bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Role of the Platelet-Lymphocyte Ratio in Acute Ischemic Stroke Patients Undergoing Reperfusion Therapy: A Meta-Analysis
Authors: Sharma Divyansh , Bhaskar Sonu M. M. 
Published: July 2022

Background Both inflammation and thrombotic/hemostatic mechanisms may play a role in acute ischemic stroke (AIS) pathogenesis, and a biomarker, such as the platelet-to-lymphocyte ratio (PLR), considering both mechanisms may be of clinical utility. Objectives This meta-analysis sought to examine the effect of PLR on functional outcomes, early neurological changes, bleeding complications, mortality, and adverse outcomes in AIS patients treated with reperfusion therapy (RT). Design Systematic Review and Meta-Analysis Data Sources and Methods Individual studies were retrieved from the PubMed/Medline, EMBASE and Cochrane databases. References thereof were also consulted. Data were extracted using a standardised data sheet, and systematic reviews and meta-analyses on the association of admission (pre-RT) or delayed (post-RT) PLR with defined clinical and safety outcomes were conducted. In the case of multiple delayed PLR timepoints, the timepoint closest to 24 hours was selected. Results Eighteen studies (n=4878) were identified for the systematic review, of which 14 (n=4413) were included in the meta-analyses. PLR collected at admission was significantly negatively associated with 90-day good functional outcomes (SMD=−.32; 95% CI = −.58 to −.05; P=.020; z=−2.328), as was PLR collected at delayed timepoints (SMD=−.43; 95% CI = −.54 to −.32; P<.0001; z=−7.454). PLR at delayed timepoints was also significantly negatively associated with ENI (SMD=−.18; 95% CI = −.29 to −.08; P=.001. Conversely, the study suggested that a higher PLR at delayed timepoints may be associated with radiological bleeding and mortality. The results varied based on the type of RT administered. Conclusions A higher PLR is associated with worse outcomes after stroke in terms of morbidity, mortality, and safety outcomes after stroke.
International Classification of Diseases clinical coding training: An international survey
Authors: Otero Varela Lucia , Doktorchik Chelsea , Wiebe Natalie , Southern Danielle A , Knudsen Søren , Mathur Pallavi , Quan Hude , Eastwood Cathy A 
Published: July 2022

Background The International Classification of Diseases (ICD) is widely used by clinical coders worldwide for clinical coding morbidity data into administrative health databases. Accordingly, hospital data quality largely depends on the coders’ skills acquired during ICD training, which varies greatly across countries. Objective To characterise the current landscape of international ICD clinical coding training. Method An online questionnaire was created to survey the 194 World Health Organization (WHO) member countries. Questions focused on the training provided to clinical coding professionals. The survey was distributed to potential participants who met specific criteria, and to organisations specialised in the topic, such as WHO Collaborating Centres, to be forwarded to their representatives. Responses were analysed using descriptive statistics. Results Data from 47 respondents from 26 countries revealed disparities in all inquired topics. However, most participants reported clinical coders as the primary person assigning ICD codes. Although training was available in all countries, some did not mandate training qualifications, and those that did differed in type and duration of training, with college or university degree being most common. Clinical coding certificates most frequently entailed passing a certification exam. Most countries offered continuing training opportunities, and provided a range of support resources for clinical coders. Conclusion Variability in clinical coder training could affect data collection worldwide, thus potentially hindering international comparability of health data. Implications These findings could encourage countries to improve their resources and training programs available for clinical coders and will ultimately be valuable to the WHO for the standardisation of ICD training.
Determining Factors Influencing RAS Inhibitors Re-Initiation in ICU: A Modified Delphi Method
Authors: Dahel Hadjer , Lafrance Jean-Philippe , Patenaude Mathilde , Kilpatrick Kelley , Beaubien-Souligny William , Moreau Mathieu , Wang Han Ting 
Published: July 2022

Background: Renin-angiotensin system inhibitors (RASi) are not re-initiated for almost a quarter of patients who suffered acute kidney injury 6 months after discharge. This discontinuation might be partly explained by the nephrotoxicity of these medications, yet they remain of benefit, especially for patients with heart failure. Objective: To determine the factors deemed by clinicians to influence RASi re-initiation and set threshold values for important safety parameters. Design: Three-round modified online Delphi survey. Setting: The study was conducted in Quebec, Canada. Participants: Twenty clinicians from nephrology, intensive care medicine, and internal medicine. Measurements: The factors’ importance was rated on 4-point Likert-type scale, ranging from “not important” to “very important” by the panelists. Methods: We conducted a brief literature review to uncover possible influencing factors followed by a 3-round modified Delphi survey to establish a consensus on the importance of these factors. Results: We recruited 20 clinicians (7 nephrologists, 3 internists, and 10 intensive care physicians). We created a list of 25 factors, 15 of which met consensus. Eleven of these factors, including serum creatinine, glomerular filtration rate, and acute kidney injury (AKI) stage, were deemed as important while 4, such as responsibility ambiguity and absence of feedback, were deemed as not important. The majority of the 10 factors which did not meet consensus were related to the clinical setting, such as a pharmacist follow-up and the required time to ensure optimal RASi re-initiation. Limitations: Quebec clinicians’ agreement might not reflect the opinion of the rest of Canada. The survey measures clinicians’ belief rather than their actual practice. Conclusion: Renin-angiotensin system inhibitors re-initiation is a rather complex concept which encompasses several factors. Our research uncovered some of these factors which may be used to develop guidelines on optimal RASi re-initiation.
Healthy Lifestyles Associated With Socioeconomic Determinants in the Older Adult Population
Authors: Roldán González Elizabeth , Lerma Castaño Piedad Rocio , Aranda Zemanate Adriana Yulieth , Caicedo Muñoz Ángela Giovana , Bonilla Santos Gisella 
Published: July 2022

Introduction/Objective: The evaluation of lifestyle in older adults and the study of socioeconomic determinants becomes an essential indicator of the health conditions of older adults. The purpose of this study was to establish the relationship between socioeconomic factors and healthy lifestyles in older adults. Methods: Study with a quantitative approach, descriptive type, non-experimental design, cross-sectional in a sample of 407 elderlies who have applied a self-designed instrument for socioeconomic characterization and the FANTASTIC test to assess lifestyle. For data analysis, a bivariate analysis was applied using chi2 and multivariate analysis using ordinal logistic regression. Results: 53% of elderlies aged between 60 and 70 years reported their lifestyle as excellent and very good. Age, average household income, and perceived health status are associated with healthy lifestyles in older adults. Conclusions: This study found that in addition to socioeconomic determinants, self-perceived health is a factor that influences the lifestyles of this population.
Effect of Sleep-Related Symptoms on Recovery From a Sport-Related Concussion
Authors: DuPrey Kevin M. , Char Amber S. , Loose Sean R. , Suffredini Michael V. , Walpole Kevin , Cronholm Peter F. 
Published: July 2022

Background: Sleep issues are commonly reported in athletes after a sport-related concussion (SRC). Further studies are needed to evaluate screening methods for sleep disturbances and the risk of persisting symptoms after an SRC. Purpose: To evaluate the association between the Sport Concussion Assessment Tool 5 (SCAT5) symptoms of trouble falling asleep, fatigue (or low energy), and drowsiness and the risk of persisting symptoms (≥28 days to recovery) in adolescent athletes. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 519 athletes aged 13 to 18 years reported any sleep-related symptoms with an SRC, scored as none (0), mild (1-2), moderate (3-4), or severe (5-6), at their initial office visit (median, 5.4 days after an SRC). Scores were correlated with the risk of persisting symptoms. A composite “sleep cluster” score (range, 0-18) was calculated by summing the SCAT5 component items for trouble falling asleep, fatigue, and drowsiness. Results: The results indicated that, compared with athletes who reported that they did not have each symptom, (1) athletes who reported mild, moderate, or severe trouble falling asleep were 3.0, 4.6, and 6.7 times more likely to have persisting symptoms, respectively; (2) athletes reporting mild, moderate, or severe fatigue (or low energy) were 2.6, 4.8, and 7.6 times more likely to have persisting symptoms, respectively; and (3) athletes reporting mild, moderate, or severe drowsiness were 1.9, 4.6, and 6.8 times more likely to have persisting symptoms, respectively ( P < .001 for all). For every 1-point increase in the sleep cluster score, there was a 1.2-fold increased risk of persisting symptoms and an additional 2.4 days of recovery required ( P < .001 for both). Conclusion: Athletes who reported mild, moderate, or severe sleep-related symptoms on the SCAT5 were at a proportionally increased risk of persisting symptoms at the initial office visit.
Professional Quality of Life Among Nurses: Compassion Satisfaction, Burnout, and Secondary Traumatic Stress: A Multisite Study
Authors: Bahari Ghareeb , Asiri Khulud , Nouh Nariman , Alqahtani Naji 
Published: July 2022

Introduction Increased stressors and decreased job satisfaction are major challenges in nursing. Important factors of better professional quality of life include compassion satisfaction, burnout, and secondary traumatic stress. It is critical to assess these factors to help improve nurses’ clinical practices. Objective The purpose of this study was to determine the relationships between the three factors and associated factors. Methods A cross-sectional, multisite study was conducted on a convenience sample of 464 nurses working at three public hospitals in Saudi Arabia. The Professional Quality of Life Version 5 was used to collect data. Bivariate and multivariate analyses were run using SPSS. Results Scores were slightly moderate on the compassion satisfaction, burnout, and secondary traumatic stress levels. Compassion satisfaction was statistically significantly and negatively associated with burnout. A statistically significant relationship was reported between compassion satisfaction and secondary traumatic stress. Further, there was a statistically significant association between burnout and secondary traumatic stress. In regression, only the secondary traumatic stress model was statistically significant. Conclusions Nurse managers should use highly standard guidelines to reduce secondary traumatic stress levels. Further actions addressing potential issues for improving compassion satisfaction and reducing burnout levels among nurses are also recommended.
Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma
Authors: Elsawy Mahmoud , Chavez Julio C. , Avivi Irit , Larouche Jean-François , Wannesson Luciano , Cwynarski Kate , Osman Keren , Davison Kelly , Rudzki Jakob D. , Dahiya Saurabh , Dorritie Kathleen , Jaglowski Samantha , Radford John , Morschhauser Franck , Cunningham David , Martin Garcia-Sancho Alejandro , Tzachanis Dimitrios , Ulrickson Matthew L. , Karmali Reem , Kekre Natasha , Thieblemont Catherine , Enblad Gunilla , Dreger Peter , Malladi Ram , Joshi Namita , Wang Wei-Jhih , Solem Caitlyn T. , Snider Julia Thornton , Cheng Paul , To Christina , Kersten Marie José 
Published: July 2022

AbstractHere, we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy vs standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 study of axicabtagene ciloleucel (axi-cel) vs SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for Quality of Life Questionnaire-Core 30 (QLQ-C30) physical functioning, global health status/QoL, and EQ-5D-5L visual analog scale (VAS) were tested using mixed-effects models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 global health status/QoL (estimated difference 18.1 [95% confidence interval (CI), 12.3-23.9]), physical functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P &lt; .0001 for all). At day 150, scores significantly favored axi-cel vs SOC for global health status/QoL (9.8 [95% CI, 2.6-17.0]; P = .0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P = .0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03391466.
Moderate-intensity aerobic exercise vs desmopressin in adolescent males with mild hemophilia A: a randomized trial
Authors: Kumar Riten , Dunn Amy L. , Schneiderman Jane E. , Gonzales Anne , Bouskill Vanessa , Widener Pamela , Stanek Joseph , Pluthero Fred G. , Waller Amanda , Tarango Cristina , Ahuja Sanjay , Kerlin Bryce A. , Kahr Walter H. A. , Rand Margaret L. , Lillicrap David , Carcao Manuel 
Published: July 2022

AbstractPersons with mild hemophilia A (HA) may use intranasal desmopressin prior to sports participation. Desmopressin is expensive and can cause vomiting, headache, palpitation, and occasionally seizures. Our group has previously documented a 2.3-fold increase in factor VIII activity (FVIII:C) in adolescents with mild HA after moderate-intensity aerobic exercise. Herein, we report principal findings of a randomized trial of intranasal desmopressin vs a standardized, moderate-intensity aerobic exercise regimen in adolescents with mild HA. Our primary objective was to compare the change in FVIII:C associated with these 2 interventions. We also examined changes in hemostatic parameters arising from their sequential administration. The study was conducted simultaneously at the Hospital for Sick Children, Canada, and Nationwide Children’s Hospital, USA. Thirty-two eligible male adolescents (mean age ± standard deviation: 16.1 ± 2.6 years) with mild HA (mean baseline FVIII:C: 27.9% ± 18.4%) were randomized to 1 of 4 study arms (desmopressin followed by exercise, desmopressin alone, exercise followed by desmopressin, and exercise alone). Blood work was obtained at baseline and at 3 subsequent time-points. Participants randomized to exercise cycled on an ergometer for approximately 12 minutes, with the final 3 minutes at 85% of their predicted maximum heart rate. Standard weight-based dosing of desmopressin was used. Mean immediate increase in FVIII:C was 1.7-fold with exercise compared with 1.9-fold with desmopressin (noninferiority, P = .04). Exercise-induced improvement in hemostatic parameters including FVIII:C was brief compared with more sustained improvements seen with desmopressin. More than 60% of participants randomized to receive both exercise and desmopressin achieved normal (&gt;50%) FVIII:C, 75 and 135 minutes into the study protocol.
Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR inRUNX1deficiency
Authors: Jalagadugula Gauthami , Mao Guangfen , Goldfinger Lawrence E. , Wurtzel Jeremy , Del Carpio-Cano Fabiola , Lambert Michele P. , Estevez Brian , French Deborah L. , Poncz Mortimer , Rao A. Koneti 
Published: July 2022

AbstractTranscription factor RUNX1 is a master regulator of hematopoiesis and megakaryopoiesis. RUNX1 haplodeficiency (RHD) is associated with thrombocytopenia and platelet granule deficiencies and dysfunction. Platelet profiling of our study patient with RHD showed decreased expression of RAB31, a small GTPase whose cell biology in megakaryocytes (MKs)/platelets is unknown. Platelet RAB31 messenger RNA was decreased in the index patient and in 2 additional patients with RHD. Promoter-reporter studies using phorbol 12-myristate 13-acetate–treated megakaryocytic human erythroleukemia cells revealed that RUNX1 regulates RAB31 via binding to its promoter. We investigated RUNX1 and RAB31 roles in endosomal dynamics using immunofluorescence staining for markers of early endosomes (EEs; early endosomal autoantigen 1) and late endosomes (CD63)/multivesicular bodies. Downregulation of RUNX1 or RAB31 (by small interfering RNA or CRISPR/Cas9) showed a striking enlargement of EEs, partially reversed by RAB31 reconstitution. This EE defect was observed in MKs differentiated from a patient-derived induced pluripotent stem cell line (RHD-iMKs). Studies using immunofluorescence staining showed that trafficking of 3 proteins with distinct roles (von Willebrand factor [VWF], a protein trafficked to α-granules; epidermal growth factor receptor; and mannose-6-phosphate) was impaired at the level of EE on downregulation of RAB31 or RUNX1. There was loss of plasma membrane VWF in RUNX1- and RAB31-deficient megakaryocytic human erythroleukemia cells and RHD-iMKs. These studies provide evidence that RAB31 is downregulated in RHD and regulates megakaryocytic vesicle trafficking of 3 major proteins with diverse biological roles. EE defect and impaired vesicle trafficking is a potential mechanism for the α-granule defects observed in RUNX1 deficiency.
Differences in wild-type– and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies
Authors: Foley Jonathan H. , Shehu Erald , Riddell Anne , Gray Elaine , Goodale Andrew , Yu I-Mei , Verhoef Daniël , Little John , Shattock Diane , Kitchen Steve , Chowdary Pratima , Corbau Romuald , Nathwani Amit C. 
Published: July 2022

AbstractAdeno-associated virus (AAV) gene therapy has the potential to functionally cure hemophilia B by restoring factor (F)IX concentrations into the normal range. Next-generation AAV therapies express a naturally occurring gain-of-function FIX variant, FIX-Padua (R338L-FIX), that increases FIX activity (FIX:C) by approximately eightfold compared with wild-type FIX (FIX-WT). Previous studies have shown that R338L-FIX activity varies dramatically across different clinical FIX:C assays, which complicates the monitoring and management of patients. To better understand mechanisms that contribute to R338L-FIX assay discrepancies, we characterized the performance of R338L-FIX in 13 1-stage clotting assays (OSAs) and 2 chromogenic substrate assays (CSAs) in a global field study. This study produced the largest R338L-FIX assay dataset to date and confirmed that clinical FIX:C assay results vary over threefold. Both phospholipid and activating reagents play a role in OSA discrepancies. CSA generated the most divergent FIX:C results. Manipulation of FIX:C CSA kits demonstrated that specific activity gains for R338L-FIX were most profound at lower FIX:C concentrations and that these effects were enhanced during the early phases of FXa generation. Supplementing FX into CSA had the effect of dampening FIX-WT activity relative to R338L-FIX activity, suggesting that FX impairs WT tenase formation to a greater extent than R338L-FIX tenase. Our data describe the scale of R338L-FIX assay discrepancies and provide insights into the causative mechanisms that will help establish best practices for the measurement of R338L-FIX activity in patients after gene therapy.
A comprehensive prognostic and immune analysis of enhancer RNA identifies IGFBP7-AS1 as a novel prognostic biomarker in Uterine Corpus Endometrial Carcinoma
Authors: Liu Jinhui , Yin Jian , Wang Yuanyuan , Cai Lixin , Geng Rui , Du Mulong , Zhong Zihang , Ni Senmiao , Huang Xiaohao , Yu Hao , Bai Jianling 
Published: July 2022

Abstract
Background
Long non-coding RNAs (lncRNA) have been implicated in a hand of studies that supported an involvement and co-operation in Uterine Corpus Endometrial Carcinoma (UCEC). Enhancer RNAs (eRNA), a functional subtype of lncRNA, have a key role throughout the genome to guide protein production, thus potentially associated with diseases.

Methods
In this study, we mainly applied the Cancer Genome Atlas (TCGA) dataset to systematically discover crucial eRNAs involving UCEC. For the key eRNAs in UCEC, we employed RT-qPCR to compare eRNA expression levels in tumor tissues and paired normal adjacent tissues from UCEC patients for validation. Furthermore, the relationships between the key eRNAs and immune activities were measured from several aspects, including the analysis for tumor microenvironment, immune infiltration cells, immune check point genes, tumor mutation burden, and microsatellite instability, as well as m6A related genes. Finally, the key eRNAs were verified by a comprehensive pan-cancer analysis.

Results
IGFBP7 Antisense RNA 1 (IGFBP7-AS1) was identified as the key eRNA for its expression patterns of low levels in tumor tissues and favorable prognostic value in UCEC correlated with its target gene IGFBP7. In RT-qPCR analysis, IGFBP7-AS1 and IGFBP7 had down-regulated expression in tumor tissues, which was consistent with previous analysis. Moreover, IGFBP7-AS1 was found closely related with immune response in relevant immune analyses. Besides, IGFBP7-AS1 and its target gene IGFBP7 correlated with a multi-omics pan-cancer analysis.

Conclusions
Finally, we suggested that IGFBP7-AS1 played a key role in impacting on clinical outcomes of UCEC patients for its possible influence on immune activity.