bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate transcriptome analysis identifies networks and key drivers of chronic lymphocytic leukemia relapse risk and patient survival
Authors: Griffen Ti’ara L. , Dammer Eric B. , Dill Courtney D. , Carey Kaylin M. , Young Corey D. , Nunez Sha’Kayla K. , Ohandjo Adaugo Q. , Kornblau Steven M. , Lillard James W. 
Published: June 2021

AbstractBackgroundChronic lymphocytic leukemia (CLL) is an indolent heme malignancy characterized by the accumulation of CD5+CD19+B cells and episodes of relapse. The biological signaling that influence episodes of relapse in CLL are not fully described. Here, we identify gene networks associated with CLL relapse and survival risk.MethodsNetworks were investigated by using a novel weighted gene network co-expression analysis method and examining overrepresentation of upstream regulators and signaling pathways within co-expressed transcriptome modules across clinically annotated transcriptomes from CLL patients (N = 203). Gene Ontology analysis was used to identify biological functions overrepresented in each module. Differential Expression of modules and individual genes was assessed using an ANOVA (Binet Stage A and B relapsed patients) or T-test (SF3B1 mutations). The clinical relevance of biomarker candidates was evaluated using log-rank Kaplan Meier (survival and relapse interval) and ROC tests.ResultsEight distinct modules (M2, M3, M4, M7, M9, M10, M11, M13) were significantly correlated with relapse and differentially expressed between relapsed and non-relapsed Binet Stage A CLL patients. The biological functions of modules positively correlated with relapse were carbohydrate and mRNA metabolism, whereas negatively correlated modules to relapse were protein translation associated. Additionally, M1, M3, M7, and M13 modules negatively correlated with overall survival. CLL biomarkers BTK, BCL2, and TP53 were co-expressed, while unmutated IGHV biomarker ZAP70 and cell survival-associated NOTCH1 were co-expressed in modules positively correlated with relapse and negatively correlated with survival days.ConclusionsThis study provides novel insights into CLL relapse biology and pathways associated with known and novel biomarkers for relapse and overall survival. The modules associated with relapse and overall survival represented both known and novel pathways associated with CLL pathogenesis and can be a resource for the CLL research community. The hub genes of these modules, e.g., ARHGAP27P2, C1S, CASC2, CLEC3B, CRY1, CXCR5, FUT5, MID1IP1, and URAHP, can be studied further as new therapeutic targets or clinical markers to predict CLL patient outcomes.
Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts
Authors: Muro Shigeo , Sugiura Hisatoshi , Darken Patrick , Dorinsky Paul 
Published: June 2021

Abstract
Background
In the Phase III KRONOS study, triple therapy with budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) was shown to reduce exacerbations and improve lung function versus glycopyrronium/formoterol fumarate dihydrate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). However, whether the benefits related to the ICS component of BGF are driven by patients with high blood eosinophil counts (EOS) and/or airway reversibility has not been previously studied.

Methods
KRONOS was a Phase III, double-blind, parallel-group, multicenter, randomized, controlled study of patients with moderate-to-very-severe COPD. Patients were randomized 2:2:1:1 to receive BGF 320/14.4/10 μg, GFF 14.4/10 μg, budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg via a single Aerosphere inhaler, or open-label budesonide/formoterol fumarate dihydrate dry powder inhaler 400/12 μg (BUD/FORM DPI; Symbicort Turbuhaler) twice-daily for 24 weeks. Efficacy outcomes included in this post-hoc analysis were change from baseline in morning pre-dose trough FEV1 over weeks 12–24 and the rate of moderate-to-severe and severe COPD exacerbations. Adverse events in the non-reversible subgroup are also reported.

Results
Of 1896 patients analyzed, 948 (50%) were non-reversible and had EOS < 300 cells/mm3. In this group, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM (least squares mean treatment difference, 95% confidence interval [CI] 69 mL [39, 99], unadjusted p < 0.0001 and 51 mL [20, 81], unadjusted p = 0.0011, respectively) and was comparable to GFF. BGF also significantly reduced annual moderate-to-severe exacerbation rates versus GFF (rate ratio [95% CI] 0.53 [0.37, 0.76], unadjusted p = 0.0005), with numerical reductions observed versus BFF and BUD/FORM. These results were similar for the overall study population. Safety findings were generally similar between non-reversible patients with EOS < 300 cells/mm3 and the overall population.

Conclusions
In patients with moderate-to-very-severe COPD without airway reversibility and EOS < 300 cells/mm3, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM and significantly reduced the rate of moderate-to-severe exacerbations versus GFF. These findings demonstrate that BGF can provide benefits for a broad range of patients with COPD, and that the overall findings of the KRONOS primary analysis were not driven by patients with reversible airflow obstruction or high eosinophil counts.
Trial registration ClinicalTrials.gov, NCT02497001. Registered 14 July 2015, https://clinicaltrials.gov/ct2/show/NCT02497001
Effects of air pollution exposure on social behavior: a synthesis and call for research
Authors: Weitekamp Chelsea A. , Hofmann Hans A. 
Published: June 2021

Abstract
Background
There is a growing literature from both epidemiologic and experimental animal studies suggesting that exposure to air pollution can lead to neurodevelopmental and neuropsychiatric disorders. Here, we suggest that effects of air pollutant exposure on the brain may be even broader, with the potential to affect social decision-making in general.

Methods
We discuss how the neurobiological substrates of social behavior are vulnerable to air pollution, then briefly present studies that examine the effects of air pollutant exposure on social behavior-related outcomes.

Results
Few experimental studies have investigated the effects of air pollution on social behavior and those that have focus on standard laboratory tests in rodent model systems. Nonetheless, there is sufficient evidence to support a critical need for more research.

Conclusion
For future research, we suggest a comparative approach that utilizes diverse model systems to probe the effects of air pollution on a wider range of social behaviors, brain regions, and neurochemical pathways.
Risk and space: modelling the accessibility of stroke centers using day- & nighttime population distribution and different transportation scenarios
Authors: Rauch S. , Taubenböck H. , Knopp C. , Rauh J. 
Published: June 2021

Abstract
Purpose
Rapid accessibility of (intensive) medical care can make the difference between life and death. Initial care in case of strokes is highly dependent on the location of the patient and the traffic situation for supply vehicles. In this methodologically oriented paper we want to determine the inequivalence of the risks in this respect.

Methods
Using GIS we calculate the driving time between Stroke Units in the district of Münster, Germany for the population distribution at day- & nighttime. Eight different speed scenarios are considered. In order to gain the highest possible spatial resolution, we disaggregate reported population counts from administrative units with respect to a variety of factors onto building level.

Results
The overall accessibility of urban areas is better than in less urban districts using the base scenario. In that scenario 6.5% of the population at daytime and 6.8% at nighttime cannot be reached within a 30-min limit for the first care. Assuming a worse traffic situation, which is realistic at daytime, 18.1% of the population fail the proposed limit.

Conclusions
In general, we reveal inequivalence of the risks in case of a stroke depending on locations and times of the day. The ability to drive at high average speeds is a crucial factor in emergency care. Further important factors are the different population distribution at day and night and the locations of health care facilities. With the increasing centralization of hospital locations, rural residents in particular will face a worse accessibility situation.
Oncologic and long-term outcomes of enhanced recovery after surgery in cancer surgeries — a systematic review
Authors: Pang Qianyun , Duan Liping , Jiang Yan , Liu Hongliang 
Published: June 2021

Abstract
Background
Clinical evidence has proved that enhanced recovery after surgery (ERAS) can improve short-term clinical outcomes after various types of surgeries, but the long-term benefits have not yet been examined, especially with respect to cancer surgeries. Therefore, a systematic review of the current evidence was conducted.

Methods
The Pubmed, Cochrane Library, Embase, and Web of Science databases were searched using the following key words as search terms: “ERAS” or “enhanced recovery” or “fast track”, “oncologic outcome”, “recurrence”, “metastasis”, “long-term outcomes”, “survival”, and “cancer surgery”. The articles were screened using the inclusion and exclusion criteria, and the data from the included studies were extracted and analyzed.

Results
A total of twenty-six articles were included in this review. Eighteen articles compared ERAS and conventional care, of which, 12 studies reported long-term overall survival (OS), and only 4 found the improvement by ERAS. Four studies reported disease-free survival (DFS), and only 1 found the improvement by ERAS. Five studies reported the outcomes of return to intended oncologic treatment after surgery (RIOT), and 4 found improvements in the ERAS group. Seven studies compared high adherence to ERAS with low adherence, of which, 6 reported the long-term OS, and 3 showed improvements by high adherence. One study reported high adherence could reduce the interval from surgery to RIOT. Four studies reported the effect of altering one single item within the ERAS protocol, but the results of 2 studies were controversial regarding the long-term OS between laparoscopic and open surgery, and 1 study showed improvements in OS with restrictive fluid therapy.

Conclusions
The use of ERAS in cancer surgeries can improve the on-time initiation and completion of adjuvant chemotherapy after surgery, and the high adherence to ERAS can lead to better outcomes than low adherence. Based on the current evidence, it is difficult to determine whether the ERAS protocol is associated with long-term overall survival or cancer-specific survival.
Comparison of anticoagulated versus non-anticoagulated patients with intra-aortic balloon pumps
Authors: Kelly Julie , Malloy Rhynn , Knowles Danielle 
Published: June 2021

Abstract
Background
There is limited guidance regarding the use of anticoagulation in patients on intra-aortic balloon pumps (IABP). The purpose of this study is to compare the safety outcomes in anticoagulated versus non-anticoagulated patients with an IABP.

Methods
This was a single center, retrospective chart review of patients admitted to the coronary care unit or cardiac surgery unit who received an IABP from May 2015 to July 2018. Patients who were anticoagulated with heparin while on an IABP were compared to those who were not anticoagulated. Major endpoints included a composite of thrombotic events and a composite of bleeding events. The major composite endpoint of thrombotic events included the incidence of ischemic stroke, any venous thromboembolism, device thrombosis, and limb ischemia. The major composite endpoint of bleeding events included major access site bleeding, minor access site bleeding, major non-access site bleeding, and minor non-access site bleeding. Minor endpoints included any major endpoint events occurring within 24 and 48 h of IABP insertion, hospital length of stay, intensive care unit length of stay, and in-hospital mortality.

Results
A total of 185 patients were evaluated for inclusion and 147 were included in the final analysis. There were 82 and 65 patients in the heparin and non-heparin groups, respectively. The composite endpoint of thrombotic events occurred in 7.3 and 7.7% in the heparin and non-heparin groups, respectively (p = 1). The composite bleeding endpoint occurred in 20.7 and 20.0% in the heparin and non-heparin groups, respectively (p = 0.91). There were no differences found in minor endpoints between groups.

Conclusion
There were no significant differences found in major endpoints of bleeding and thrombotic events in patients who received anticoagulation while on an IABP versus those who did not receive anticoagulation.
A review of thromboembolic events in hospitalized COVID-19 patients
Authors: Fontelo Paul , Bastola Mrigendra M. , Zheng Zhaonian , Baik Seo Hyon 
Published: June 2021

Abstract
Context
A higher incidence of thromboembolic disorders in COVID-19 has been reported by many clinicians worldwide.

Objective, design and data sources
Selected studies found in PubMed that reported thromboembolic events were included for meta-analysis using weighted fixed and random effects. Data from 19 articles on cohort studies in patients diagnosed with COVID-19 and thromboembolic events, including thrombosis and embolism were included in this review.

Results
The likelihood for developing thromboembolic disorders in hospitalized COVID-19 patients was 0.28 (95% CI 0.21–0.36).

Conclusion
This study further validates the increased risk of VTE in COVID-19 patients when compared to healthy, non-hospitalized people, and hospitalized patients. These findings will be useful to researchers and medical practitioners caring for COVID-19 patients.
Global prevalence of physical activity for children and adolescents; inconsistencies, research gaps, and recommendations: a narrative review
Authors: Aubert Salomé , Brazo-Sayavera Javier , González Silvia A. , Janssen Ian , Manyanga Taru , Oyeyemi Adewale L. , Picard Patrick , Sherar Lauren B. , Turner Evan , Tremblay Mark S. 
Published: June 2021

Abstract
Background
One of the strategic actions identified in the Global Action Plan on Physical Activity (PA) 2018–2030 is the enhancement of data systems and capabilities at national levels to support regular population surveillance of PA. Although national and international standardized surveillance of PA among children and adolescents has increased in recent years, challenges for the global surveillance of PA persist. The aims of this paper were to: (i) review, compare, and discuss the methodological inconsistencies in children and adolescents’ physical activity prevalence estimates from intercontinental physical activity surveillance initiatives; (ii) identify methodological limitations, surveillance and research gaps.

Methods
Intercontinental physical activity surveillance initiatives for children and adolescents were identified by experts and through non-systematic literature searches. Prevalence of meeting PA guidelines by country, gender, and age were extracted when available. A tool was created to assess the quality of the included initiatives. Methods and PA prevalence were compared across data/studies and against the methodological/validity/translation differences.

Results
Eight intercontinental initiatives were identified as meeting the selection criteria. Methods and PA definition inconsistencies across and within included initiatives were observed, resulting in different estimated national prevalence of PA, and initiatives contradicting each other’s cross-country comparisons. Three findings were consistent across all eight initiatives: insufficient level of PA of children and adolescents across the world; lower levels of PA among girls; and attenuation of PA levels with age. Resource-limited countries, younger children, children and adolescents not attending school, with disability or chronic conditions, and from rural areas were generally under/not represented.

Conclusions
There are substantial inconsistencies across/within included initiatives, resulting in varying estimates of the PA situation of children and adolescents at the global, regional and national levels. The development of a new PA measurement instrument that would be globally accepted and harmonized is a global health priority to help improve the accuracy and reliability of global surveillance.
Clinical and psychosocial stress factors are associated with decline in physical activity over time in children with juvenile idiopathic arthritis
Authors: Heale Liane D. , Houghton Kristin M. , Rezaei Elham , Baxter-Jones Adam D. G. , Tupper Susan M. , Muhajarine Nazeem , Benseler Susanne M. , Boire Gilles , Cabral David A. , Campillo Sarah , Chédeville Gaëlle , Chetaille Anne-Laure , Dancey Paul , Duffy Ciaran , Duffy Karen Watanabe , Ellsworth Janet , Guzman Jaime , Huber Adam M. , Jurencak Roman , Lang Bianca , Laxer Ronald M. , Morishita Kimberly , Oen Kiem G. , Petty Ross E. , Ramsey Suzanne E. , Roth Johannes , Schneider Rayfel , Scuccimarri Rosie , Spiegel Lynn , Stringer Elizabeth , Tse Shirley M. L. , Tucker Lori B. , Turvey Stuart E. , Yeung Rae S. M. , Rosenberg Alan M. ,   for the BBOP Study Group
Published: June 2021

Abstract
Background
Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA).

Methods
In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores.

Results
At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score − 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = − 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4–3.1) to 24 months (median and IQR: 2.1, 1.4–2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p <  0.001).

Conclusion
Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.
Properties of the surface electromyogram following traumatic spinal cord injury: a scoping review
Authors: Balbinot Gustavo , Li Guijin , Wiest Matheus Joner , Pakosh Maureen , Furlan Julio Cesar , Kalsi-Ryan Sukhvinder , Zariffa Jose 
Published: June 2021

AbstractTraumatic spinal cord injury (SCI) disrupts spinal and supraspinal pathways, and this process is reflected in changes in surface electromyography (sEMG). sEMG is an informative complement to current clinical testing and can capture the residual motor command in great detail—including in muscles below the level of injury with seemingly absent motor activities. In this comprehensive review, we sought to describe how the sEMG properties are changed after SCI. We conducted a systematic literature search followed by a narrative review focusing on sEMG analysis techniques and signal properties post-SCI. We found that early reports were mostly focused on the qualitative analysis of sEMG patterns and evolved to semi-quantitative scores and a more detailed amplitude-based quantification. Nonetheless, recent studies are still constrained to an amplitude-based analysis of the sEMG, and there are opportunities to more broadly characterize the time- and frequency-domain properties of the signal as well as to take fuller advantage of high-density EMG techniques. We recommend the incorporation of a broader range of signal properties into the neurophysiological assessment post-SCI and the development of a greater understanding of the relation between these sEMG properties and underlying physiology. Enhanced sEMG analysis could contribute to a more complete description of the effects of SCI on upper and lower motor neuron function and their interactions, and also assist in understanding the mechanisms of change following neuromodulation or exercise therapy.
Heart rate variability as a strain indicator for psychological stress for emergency physicians during work and alert intervention: a systematic review
Authors: Thielmann Beatrice , Pohl Robert , Böckelmann Irina 
Published: June 2021

Abstract
Background
The workloads of emergency physicians are severe. The prevalence of burnout among emergency physicians is higher than with other physicians or compared to the general population. The analysis of heart rate variability (HRV) is a valid method for objective monitoring of workload. The aim of this paper is to systematically evaluate the literature on heart rate variability as an objective indicator for mental stress of emergency physicians.

Methods
A systematic literature review examining heart rate variability of emergency physicians in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement for reporting systematic reviews was performed. PubMed, Ovid, Cochrane Libary, Scopus, and Web of Science electronic databases were used. The methodological quality was evaluated by using a modified STARD for HRV.

Results
Two studies matched the inclusion criteria by using HRV between alert intervention and two other studies were considered that used HRV in other question areas. It showed an adaptation of HRV under stress. The studies were not comparable.

Conclusions
There is a need for occupational health studies that examine strains and stress of emergency physicians. The well-established parasympathetic mediated HRV parameters seem to be suitable parameters to objectify the stress.