bluuebunny/crossref_metadata_2025_split huggingface dataset:
The coordinated replication of Vibrio cholerae’s two chromosomes required the acquisition of a unique domain by the RctB initiator
Authors: Fournes Florian , Niault Theophile , Czarnecki Jakub , Tissier-Visconti Alvise , Mazel Didier , Val Marie-Eve 
Published: September 2021

Abstract
Vibrio cholerae, the pathogenic bacterium that causes cholera, has two chromosomes (Chr1, Chr2) that replicate in a well-orchestrated sequence. Chr2 initiation is triggered only after the replication of the crtS site on Chr1. The initiator of Chr2 replication, RctB, displays activities corresponding with its different binding sites: initiator at the iteron sites, repressor at the 39m sites, and trigger at the crtS site. The mechanism by which RctB relays the signal to initiate Chr2 replication from crtS is not well-understood. In this study, we provide new insights into how Chr2 replication initiation is regulated by crtS via RctB. We show that crtS (on Chr1) acts as an anti-inhibitory site by preventing 39m sites (on Chr2) from repressing initiation. The competition between these two sites for RctB binding is explained by the fact that RctB interacts with crtS and 39m via the same DNA-binding surface. We further show that the extreme C-terminal tail of RctB, essential for RctB self-interaction, is crucial for the control exerted by crtS. This subregion of RctB is conserved in all Vibrio, but absent in other Rep-like initiators. Hence, the coordinated replication of both chromosomes likely results from the acquisition of this unique domain by RctB.
Structural basis of chromatin regulation by histone variant H2A.Z
Authors: Lewis Tyler S , Sokolova Vladyslava , Jung Harry , Ng Honkit , Tan Dongyan 
Published: September 2021

Abstract
The importance of histone variant H2A.Z in transcription regulation has been well established, yet its mechanism-of-action remains enigmatic. Conflicting evidence exists in support of both an activating and a repressive role of H2A.Z in transcription. Here we report cryo-electron microscopy (cryo-EM) structures of nucleosomes and chromatin fibers containing H2A.Z and those containing canonical H2A. The structures show that H2A.Z incorporation results in substantial structural changes in both nucleosome and chromatin fiber. While H2A.Z increases the mobility of DNA terminus in nucleosomes, it simultaneously enables nucleosome arrays to form a more regular and condensed chromatin fiber. We also demonstrated that H2A.Z’s ability to enhance nucleosomal DNA mobility is largely attributed to its characteristic shorter C-terminus. Our study provides the structural basis for H2A.Z-mediated chromatin regulation, showing that the increase flexibility of the DNA termini in H2A.Z nucleosomes is central to its dual-functions in chromatin regulation and in transcription.
Acute paediatric kidney replacement therapies in Europe: demographic results from the EurAKId Registry
Authors: Guzzo Isabella , de Galasso Lara , Bayazit Aysun Karabay , Yildizdas Dincer , Schmitt Claus Peter , Hayes Wesley , Shroff Rukshana , Jankauskiene Augustina , Virsilas Ernestas , Longo Germana , Vidal Enrico , Mir Sevgi , Bulut Ipek Kaplan , Tkaczyk Marcin , Mencarelli Francesca , Bertulli Cristina , Cvetkovic Mrjana , Kostic Mirjana , Paglialonga Fabio , Montini Giovanni , Yilmaz Ebru , Teixeira Ana , Atmis Bahriye , Schaefer Franz 
Published: September 2021

ABSTRACTBackgroundAcute kidney injury (AKI), particularly that requiring dialysis, is a severe complication in hospitalized children that is associated with high morbidity and mortality. A prospective European AKI registry (EurAKId registry, NCT02960867) was created to describe the epidemiology and outcomes of paediatric patients treated with acute dialysis.MethodsChildren were recruited who were between 0 and 18 years of age and were treated both in and outside the paediatric intensive care unit (PICU) with peritoneal dialysis (PD), haemodialysis (HD) or continuous kidney replacement therapy (CKRT) for AKI or metabolic derangement, fluid overload (FO), sepsis or respiratory distress. Five age groups and 12 categories of primary diseases were defined.ResultsData on 340 patients were analysed, of whom 86% received dialysis for AKI and 14% for reasons other than AKI. Boys accounted for 60% of the patients. Illness severity was greater in children with cardiac and haematologic diseases than those with kidney diseases. Most patients received dialysis in the PICU (84%). The most frequently used dialysis modality was CKRT (64%), followed by PD (14%) and HD (14%). The overall survival rate was 65%. Survival was significantly lower in children with three comorbidities than in children with no comorbidities (41% and 83%; P &lt; 0.001).ConclusionsThe EurAKId registry is the first prospective registry considering paediatric acute kidney replacement therapies (KRTs) in both critical and non-critical care settings, focusing on the three dialysis modalities in Europe. The clinical indications for KRT have expanded; our population was characterized by critically ill patients, primarily boys, who frequently received dialysis in the PICU with CKRT.
The impact of depression, anxiety and comorbidity on occupational outcomes
Authors: Deady M , Collins D A J , Johnston D A , Glozier N , Calvo R A , Christensen H , Harvey S B 
Published: September 2021

Abstract

Background
Anxiety and depression account for considerable cost to organizations, driven by both presenteeism (reduced performance due to attending work while ill) and absenteeism. Most research has focused on the impact of depression, with less attention given to anxiety and comorbid presentations.

Aims
To explore the cross-sectional relationship between depression and anxiety (individually and comorbidly) on workplace performance and sickness absence.

Methods
As part of a larger study to evaluate a mental health app, 4953 working Australians were recruited. Participants completed in-app assessment including demographic questions, the Patient Health Questionnaire-9, two-item Generalized Anxiety Disorder and questions from the World Health Organization Health and Work Performance Questionnaire. Cut-off scores were used to establish probable cases of depression alone, anxiety alone and comorbidity.

Results
Of the total sample, 7% met cut-off for depression only, 13% anxiety only, while 16% were comorbid. Those with comorbidity reported greater symptom severity, poorer work performance and more sickness absence compared to all other groups. Presenteeism and absenteeism were significantly worse in those with depression only and anxiety only compared to those with non-clinical symptom levels. Although those with depression alone tended to have poorer outcomes than the anxiety-only group, when sample prevalence rates were considered, the impact on presenteeism was comparable.

Conclusions
Workplace functioning is heavily impacted by depression and anxiety both independently and where they co-occur. While comorbidity and more severe depression presentations stand out as impairing, workplace interventions should also prioritize targeting of anxiety disorders (and associated presenteeism) given their high population prevalence.
A kinetics of the spinning gravitational field
Authors: Yamamoto Tokonatsu 
Published: September 2021

Abstract
According to the general theory of relativity, a spinning shell drags its gravitational field. Owing to this frame-dragging effect, the gravitational field rotates. The spinning field also drags particles in the field. Although this moment of force is negligibly small, its kinetics should be properly handled. In this study, we show that the spinning gravitational field generates a central force, which makes the spinning shells heavy. The observed galactic rotation is naturally described by this central force without dark matter. We describe the kinetics of the spinning field and central force.
Incidence and prevalence of juvenile idiopathic arthritis in the United Kingdom, 2000–2018: results from the Clinical Practice Research Datalink
Authors: Costello Ruth , McDonagh Janet , Hyrich Kimme L , Humphreys Jenny H 
Published: September 2021

AbstractObjectiveThe incidence and prevalence of JIA was last estimated in the UK in 1994. Since then the disease has been reclassified, the specialty of paediatric rheumatology has evolved and there has been a significant shift in disease management with new advanced therapies. This study aimed to provide up-to-date national estimates of this disease.MethodsChildren and young people (CYP) with JIA were identified in the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, which source data from the two most commonly used primary care electronic health record systems in the UK. These databases were combined and the cohort was identified (2000–18) using predefined code lists. Validation was performed through linkage to the England Hospital Episode Statistics. Annual incidence and prevalence rates were calculated and stratified by gender, age group and nation of the UK. Direct standardization to the UK population was performed and 5 year incidence rates were calculated between 2003 and 2018.ResultsThe age-standardized incidence rate was 5.61 per 100 000 population. The age-standardized prevalence rate in 2018 was 43.5 per 100 000. Rates were higher in Scotland compared with England: incidence rate ratio 1.27 (95% CI 1.11, 1.46). The 5 year incidence rates did not change significantly over time.ConclusionsThis study has provided the first contemporaneous estimates of occurrence of JIA in the UK in 25 years. These data provide important estimates to inform resource allocation and health service development for management of JIA.
The Strait of Gibraltar is an ineffective palaeogeographic barrier for some flightless darkling beetles (Coleoptera: Tenebrionidae:Pimelia)
Authors: Mas-Peinado Paloma , García-París Mario , Ruiz José L , Buckley David 
Published: September 2021

AbstractThe geographic distribution of a species is shaped by its biology and by environmental and palaeogeographic factors that interact at different spatial-temporal scales, which leads to distributions and diversification patterns observed between and within lineages. The darkling beetle genus Pimelia has been diversifying for more than 31.2 Mya showing different colonization patterns after the opening of the Gibraltar Strait 5 Mya. Three of the 14 subgenera of Pimelia have populations on both sides of the Strait. Through extensive sampling and the analysis of three molecular markers, we determine levels of intra- and interspecific genetic variation, identify evolutionary lineages in subgenera, estimate their temporal origin and distribution ranges and discuss the historical basis for the geographic and diversification patterns of Pimelia around the Strait. This single geographical feature acted both as a barrier and as a dispersal route for different Pimelia species. The Strait has represented a strong barrier for the subgenus Magrebmelia since the Middle Miocene. However, the subgenera Amblyptera and Amblypteraca share repetitive signatures of post-Messinian colonization across the Strait, possibly driven by stochastic or ‘catastrophic’ events such as tsunamis. Our demographic analyses support Wallace’s hypothesis on insect dispersal stochasticity. Some taxonomic changes, including the designation of a lectotype for Pimelia maura, are also proposed.
Preventing Medjacking
Authors: Cuningkin Veneine , Riley Elizabeth , Rainey Larronda 
Published: September 2021

ABSTRACT:
Advances in medical device technology have led to greater connectivity with other devices, networks, and systems, raising concerns about associated security risks. Many clinicians, as well as the patients who rely on these lifesaving devices, are unaware of these risks and how they can be mitigated. This article describes several types of cyberattacks, including medjacking, hacking, and ransomware, and what nurses can do to guard against security threats and educate patients.
A Mixed-Methods Study of Teaching Health Center Residents’ Experiences of Mentorship, Career Planning, and Postresidency Practice Environments
Authors: Strasser Julia H. , Jewers Mariellen M. , Kepley Hayden , Chen Candice , Erikson Clese , Regenstein Marsha 
Published: September 2021

Purpose
The Teaching Health Center (THC) Graduate Medical Education program enables primary care physicians to train in community-based, underserved settings by shifting the payment structure and training environment for graduate medical education. To understand how THCs have successfully trained primary care physicians who practice in community-based settings, the authors conducted a mixed-methods exploratory study to examine THC residency graduates’ experiences of mentorship and career planning during their residencies, perceptions of preparation for postresidency practice, and how these experiences were related to postresidency practice environments.

Method
Surveys were conducted for all 804 graduating THC residents nationally, 2014–2017 (533 respondents, 66% response rate). Three quantitative outcomes were measured: graduates’ perceptions of preparation for practice after residency (Likert scale), satisfaction with mentorship and career planning (Likert scale), and characteristics of postresidency practice environment (open-ended). A qualitative analysis of open-text survey answers, using thematic content analysis, was also conducted.

Results
Most THC graduates (68%) were satisfied with their mentorship and career planning experience and generally felt prepared for postresidency practice in multiple settings (78%–93%). Of the 533 THC graduates who provided information about their practice environment, 445 (84%) were practicing in primary care; nationally, 64% of physicians who completed primary care residencies practiced in primary care. Of the 445 THC graduates practicing in primary care, 12% practiced in rural areas, compared with 7% of all physicians. Just over half of THC graduates (51%) practiced in medically underserved areas, compared with 39% of all physicians.

Conclusions
This study offers early evidence that the THC model produces and retains primary care physicians who are well prepared to practice in underserved areas. Given these promising findings, there appears to be a substantial benefit to growing the THC program. However, the program continues to face uncertainty around ongoing, stable funding.
Simulating for Quality: A Centralized Quality Improvement and Patient Safety Simulation Curriculum for Residents and Fellows
Authors: Luty Jacob T. , Oldham Hayden , Smeraglio Andrea , DiVeronica Matthew , Terndrup Christopher , Tibayan Frederick A. , Engle Joshua , Lepin Kimberly , Nonas Stephanie 
Published: September 2021

Problem
Requirements for experiential education in quality improvement and patient safety (QI/PS) in graduate medical education (GME) have recently expanded. Major challenges to meeting these requirements include a lack of faculty with the needed expertise, paucity of standardized curricular models allowing for skill demonstration, and inconsistent access to data for iterative improvement.

Approach
In October 2017, the authors began development of a centralized QI/PS flipped-classroom simulation-based medical education (SBME) curriculum for GME trainees across multiple disciplines at Oregon Health & Science University (OHSU). The curriculum development team included OHSU and Veterans Affairs faculty with experience in QI/PS and SBME, as well as house officers. The curriculum consisted of a preassessment and prework readings and videos (sent 3 weeks before the simulation day) and an 8-hour simulation day, with introductory activities, 4 linked simulation sessions, and concluding activities. The 4 linked sessions followed the same medication error from disclosure and reporting to root cause analysis, iterative implementation of an action plan, and consolidation of lessons learned into routine operations with Lean huddles.

Outcomes
In academic year 2018–2019, 71 residents and fellows of various postgraduate years from 23 training programs enrolled in 2 pilot sessions. Learners reacted favorably to the simulation curriculum. Learner attitudes, confidence, knowledge, and skills significantly increased across all QI/PS domains studied.

Next Steps
This approach focuses a small cadre of educators toward the creation of a centralized resource that, owing to its experiential SBME foundation, can accommodate many learners with data-driven practice-based learning and improvement cycles in a shorter time frame than traditional QI initiatives. Next steps include the addition of a control group, assessment of the sustainability of learner outcomes, translation of learning to behavior change and improvements in patient and health system outcomes, and adapting the materials to include learners from different professions and levels.
Cerebral arterial fenestration associated with stroke and other cerebrovascular diseases
Authors: Ye Dan , Huang Jinzhong , Wang Sulei , Sheng Shiying , Liu Meng 
Published: September 2021

Background
Cerebral arterial fenestration is a rare vascular malformation that has not been fully understood. Whether it is related to cerebrovascular diseases remains to be determined. In this study, we aimed to investigate the imaging characteristics of cerebral fenestrations, the clinical characteristics of fenestrations complicated with cerebrovascular diseases, and the correlation between fenestrations and cerebrovascular diseases.

Methods
We reviewed the magnetic resonance imaging and computed tomography (CT) imaging findings of patients with cerebrovascular fenestrations in the Third Affiliated Hospital of Soochow University from January 2016 to December 2020, mainly focused on the shape and location of fenestrations. According to the location of fenestrated arteries, patients were divided into the internal carotid arterial system (ICAS) group and the vertebrobasilar arterial system (VAS) group. For patients complicated with cerebrovascular diseases, detailed data about the demographics and clinical characteristics were recorded. Stroke patients with injured lesions located in the territories of fenestrated arteries were further screened out and analyzed. Moreover, the proportions of cerebrovascular diseases including stroke between the ICAS group and the VAS group were compared.

Results
A total of 280 cerebrovascular fenestrations were found in 274 patients (six patients had two fenestrations). The most frequently involved vessels were the anterior cerebral artery (123/280), the basilar artery (76/280) and the vertebral artery (35/280). As to the shape of fenestrations, slit-like fenestrations accounted for 63.2% (177/280), followed by convex-lens-like type 26.1% (73/280) and duplicated type 10.7% (30/280). A total of 70 patients were complicated with cerebrovascular diseases, including ischemic stroke 64.3% (45/70), hemorrhagic stroke 22.9% (16/70), aneurysm 10% (7/70), arteriovenous malformation 1.4% (1/70) and cavernous hemangioma 1.4% (1/70). There were no significant differences between the ICAS group and the VAS group in terms of the demographics and clinical characteristics. Furthermore, among the 61 patients complicated with stroke, 16 patients’ stroke lesions were located in the territories of fenestrated arteries, including 12.5% (2/16) in the ICAS and 87.5% (14/16) in the VAS. In addition, compared with the ICAS group, the proportions of cerebrovascular diseases including stroke in patients with fenestrations were higher in the VAS group (P < 0.05).

Conclusions
Cerebral arterial fenestrations are most commonly found in the anterior cerebral artery, the basilar artery and the vertebral artery. Vertebrobasilar fenestrations are more related to cerebrovascular diseases, especially stroke.
Ethanol and opioids do not act synergistically to depress excitation in carotid body type I cells
Authors: Rakoczy Ryan , Kamra Kajal , Yi Yoon-Jae , Wyatt Christopher 
Published: September 2021

Objective
The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation.

Methods
Carotid bodies were removed from 56 Sprague–Dawley rats (1021 days old) and then enzymatically dissociated to allow calcium imaging of isolated chemosensitive type I cells. Cells were stimulated with high K+ in the presence and absence of the µ-opioid agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (10 µM), a maximal sublethal concentration of ethanol (3 g L-1, 65.1 mM) or a combination of both.

Results
DAMGO alone significantly inhibited Ca2+ influx but this effect was not potentiated by the high concentration of ethanol.

Conclusion
These results indicate for the first time that while opioids may suppress breathing via an action at the level of the carotid bodies, ethanol is unlikely to potentiate inhibition via this pathway. Thus, the synergistic effects of ethanol and opioids on ventilatory parameters are likely mediated by central rather than peripheral actions.