bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in patients with primary biliary cholangitis
Authors: Saeki Chisato , Oikawa Tsunekazu , Kanai Tomoya , Nakano Masanori , Torisu Yuichi , Sasaki Nobuyuki , Abo Masahiro , Saruta Masayuki , Tsubota Akihito 
Published: June 2020

Aim
Bone disorders are serious complications in patients with primary biliary cholangitis (PBC), especially in postmenopausal female patients. Given that osteoporosis interrelates closely with sarcopenia, the concept of osteosarcopenia (coexistence of the two complications) has been established. This study aimed to investigate the relationship between osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in PBC patients.

Methods
This study involved 117 consecutive PBC patients (21 males and 96 females). Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Sarcopenia was diagnosed according to the Japan Society of Hepatology assessment criteria.

Results
Of the 117 patients, 33 (28.2%), 27 (23.1%), 21 (17.9%), and 18 (15.4%) had osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia, respectively. Multivariate analysis identified sarcopenia as a significant, independent risk factor associated with osteoporosis in all and female patients [odds ratio (OR) = 4.126, P = 0.018; OR = 6.510, P = 0.001, respectively], and vice versa (OR = 3.420, P = 0.040; OR = 4.012, P = 0.026, respectively). The skeletal muscle mass index and handgrip strength were significantly correlated with the BMD of the lumbar spine, femoral neck, and total hip (r = 0.46–0.59, P < 0.001). Patients with osteosarcopenia had significantly higher prevalence of vertebral fracture (10/18; 55.6%) than those without both osteoporosis and sarcopenia (5/75; 6.7%).

Conclusion
We demonstrated the prevalence of osteoporosis, sarcopenia, vertebral fracture, and osteosarcopenia in PBC, and noted that these complications interrelated closely with each other. Comprehensive assessment and treatment strategies for bone and muscle disorders are essential for PBC patients.
Protocol Optimization and Implementation of Dual-Energy and Dual-Source Computed Tomography in Clinical Practice: Field of View, Speed, or Material Separation?
Authors: Pedersen Christian K. , Mackey Justin E. , Teytelboym Oleg M. 
Published: June 2020

Abstract
Clinical use of dual-energy computed tomography (DECT) and dual-source computed tomography (DSCT) has been well established for more than a decade. Improved software and decreased postprocessing time have increased the advantages and availability of DECT and DSCT imaging. In this article, we will provide a practical guide for implementation of DECT and DSCT in clinical practice and discuss automated processing and selection of CT protocols in neurologic, cardiothoracic, vascular, body, and musculoskeletal imaging.
Thai Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Outcomes and Risk Factors for Mortality
Authors: Intapiboon Porntip , Siripaitoon Boonjing 
Published: June 2020

Background/Objective
Patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) have an increased risk of premature death. Different subtypes, predictors, and ethnicities may affect the overall survival. However, the overall survival of Thai AAV patients has not been reported. We examined the mortality and prognosis of these patients.

Methods
This medical record review study included adult AAV patients, admitted to Songklanagarind Hospital from 2007 to 2017. Antineutrophil cytoplasmic antibody–associated vasculitis was diagnosed according to the 1990 American College of Rheumatology criteria or 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Follow-up data were collected until June 2018. Prognostic factors and overall survival were analyzed.

Results
Among 57 AAV patients, mean (SD) age was 49.3 (16.1) years. Microscopic polyangiitis was the predominant diagnosis (42%). Kidneys (67%) and lungs (65%) were the 2 most affected organs. Initial Birmingham Vasculitis Activity Score (BVAS) greater than 20 was found in 61% of patients. Corticosteroids were the main drugs, and 58% received cyclophosphamide during the induction phase. Overall mean survival time was 38.8 (42.2) months. Patient survival was 91% and 82% at 1 and 6 months, respectively. One-year and 5-year survival rates were 78% and 63%, respectively. Univariate analysis showed that initial BVAS of greater than 20, neutrophil-to-lymphocyte ratio greater than 5.8, and need for invasive ventilator were significant predictors of mortality. Initial BVAS of greater than 20 was the only predictor of death in multivariate analyses (odds ratio, 4.22; 95% confidence interval, 1.01–17.63; p = 0.048).

Conclusions
The mortality rate of Thai AAV patients is high and strongly related to high disease activity. An early recognition and referral system are warranted to improve outcomes.
Detection of Unsuspected Coronavirus Disease 2019 Cases by Computed Tomography and Retrospective Implementation of the Radiological Society of North America/Society of Thoracic Radiology/American College of Radiology Consensus Guidelines
Authors: Lang Min , Som Avik , Mendoza Dexter P. , Flores Efren J. , Li Matthew D. , Shepard Jo-Anne O. , Little Brent P. 
Published: June 2020

Purpose:
The purpose of this article was to report the utility of computed tomography (CT) for detecting unsuspected cases of Coronavirus disease 2019 (COVID-19) and the utility of the Radiological Society of North America (RSNA)/Society of Thoracic Radiology (STR)/American College of Radiology (ACR) consensus guidelines for COVID-19 reporting.

Materials and Methods:
A total of 22 patients of the 156 reverse transcriptase polymerase chain reaction confirmed COVID-19 patients who were hospitalized between March 27, 2020 and March 31, 2020 at our quaternary care academic medical center and who underwent CT imaging within 1 week of admission were included in this retrospective study. Demographics and clinical data were extracted from the electronic medical record system. Two thoracic radiologists independently categorized each CT study on the basis of RSNA/STR/ACR consensus guidelines. Disagreement in categorization was resolved by consensus discussion with a third thoracic radiologist.

Results:
At the time of imaging, 16 patients (73%) were suspected of COVID-19, and 6 patients (27%) were not. Common symptoms at presentation were fever (73%), cough (77%), and gastrointestinal symptoms (59%). An overall 63% of suspected COVID-19 patients exhibited shortness of breath, whereas 0 unsuspected COVID-19 patients did (P=0.02). On the basis of the RSNA consensus guidelines, 68%, 18%, 9%, and 5% of studies were categorized as “typical appearance,” “indeterminate appearance,” “atypical appearance,” and “negative for pneumonia,” respectively. There was no difference of category distribution between suspected and unsuspected COVID-19 patients (P=0.20), with “typical appearance” being the most prevalent in both (69% vs. 67%, respectively).

Conclusions:
It is important to recognize imaging features of COVID-19 pneumonia even in unsuspected patients. Implementation of the RSNA/STR/ACR consensus guidelines may increase consistency of reporting and convey the level of suspicion for COVID-19 to other health care providers, with “typical appearance” especially warranting further attention.
Recurrence After Stopping Maintenance Electroconvulsive Therapy
Authors: Cabelguen Clémence , Caillet Pascal , Poulet Emmanuel , Szekely David , Desmidt Thomas , Pichot Anne , Vanelle Jean-Marie , Sauvaget Anne , Bulteau Samuel 
Published: June 2020

Objectives
Relapses and recurrence remain the greatest risks posed by patients with severe mood disorders after discontinuation of electroconvulsive therapy (ECT). To date, despite a wide range of literature on ECT, little is known about the rate of recurrence of depression after maintenance ECT (mECT) discontinuation specifically. This study sought to address this lacuna, confronting literature data to the results of a retrospective case study.

Methods
A comprehensive review was conducted, followed by a retrospective analysis of 18 cases of mECT discontinuation between January 2011 and June 2016 involving patients with affective disorders.

Results
The comprehensive review revealed that only 3 studies have assessed recurrence rate after c/mECT discontinuation. In our retrospective analysis, mean (SD) mECT duration was 12.69 (12.16) months. A new mood event (usually a depressive state) was observed in 50% of the cases, and 44% of those recurrences occurred during the first 6 months after discontinuation.

Discussion
Given that high recurrence rates are observed after mECT discontinuation, the authors discuss the advantages of long-term mECT and the choice of concomitant pharmacotherapy for severe and complex affective disorders.
Building memories on prior knowledge: behavioral and fMRI evidence of impairment in early Alzheimer’s Disease
Authors: Jonin Pierre-Yves , Duché Quentin , Bannier Elise , Corouge Isabelle , Ferré Jean-Christophe , Belliard Serge , Barillot Christian , Barbeau Emmanuel J. 
Published: June 2020

AbstractImpaired memory is a hallmark of prodromal Alzheimer’s Disease (AD). Prior knowledge associated with the memoranda has proved to have a powerful effect on memory in healthy subjects. Yet, barely nothing is known about its effect in early AD. We used functional MRI to ask whether prior knowledge enhanced memory encoding in early AD and whether the nature of prior knowledge mattered. Early AD patients and healthy controls underwent a task-based fMRI experiment, being scanned while learning face-scene associations. Famous faces carried Pre-Experimental Knowledge (PEK) while unknown faces repeatedly familiarized prior to learning carried Experimental Knowledge (EK). As expected, PEK increased subsequent memory in healthy elderly. However, patients did not benefit from PEK. Partly non-overlapping brain networks supported PEK vs. EK encoding in healthy controls. Patients displayed impaired activation in a right subhippocampal region where activity predicted successful associative memory formation of PEK stimuli. These findings call for a thorough consideration of how prior knowledge impacts learning and suggest a possible underestimation of the extent of associative memory impairment in early AD.HighlightsLearning is impaired in prodromal AD, but we currently ignore whether prior knowledge available at encoding promotes learning in AD as it does in healthy controls.Patients with AD failed to benefit from pre-experimental prior knowledge (famous faces) by comparison with experimental knowledge (unknown but familiarized faces).fMRI responses at study revealed distinct networks underlying associative encoding for both pre-experimental and experimental knowledge.A subsequent memory effect found in control subjects for associations carrying pre-experimental knowledge in the right subhippocampal structures, including the perirhinal cortex, was absent in patients.Pre-experimental knowledge-based associative encoding relies on brain regions specifically targeted by early tau pathology.Using unfamiliar materials to probe memory in early AD might underestimate learning impairment.
The MRi-Share database: brain imaging in a cross-sectional cohort of 1,870 university students
Authors: Tsuchida Ami , Laurent Alexandre , Crivello Fabrice , Petit Laurent , Joliot Marc , Pepe Antonietta , Beguedou Naka , Gueye Marie-Fateye , Verrecchia Violaine , Nozais Victor , Zago Laure , Tzourio-Mazoyer Nathalie , Mellet Emmanuel , Debette Stephanie , Tzourio Christophe , Mazoyer Bernard 
Published: June 2020

AbstractWe report on MRi-Share, a multi-modal brain MRI database acquired in a unique sample of 1,870 young healthy adults, aged 18 to 35 years, while undergoing university-level education. MRi-Share contains structural (T1 and FLAIR), diffusion (multispectral), susceptibility weighted (SWI), and resting-state functional imaging modalities. Here, we described the contents of these different neuroimaging datasets and the processing pipelines used to derive brain phenotypes, as well as how quality control was assessed. In addition, we present preliminary results on associations of some of these brain image-derived phenotypes at the whole brain level with both age and sex, in the subsample of 1,722 individuals aged less than 26 years. We demonstrate that the post-adolescence period is characterized by changes in both structural and microstructural brain phenotypes. Grey matter cortical thickness, surface area and volume were found to decrease with age, while white matter volume shows increase. Diffusivity, either radial or axial, was found to robustly decrease with age whereas fractional anisotropy only slightly increased. As for the neurite orientation dispersion and densities, both were found to increase with age. The isotropic volume fraction also showed a slight increase with age. These preliminary findings emphasize the complexity of changes in brain structure and function occurring in this critical period at the interface of late maturation and early aging.
Prefusion spike protein stabilization through computational mutagenesis
Authors: Zhang Dong Yan , Wang Jian , Dokholyan Nikolay V. 
Published: June 2020

ABSTRACTA novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines’ developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants.
HNRNPM controls circRNA biogenesis and splicing fidelity to sustain prostate cancer cell fitness
Authors: Ho Jessica SY , Low Diana , Schwarz Megan , Incarnato Danny , Gay Florence , Tabaglio Tommaso , Zhang Jingxian , Wollman Heike , Chen Leilei , An Omer , Chan Tim Hon Man , Hickman Alexander Hall , Zheng Simin , Roudko Vladimir , Chen Sujun , Ahmed Musaddeque , He Housheng Hansen , Greenbaum Benjamin D. , Marazzi Ivan , Serresi Michela , Gargiulo Gaetano , Oliviero Salvatore , Wee Dave Keng Boon , Guccione Ernesto 
Published: June 2020

ABSTRACTCancer cells are differentially dependent on the splicing machinery compared to normal untransformed cells. The splicing machinery thus represents a potential therapeutic target in cancer. To identify splicing factors important for prostate cancer cell (PCa) cell growth, we performed a parallel pooled shRNA screen onin vitropassaged cells andin vivoxenografted PCa tumor lines. Our screen revealed HNRNPM as a potential regulator of PCa cell growth. RNA- and eCLIP-sequencing data suggest that HNRNPM is bound to transcripts of key homeostatic genes and that loss of HNRNPM binding in a subset of these genes results in aberrant exon inclusion and exon back-splicing events in target transcripts. In both linear and circular mis-spliced transcripts, HNRNPM appears to preferentially bind to GU-rich elements in long flanking proximal introns. Mimicry of HNRNPM dependent linear splicing events using splice-switching antisense oligonucleotides (SSOs) was sufficient to inhibit cell growth in HNRNPM expressing cells. This suggests that prostate cancer cell dependence on HNRNPM is likely a result of mis-splicing of key homeostatic coding and non-coding genes. Taken together, our data reveal a role for HNRNPM in supporting prostate cancer cell fitness, and also as a potential therapeutic target in PCa.
Mechanical control of tissue shape and morphogenetic flows during vertebrate body axis elongation
Authors: Banavar Samhita P. , Carn Emmet K. , Rowghanian Payam , Stooke-Vaughan Georgina , Kim Sangwoo , Campàs Otger 
Published: June 2020

ABSTRACTShaping embryonic tissues into their functional morphologies requires cells to control the physical state of the tissue in space and time. While regional variations in cellular forces or cell proliferation have been typically assumed to be the main physical factors controlling tissue morphogenesis, recent experiments have revealed that spatial variations in the tissue physical (fluid/solid) state play a key role in shaping embryonic tissues. Here we theoretically study how the regional control of fluid and solid tissue states guides morphogenetic flows to shape the extending vertebrate body axis. Our results show that both the existence of a fluid-to-solid tissue transition along the anteroposterior axis and the tissue surface tension determine the shape of the tissue and its ability to elongate unidirectionally, with large tissue tensions preventing unidirectional elongation and promoting blob-like tissue expansions. We predict both the tissue morphogenetic flows and stresses that enable unidirectional axis elongation. Our results show the existence of a sharp transition in the structure of morphogenetic flows, from a flow with no vortices to a flow with two counter-rotating vortices, caused by a transition in the number and location of topological defects in the flow field. Finally, comparing the theoretical predictions to quantitative measurements of both tissue flows and shape during zebrafish body axis elongation, we show that the observed morphogenetic events can be explained by the mere existence of a fluid-to-solid tissue transition along the anteroposterior axis. These results highlight the role of spatiotemporally-controlled fluid-to-solid transitions in the tissue state as a physical mechanism of embryonic morphogenesis.
Low Dose Hyperoxia Primes Airways for Fibrosis in Mice after Influenza A Infection
Authors: Dylag Andrew M. , Haak Jeannie , Warren Rachel , Yee Min , Pryhuber Gloria S. , O’Reilly Michael A. 
Published: June 2020

AbstractIt is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection suggesting neonatal oxygen may have induced hidden molecular changes that may prime to the lung for disease. We discovered that thrombospondin-1 (TSP-1) is elevated in adult mice exposed to high-dose neonatal hyperoxia that is known to cause alveolar simplification and fibrotic lung disease following IAV infection. TSP-1 was also elevated in a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that we recently reported causes a transient change in lung function that resolves by 8 weeks of age. Elevated TSP-1 was also identified in human autopsy samples of BPD-affected former preterm infants. Consistent with TSP-1 being a master TGFβ regulator, an early transient activation of TGFβ signaling, increased airway hyperreactivity, and peribronchial inflammation and fibrosis were seen when 40×8 mice were infected with IAV, which was not seen in infected room air controls. These findings reveal low dose of neonatal hyperoxia that does not affect lung function or structure may still change expression of genes, such as TSP-1, that may prime the lung for disease following respiratory viral infections, and may help explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.
Conclusive Identification of Senescent T Cells Reveals Their Abundance in Aging Humans
Authors: Martínez-Zamudio Ricardo Iván , Dewald Hannah K. , Vasilopoulos Themistoklis , Gittens-Williams Lisa , Fitzgerald-Bocarsly Patricia , Herbig Utz 
Published: June 2020

ABSTRACTAging leads to a progressive functional decline of the immune system, which renders the elderly increasingly susceptible to disease and infection. The degree to which immune cell senescence contributes to this functional decline, however, remains unclear since methods to accurately identify and isolate senescent immune cells are missing. By measuring senescence-associated ß-galactosidase activity, a hallmark of senescent cells, we demonstrate here that healthy humans develop senescent T lymphocytes in peripheral blood with advancing age. Particularly senescent CD8+ T cells increased in abundance with age, ranging from 30% of the total CD8+ T cell population in donors in their 20s and reaching levels of 64% in donors in their 60s. Senescent CD8+ T cell populations displayed features of telomere dysfunction-induced senescence as well as p16-mediated senescence, developed in various T cell differentiation states and established gene expression signatures consistent with the senescence state observed in other cell types. On the basis of our results we propose that cellular senescence of T lymphocytes is a major contributing factor to the observed decline of immune cell function with advancing age and that immune cell senescence, therefore, plays a significant role in the increased susceptibility of the elderly to age-associated diseases and infection.
Mutatorfoci are regulated by developmental stage, RNA, and the germline cell cycle inCaenorhabditis elegans
Authors: Uebel Celja J. , Agbede Dana , Wallis Dylan C. , Phillips Carolyn M. 
Published: June 2020

ABSTRACTRNA interference is a crucial gene regulatory mechanism inCaenorhabditis elegans. Phase-separated perinuclear germline compartments calledMutatorfoci are a key element of RNAi, ensuring robust gene silencing and transgenerational epigenetic inheritance. Despite their importance,Mutatorfoci regulation is not well understood, and observations ofMutatorfoci have been largely limited to adult hermaphrodite germlines. Here we reveal that punctateMutatorfoci arise in the progenitor germ cells of early embryos and persist throughout all larval stages. They are additionally present throughout the male germline and in the cytoplasm of post-meiotic spermatids, suggestive of a role in paternal epigenetic inheritance. In the adult germline, transcriptional inhibition results in a pachytene-specific loss ofMutatorfoci, indicating thatMutatorfoci are partially reliant on RNA for their stability. Finally, we demonstrate thatMutatorfoci intensity is modulated by the stage of the germline cell cycle and specifically, thatMutatorfoci are brightest and most robust in the mitotic cells, transition zone, and late pachytene of adult germlines. Thus, our data defines several new factors that modulateMutatorfoci morphology which may ultimately have implications for efficacy of RNAi in certain cell stages or environments.