chronic rhinosinusitis (CRS) patients. Nasal organoids were cultured up to 20 days and morphological, cell composition and functional parameters were measured by immunofluorescence, RT-qPCR, western blot and FACS analysis. The results showed that nasal organoids expressed the stem cell marker leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), and markers for apical junction genes, goblet cells and ciliated cells. Moreover, we were able to regrow and expand the nasal organoids well after freezing and thawing. This study provides an effective and feasible method for development of human nasal organoids, suitable for the phenotypic high-throughput screening and drug response research.
Defining the Hoxb8 cell lineage during murine definitive hematopoiesis
Authors: Van Deren Donn A. , De Shrutokirti , Xu Ben , Eschenbacher Kayla M. , Zhang Shuhua , Capecchi Mario R. 
Published: April 2022

ABSTRACT
Previously, we have demonstrated that a subpopulation of microglia, known as Hoxb8 microglia, is derived from the Hoxb8 lineage during the second wave (E8.5) of yolk sac hematopoiesis, whereas canonical non-Hoxb8 microglia arise from the first wave (E7.5). Hoxb8 microglia have an ontogeny distinct from non-Hoxb8 microglia. Dysfunctional Hoxb8 microglia cause the acquisition of chronic anxiety and an obsessive-compulsive spectrum-like behavior, trichotillomania, in mice. The nature and fate of the progenitors generated during E8.5 yolk sac hematopoiesis have been controversial. Herein, we use the Hoxb8 cell lineage reporter to define the ontogeny of hematopoietic cells arising during the definitive waves of hematopoiesis initiated in the E8.5 yolk sac and aorta-gonad-mesonephros (AGM) region. Our murine cell lineage analysis shows that the Hoxb8 cell lineage reporter robustly marks erythromyeloid progenitors, hematopoietic stem cells and their progeny, particularly monocytes. Hoxb8 progenitors and microglia require Myb function, a hallmark transcription factor for definitive hematopoiesis, for propagation and maturation. During adulthood, all immune lineages and, interestingly, resident macrophages in only hematopoietic/lymphoid tissues are derived from Hoxb8 precursors. These results illustrate that the Hoxb8 lineage exclusively mirrors murine definitive hematopoiesis.
Lmo7 recruits myosin II heavy chain to regulate actomyosin contractility and apical domain size inXenopusectoderm
Authors: Matsuda Miho , Chu Chih-Wen , Sokol Sergei Y. 
Published: April 2022

ABSTRACTApical constriction, or a reduction in size of the apical domain, underlies many morphogenetic events during development. Actomyosin complexes play an essential role in apical constriction; however, the detailed analysis of molecular mechanisms is still pending. Here, we show that Lim domain only protein 7 (Lmo7), a multidomain adaptor at apical junctions, promotes apical constriction in the Xenopus superficial ectoderm, whereas apical domain size increases in Lmo7-depleted cells. Lmo7 is primarily localized at apical junctions and promotes the formation of the dense circumferential actomyosin belt. Strikingly, Lmo7 binds non-muscle myosin II (NMII) and recruits it to apical junctions and the apical cortex. This NMII recruitment is essential for Lmo7-mediated apical constriction. Lmo7 knockdown decreases NMIIA localization at apical junctions and delays neural tube closure in Xenopus embryos. Our findings suggest that Lmo7 serves as a scaffold that regulates actomyosin contractility and apical domain size.
Revisiting the role of Notch in nephron segmentation confirms a role for proximal fate selection during mouse and human nephrogenesis
Authors: Duvall Kathryn , Crist Lauren , Perl Alison J. , Pode Shakked Naomi , Chaturvedi Praneet , Kopan Raphael 
Published: April 2022

ABSTRACT
Notch signaling promotes maturation of nephron epithelia, but its proposed contribution to nephron segmentation into proximal and distal domains has been called into doubt. We leveraged single cell and bulk RNA-seq, quantitative immunofluorescent lineage/fate tracing, and genetically modified human induced pluripotent stem cells (iPSCs) to revisit this question in developing mouse kidneys and human kidney organoids. We confirmed that Notch signaling is needed for maturation of all nephron lineages, and thus mature lineage markers fail to detect a fate bias. By contrast, early markers identified a distal fate bias in cells lacking Notch2, and a concomitant increase in early proximal and podocyte fates in cells expressing hyperactive Notch1 was observed. Orthogonal support for a conserved role for Notch signaling in the distal/proximal axis segmentation is provided by the demonstration that nicastrin (NCSTN)-deficient human iPSC-derived organoids differentiate into TFA2B+ distal tubule and CDH1+ connecting segment progenitors, but not into HNF4A+ or LTL+ proximal progenitors.
The clinical manifestations, molecular mechanisms and treatment of craniosynostosis
Authors: Stanton Eloise , Urata Mark , Chen Jian-Fu , Chai Yang 
Published: April 2022

ABSTRACT
Craniosynostosis is a major congenital craniofacial disorder characterized by the premature fusion of cranial suture(s). Patients with severe craniosynostosis often have impairments in hearing, vision, intracranial pressure and/or neurocognitive functions. Craniosynostosis can result from mutations, chromosomal abnormalities or adverse environmental effects, and can occur in isolation or in association with numerous syndromes. To date, surgical correction remains the primary treatment for craniosynostosis, but it is associated with complications and with the potential for re-synostosis. There is, therefore, a strong unmet need for new therapies. Here, we provide a comprehensive review of our current understanding of craniosynostosis, including typical craniosynostosis types, their clinical manifestations, cranial suture development, and genetic and environmental causes. Based on studies from animal models, we present a framework for understanding the pathogenesis of craniosynostosis, with an emphasis on the loss of postnatal suture mesenchymal stem cells as an emerging disease-driving mechanism. We evaluate emerging treatment options and highlight the potential of mesenchymal stem cell-based suture regeneration as a therapeutic approach for craniosynostosis.
Chaperone-mediated assembly of the proteasome core particle – recent developments and structural insights
Authors: Schnell Helena M. , Walsh Richard M. , Rawson Shaun , Hanna John 
Published: April 2022

ABSTRACT
Much of cellular activity is mediated by large multisubunit complexes. However, many of these complexes are too complicated to assemble spontaneously. Instead, their biogenesis is facilitated by dedicated chaperone proteins, which are themselves excluded from the final product. This is the case for the proteasome, a ubiquitous and highly conserved cellular regulator that mediates most selective intracellular protein degradation in eukaryotes. The proteasome consists of two subcomplexes: the core particle (CP), where proteolysis occurs, and the regulatory particle (RP), which controls substrate access to the CP. Ten chaperones function in proteasome biogenesis. Here, we review the pathway of CP biogenesis, which requires five of these chaperones and proceeds through a highly ordered multistep pathway. We focus on recent advances in our understanding of CP assembly, with an emphasis on structural insights. This pathway of CP biogenesis represents one of the most dramatic examples of chaperone-mediated assembly and provides a paradigm for understanding how large multisubunit complexes can be produced.
Combination of UNet++ and ResNeSt to classify chronic inflammation of the choledochal cystic wall in patients with pancreaticobiliary maljunction
Authors: Guo Wan-liang , Geng An-kang , Geng Chen , Wang Jian , Dai Ya-kang 
Published: April 2022

Objectives: The aim of this study was to establish an automatic classification model for chronic inflammation of the choledoch wall using deep learning with CT images in patients with pancreaticobiliary maljunction (PBM). Methods: CT images were obtained from 76 PBM patients, including 61 cases assigned to the training set and 15 cases assigned to the testing set. The region of interest (ROI) containing the choledochal lesion was extracted and segmented using the UNet++ network. The degree of severity of inflammation in the choledochal wall was initially classified using the ResNeSt network. The final classification result was determined per decision rules. Grad-CAM was used to explain the association between the classification basis of the network and clinical diagnosis. Results: Segmentation of the lesion on the common bile duct wall was roughly obtained with the UNet++ segmentation model and the average value of Dice coefficient of the segmentation model in the testing set was 0.839 ± 0.150, which was verified through fivefold cross-validation. Inflammation was initially classified with ResNeSt18, which resulted in accuracy = 0.756, sensitivity = 0.611, specificity = 0.852, precision = 0.733, and area under curve (AUC) = 0.711. The final classification sensitivity was 0.8. Grad-CAM revealed similar distribution of inflammation of the choledochal wall and verified the inflammation classification. Conclusions: By combining the UNet++ network and the ResNeSt network, we achieved automatic classification of chronic inflammation of the choledoch in PBM patients and verified the robustness through cross-validation performed five times. This study provided an important basis for classification of inflammation severity of the choledoch in PBM patients. Advances in knowledge: We combined the UNet++ network and the ResNeSt network to achieve automatic classification of chronic inflammation of the choledoch in PBM. These results provided an important basis for classification of choledochal inflammation in PBM and for surgical therapy.
COVID-19 pneumonia chest radiographic severity score: variability assessment among experienced and in-training radiologists and creation of a multireader composite score database for artificial intelligence algorithm development
Authors: van Assen Marly , Zandehshahvar Mohammadreza , Maleki Hossein , Kiarashi Yashar , Arleo Timothy , Stillman Arthur E. , Filev Peter , Davarpanah Amir H. , Berkowitz Eugene A. , Tigges Stefan , Lee Scott J. , Vey Brianna L. , Adibi Ali , De Cecco Carlo N. 
Published: April 2022

Objective:
The purpose was to evaluate reader variability between experienced and in-training radiologists of COVID-19 pneumonia severity on chest radiograph (CXR), and to create a multireader database suitable for AI development.

Methods:
In this study, CXRs from polymerase chain reaction positive COVID-19 patients were reviewed. Six experienced cardiothoracic radiologists and two residents classified each CXR according to severity. One radiologist performed the classification twice to assess intraobserver variability. Severity classification was assessed using a 4-class system: normal (0), mild (1), moderate (2), and severe (3). A median severity score (Rad Med) for each CXR was determined for the six radiologists for development of a multireader database (XCOMS). Kendal Tau correlation and percentage of disagreement were calculated to assess variability.

Results:
A total of 397 patients (1208 CXRs) were included (mean age, 60 years SD ± 1), 189 men). Interobserver variability between the radiologists ranges between 0.67 and 0.78. Compared to the Rad Med score, the radiologists show good correlation between 0.79–0.88. Residents show slightly lower interobserver agreement of 0.66 with each other and between 0.69 and 0.71 with experienced radiologists. Intraobserver agreement was high with a correlation coefficient of 0.77. In 220 (18%), 707 (59%), 259 (21%) and 22 (2%) CXRs there was a 0, 1, 2 or 3 class-difference. In 594 (50%) CXRs the median scores of the residents and the radiologists were similar, in 578 (48%) and 36 (3%) CXRs there was a 1 and 2 class-difference.

Conclusion:
Experienced and in-training radiologists demonstrate good inter- and intraobserver agreement in COVID-19 pneumonia severity classification. A higher percentage of disagreement was observed in moderate cases, which may affect training of AI algorithms.

Advances in knowledge:
Most AI algorithms are trained on data labeled by a single expert. This study shows that for COVID-19 X-ray severity classification there is significant variability and disagreement between radiologist and between residents.
Alteration in central vascular and cognitive functions during simulated work conditions in males – a secondary analysis from a randomised controlled trial
Authors: Shruthi P Poovitha , Chandran M Obhuli , Chandrasekaran Baskaran , K. Vaishali , Sukumar Suresh , Kadavigere Rajagopal 
Published: April 2022

Background: Alteration in the central vascular hemodynamics is speculated to influence cognitive functions, including executive functions in young adults. Prolonged sitting is associated with compromised central vascular functions, which activity micro-breaks could mitigate. However, the association between the carotid vascular hemodynamic alteration and the executive functions is yet to be explored. Methods: We administered a randomised controlled trial investigating the effects of various intensities' micro-breaks on central vascular and cognitive functions during simulated work conditions for four hours. The carotid artery hemodynamics and cognitive functions were measured by Duplex ultrasound at 0th, 2nd and 4th hour and computer-based Flanker tests at 0th, 1st, 2nd, 3rd and 4th hour of visit days, respectively. From the randomised controlled trial, we extracted the secondary data of carotid artery hemodynamics and cognitive functions change at the 4th hour from the baseline and analysed for any relation. Results: Though we observed linear relation between the carotid artery hemodynamics and the executive functions, the relation was not statistically significant. we found a significant reduction in carotid artery diameter during prolonged sitting (0.03 cm [95%CI 0.01, 0.05]), velocity (10.35 cm/s [95%CI -2.85, 17.86]) and shear rate during interrupted sitting (174.39 [95%CI 65.67, 283.11]) We found increased accuracy during prolonged sitting (12.7% [95%CI 0.66, 24.81]) and sitting with light-intensity activity breaks (6.92% [95%CI 1.39, 12.44]). We did not find any significant relation between the change in central vascular functions (carotid artery diameter, velocity, shear rate and blood flow) and the cognitive functions during three different work conditions. Conclusion: Though a significant relation between carotid artery function and cognitive function could not be established, microbreaks can mitigate the vascular and cognitive risks associated with prolonged sitting.
The Edgeworth Conjecture with Small Coalitions and Approximate Equilibria in Large Economies
Authors: Barman Siddharth , Echenique Federico 
Published: April 2022

We revisit the connection between bargaining and equilibrium in exchange economies and study its algorithmic implications. We consider bargaining outcomes to be allocations that cannot be blocked (i.e., profitably retraded) by coalitions of small size, and show that these allocations must be approximate Walrasian equilibria. Our results imply that deciding whether an allocation is approximately Walrasian can be done in polynomial time, even in economies for which finding an equilibrium is known to be computationally hard. Funding: This work was supported by National Science Foundation [Grants CNS-1518941 and SES-1558757] and S. Barman gratefully acknowledges the support from the Science and Engineering Research Board [Grant SB/S2/RJN-128/2015].