bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed methods evaluation of the impact of the COVID-19 ICU remote-learning rehabilitation course for frontline health professionals during the COVID-19 pandemic in the UK
Authors: Corner Evelyn J , Zhang Xiaoxi , Van Willigen Zoe , Tatam Kate , Camilleri Matthew , Monkhouse Alex , Bear Danielle E , Hemsley Alex , Puthucheary Zudin , Rosenberg Alex , McRae Jackie , Harvey Alex , Ford Debbie , Firshman Penelope , Norris Meriel 
Published: September 2021

Background Optimising outcomes for critically ill patients with COVID-19 patients requires early interdisciplinary rehabilitation. As admission numbers soared through the pandemic, the redeployed workforce needed rapid, effective training to deliver these rehabilitation interventions. Methods The COVID-19 ICU Remote-Learning Rehab Course (CIRLC-rehab) is a one-day interdisciplinary course developed after the success of CIRLC-acute. The aim of CIRLC-rehab was to rapidly train healthcare professionals to deliver physical, nutritional and psychological rehabilitation strategies in the ICU/acute setting. The course used blended learning with interactive tutorials delivered by shielding critical care professionals. CIRLC-rehab was evaluated through a mixed-methods approach, including questionnaires, and follow-up semi-structured interviews to evaluate perceived impact on clinical practice. Quantitative data are reported as n (%) and means (SD). Inductive descriptive thematic analysis with methodological triangulation was used to analyse the qualitative data from the questionnaires and interviews. Results 805 candidates completed CIRLC-rehab. 627 (78.8%) completed the post-course questionnaire. 95% ( n = 596) found CIRLC-rehab extremely or very useful and 96.0% ( n = 602) said they were very likely to recommend the course to colleagues. Overall confidence rose from 2.78/5 to 4.14/5. The course promoted holistic and humanised care, facilitated informal networks, promoted interdisciplinary working and equipped the candidates with practical rehabilitation strategies that they implemented into clinical practice. Conclusion This pragmatic solution to educating redeployed staff during a pandemic increased candidates’ confidence in the rehabilitation of critically ill patients. There was also evidence of modifications to clinical care utilising learning from the course that subjectively facilitated holistic and humanised rehabilitation, combined with the importance of recognising the humanity, of those working in ICU settings themselves. Whilst these data are self-reported, we believe that this work demonstrates the real-term benefits of remote, scalable and rapid educational delivery.
Design of an international investigator-initiated study on MOdern Treatment of Inhibitor-positiVe pATiEnts with haemophilia A (MOTIVATE)
Authors: Escuriola Ettingshausen Carmen , Sidonio Robert F. 
Published: September 2021

Background: Inhibitor development is the most serious treatment-related complication of replacement coagulation factor VIII (FVIII) therapy for patients with haemophilia A. Immune tolerance induction (ITI), which involves intensive and prolonged treatment with plasma-derived or recombinant FVIII, is the only clinically proven strategy for eradication of inhibitors. The bispecific antibody emicizumab is approved for use in patients with and without inhibitors to prevent bleeding but does not eliminate inhibitors. MOTIVATE ( www.motivate-study.com ) aims to capture different approaches to the treatment and management of patients with haemophilia A and inhibitors, document current ITI approaches from real-world clinical experience, and evaluate the efficacy and safety of ITI, emicizumab prophylaxis and ITI with emicizumab prophylaxis. Methods: The investigator-initiated MOTIVATE study [ClinicalTrials.gov identifier: NCT04023019; EudraCT 2019-003427-38] will investigate in real-life clinical practice the management of patients with haemophilia A of any severity who have developed inhibitors to FVIII. All treatment is at the investigator’s discretion. The following treatment approaches will be evaluated: Group 1 – ITI with Nuwiq®, octanate® or wilate® and aPCC/rFVIIa if needed to treat bleeding episodes (BEs) or during surgery or for prophylaxis; Group 2 – ITI with Nuwiq®, octanate® or wilate® and emicizumab prophylaxis and aPCC/rFVIIa if needed to treat BEs or during surgery; Group 3 – routine prophylaxis with emicizumab, aPCC or rFVIIa without ITI and aPCC/rFVIIa if needed to treat BEs or during surgery. Patients will not be randomised to a treatment group and may change groups during the study. Conclusions: It is planned to enrol 120 patients who will be followed for up to 5 years. Optional sub-studies will explore factors that may influence ITI results as well as the impact of different treatment approaches on important aspects of patient health, including joint and bone health and the risk of thrombotic events.
Pathological analysis of periprosthetic soft tissue and modes of failure in revision total joint arthroplasty patients
Authors: Bettiol Patrick , Egan Alec , Cox Cameron , Wait Eric , Brindley George 
Published: September 2021

Objectives: Implant failure leading to revision total joint arthroplasty can occur through a variety of different mechanisms which are typically associated with a soft tissue response adjacent to the implant that provide insight into the underlying etiology of implant failure. The objective of this study was to elucidate mechanisms of implant failure as they relate to histological classification and findings of adjacent periprosthetic tissue. Methods: Histological analysis of soft tissue adjacent to the implant was performed in 99 patients with an average age of 64 years old and grouped into four categories based on the study conducted by Morawietz et al.: Type I (N = 47) Wear particle induced type Type II (N = 7) Infectious type Type III (N = 19) Combined type I and II Type IV (N = 26) Indeterminant type Modes of failure were categorized into five groupings based on the study conducted by Callies et al.: Instability (N = 35), Aseptic Loosening (N = 24), Hardware and/or Mechanical Failure (N = 15), Septic (N = 13), and Other failures (N = 12). We calculated odds ratios and conducted regression analysis to assess the relationship between modes of failure and histological findings as well as modes of failure and comorbidities. Results: Hardware/mechanical failure was independently correlated with histological findings of anucleate protein debris, histiocytes, Staphylococcus epidermidis, and synovitis. Furthermore, hardware/mechanical failure was independently correlated with osteosarcoma as a co-morbidity. Septic failure was associated with histological findings of Enterococcus, granulation tissue, and tissue necrosis as well as comorbidities of Crohn’s disease, deep venous thrombosis, lung disease, and rheumatoid arthritis. Infection was 5.8 times more likely to be associated with Type II histology. Aseptic loosening was associated with histologic findings of synovitis. Conclusion: Our findings support the existing literature on periprosthetic tissue analysis in revision total joint arthroplasty which may improve surgeon understanding of the patholophysiological mechanisms that contribute to implant failure and revision surgery.
Adductor Muscle Injuries in UEFA Soccer Athletes: A Matched-Cohort Analysis of Injury Rate, Return to Play, and Player Performance From 2000 to 2015
Authors: Lavoie-Gagne Ophelie , Mehta Nabil , Patel Sumit , Cohn Matthew R. , Forlenza Enrico , Nwachukwu Benedict U. , Forsythe Brian 
Published: September 2021

Background: The effects of adductor muscle injury on performance in soccer athletes are unknown. Purpose: To (1) determine the rate and time to return to play (RTP) after adductor muscle injury, (2) investigate the rate of reinjury after RTP, and (3) investigate any long-term effects of injury on elite soccer player performance. Study Design: Cohort study; Level of evidence, 3. Methods: Using publicly available records, athletes sustaining adductor muscle injury were identified across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2000 and 2015. Injured athletes were matched to controls by demographic characteristics and performance metrics from 1 season before the index timepoint. Investigations included the rate of RTP, reinjuries, player characteristics associated with RTP within 2 seasons, player availability, field time, and performance metrics during the 4 seasons after injury. Results: A total of 671 players with adductor muscle injury were included. Based on time to RTP, 86% of injuries were mild to moderate (4-28 days missed), and 4% required surgical intervention. Players with adductor muscle injury were absent for a median of 22 days (range, 1-700 days) and 4 games (range, 1-76 games). A total of 521 (78%) players returned at the same level, with no demographic or clinical characteristics associated with RTP on the multivariable regression. Of those returning to play, 143 (21%) experienced adductor reinjury. After RTP, defenders demonstrated decreased field time compared with controls ( P < .05). As compared with controls, defenders and midfielders scored more points and goals per game during the season of the injury ( P < .01), while attackers recorded more goals and assists per game the season after injury ( P < .05). Conclusion: Only 3 in 4 players (78%) returned to participate in an official match, and the reinjury rate was high (21%). After RTP, defenders demonstrated decreased field time versus controls. On the other hand, defenders and midfielders recorded more points and goals per game, while attackers recorded more goals and assists per game versus controls. Although the multivariable analysis results did not identify player characteristics associated with RTP, there was a position-dependent association on player performance after RTP.
JMML tumor cells disrupt normal hematopoietic stem cells by imposing inflammatory stress through overproduction of IL-1β
Authors: Yan Yuhan , Dong Lei , Chen Chao , Bunting Kevin D. , Li Qianjin , Stieglitz Elliot , Loh Mignon L. , Qu Cheng-Kui 
Published: September 2021

AbstractDevelopment of normal blood cells is often suppressed in juvenile myelomonocytic leukemia (JMML), a myeloproliferative neoplasm (MPN) of childhood, causing complications and impacting therapeutic outcomes. However, the mechanism underlying this phenomenon remains uncharacterized. To address this question, we induced the most common mutation identified in JMML (Ptpn11E76K) specifically in the myeloid lineage with hematopoietic stem cells (HSCs) spared. These mice uniformly developed a JMML-like MPN. Importantly, HSCs in the same bone marrow (BM) microenvironment were aberrantly activated and differentiated at the expense of self-renewal. As a result, HSCs lost quiescence and became exhausted. A similar result was observed in wild-type (WT) donor HSCs when co-transplanted with Ptpn11E76K/+ BM cells into WT mice. Co-culture testing demonstrated that JMML/MPN cells robustly accelerated differentiation in mouse and human normal hematopoietic stem/progenitor cells. Cytokine profiling revealed that Ptpn11E76K/+ MPN cells produced excessive IL-1β, but not IL-6, T NF-α, IFN-γ, IL-1α, or other inflammatory cytokines. Depletion of the IL-1β receptor effectively restored HSC quiescence, normalized their pool size, and rescued them from exhaustion in Ptpn11E76K/+/IL-1R−/− double mutant mice. These findings suggest IL-1β signaling as a potential therapeutic target for preserving normal hematopoietic development in JMML.
Overexpression of GINS4 is associated with poor prognosis and survival in glioma patients
Authors: Liu Binfeng , Liu Zhendong , Wang Yanbiao , Lian Xiaoyu , Han Zhibin , Cheng Xingbo , Zhu Yongjie , Liu Runze , Zhao Yaoye , Gao Yanzheng 
Published: September 2021

Abstract
Background
GINS4, an indispensable component of the GINS complex, is vital for a variety of cancer. However, no known empirical research has focused on exploring relationships between GINS4 and glioma. Thus, this study aims to understand and explain the role of GINS4 in glioma.

Method
First, we used the data in the CGGA, TCGA, GEO, GEPIA, and HPA databases to explore the expression level of GINS4 in glioma, the correlation between GINS4 expression and the clinical features of glioma, its impact on the survival of glioma patients, and verified the analysis results through RT-qPCR, IHC, and meta-analysis. Subsequently, GSEA enrichment analysis is used to find the potential molecular mechanism of GINS4 to promote the malignant process of glioma and the anti-glioma drugs that may target GINS4 screened by CMap analysis. Moreover, we further explored the influence of the GINS4 expression on the immune microenvironment of glioma patients through the TIMER database.

Results
Our results suggested that GINS4 was elevated in glioma, and the overexpression of GINS4 was connected with a vast number of clinical features. The next, GINS4 as an independent prognostic factor, which can result in an unfavorable prognosis of glioma. Once more, GINS4 may be participating in the oncogenesis of glioma through JAK-STAT signaling pathways, etc. 6-thioguanine, Doxazosin, and Emetine had potential value in the clinical application of drugs targeting GINS4. Finally, the expression exhibited a close relationship with some immune cells, especially Dendritic cells.

Conclusion
GINS4 is an independent prognostic factor that led to a poor prognosis of glioma. The present study revealed the probable underlying molecular mechanisms of GINS4 in glioma and provided a potential target for improving the prognosis of glioma.
Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia
Authors: Alper Judy , Seifert Alan C. , Verma Gaurav , Huang Kuang-Han , Jacob Yael , Al Qadi Ameen , Rutland John W. , Patel Sheetal , Bederson Joshua , Shrivastava Raj K. , Delman Bradley N. , Balchandani Priti 
Published: September 2021

Abstract
Background
Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls.

Methods
Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls.

Results
CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed.

Conclusions
These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.
Effects of sensory distraction and salience priming on emotion identification in autism: an fMRI study
Authors: Patterson Genevieve , Cummings Kaitlin K. , Jung Jiwon , Okada Nana J. , Tottenham Nim , Bookheimer Susan Y. , Dapretto Mirella , Green Shulamite A. 
Published: September 2021

Abstract
Background
Social interaction often occurs in noisy environments with many extraneous sensory stimuli. This is especially relevant for youth with autism spectrum disorders (ASD) who commonly experience sensory over-responsivity (SOR) in addition to social challenges. However, the relationship between SOR and social difficulties is still poorly understood and thus rarely addressed in interventions. This study investigated the effect of auditory sensory distracters on neural processing of emotion identification in youth with ASD and the effects of increasing attention to social cues by priming participants with their own emotional faces.

Methods
While undergoing functional magnetic resonance imaging (fMRI), 30 youth with ASD and 24 typically developing (TD) age-matched controls (ages 8–17 years) identified faces as happy or angry with and without simultaneously hearing aversive environmental noises. Halfway through the task, participants also viewed videos of their own emotional faces. The relationship between parent-rated auditory SOR and brain responses during the task was also examined.

Results
Despite showing comparable behavioral performance on the task, ASD and TD youth demonstrated distinct patterns of neural activity. Compared to TD, ASD youth showed greater increases in amygdala, insula, and primary sensory regions when identifying emotions with noises compared to no sounds. After viewing videos of their own emotion faces, ASD youth showed greater increases in medial prefrontal cortex activation compared to TD youth. Within ASD youth, lower SOR was associated with reduced increased activity in subcortical regions after the prime and greater increased activity in the ventromedial prefrontal cortex after the prime, particularly in trials with noises.

Conclusions
The results suggest that the sensory environment plays an important role in how ASD youth process social information. Additionally, we demonstrated that increasing attention to relevant social cues helps ASD youth engage frontal regions involved in higher-order social cognition, a mechanism that could be targeted in interventions. Importantly, the effect of the intervention may depend on individual differences in SOR, supporting the importance of pre-screening youth for sensory challenges prior to social interventions.
Factors influencing protective behavior in the post-COVID-19 period in China: a cross-sectional study
Authors: Shi Guiqian , Zhong Xiaoni , He Wei , Liu Hui , Liu Xiaoyan , Ma Mingzhu 
Published: September 2021

AbstractBackgroundThe study aimed to explore the factors influencing protective behavior and its association with factors during the post-COVID-19 period in China based on the risk perception emotion model and the protective action decision model (PADM).MethodsA total of 2830 valid questionnaires were collected as data for empirical analysis via network sampling in China. Structural equation modeling (SEM) was performed to explore the relationships between the latent variables.ResultsSEM indicated that social emotion significantly positively affected protective behavior and intention. Protective behavioral intention had significant direct effects on protective behavior, and the direct effects were also the largest. Government trust did not have a significant effect on protective behavior but did have a significant indirect effect. Moreover, it was found that government trust had the greatest direct effect on social emotion. In addition, we found that excessive risk perception level may directly reduce people’s intention and frequency of engaging in protective behavior, which was not conducive to positive, protective behavior.ConclusionIn the post-COVID-19 period, theoretical framework constructed in this study can be used to evaluate people’s protective behavior. The government should strengthen its information-sharing and interaction with the public, enhance people’s trust in the government, create a positive social mood, appropriately regulate people's risk perception, and, finally, maintain a positive attitude and intent of protection.
A DNA barcode library for mangrove gastropods and crabs of Hong Kong and the Greater Bay Area reveals an unexpected faunal diversity associated with the intertidal forests of Southern China
Authors: Bravo Henrique , Cheng Christine L. Y. , Iannucci Alessio , Natali Chiara , Quadros Aline , Rhodes Martin , Yip Matthew M. L. , Cannicci Stefano , Fratini Sara 
Published: September 2021

AbstractBackgroundMangroves are tropical and subtropical intertidal forests colonising sheltered coasts across the world. They host a unique faunal community, dominated by brachyuran crabs and gastropods. These invertebrates strongly contribute to the functionality of the entire forest. The reliable assessment of mangrove faunal diversity is, thus, a crucial step for efficient management and conservation plans, but it is hindered by difficulties in species identification. Here we provide a verified DNA barcode library for brachyuran crabs and gastropods inhabiting the mangroves of the Greater Bay Area, Southern China. In particular, we collected and morphologically identified 1100 specimens of mangrove associated brachyuran crabs and gastropods. The partial sequences of the mtDNA cytochrome oxidase subunit I gene were obtained from 275 specimens. Barcode sequences were then used to delineate Molecular Operational Taxonomic Units (MOTUs), employing three different delimitation methods: the automatic barcode gap discovery (ABGD) method, the general mixed Yule coalescent (GMYC) model and a Bayesian implementation of the Poisson tree processes (bPTP) model.ResultsBy integrating DNA barcodes with morphology, we identified 44 gastropod species and 58 brachyuran species associated with Hong Kong mangroves, with five and seven new records, for gastropods and crabs, respectively, for the Greater Bay Area. The delineation of MOTUs based on barcode sequences revealed a strong congruence between morphological and molecular identification for both taxa, showing the high reliability of the barcode library.ConclusionsThis study provides the first reference barcode library for mangrove-associated macrobenthic fauna in the Greater Bay Area and represents a reliable tool to management and conservation plans. Our molecular analyses resolved long lasting taxonomic misidentifications and inconsistencies and updated the knowledge on the geographical distribution of Asian mangrove associated fauna, ultimately highlighting a level of biodiversity higher than previously thought for Southern China.