bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the Relationship Between Age and Kidney Failure in Adults With Category 4 Chronic Kidney Disease
Authors: Al-Wahsh Huda , Lam Ngan N. , Liu Ping , Quinn Robert R. , Fiocco Marta , Hemmelgarn Brenda , Tangri Navdeep , Tonelli Marcello , Ravani Pietro 
Published: October 2020

Background: In people with severe chronic kidney disease (CKD), there is an inverse relationship between age and kidney failure. If this relationship is the same at any age (linear), one effect (hazard ratio) will be sufficient for accurate risk prediction; if it is nonlinear, the effect will vary with age. Objective: To investigate the relationship between age and kidney failure in adults with category G4 chronic kidney disease (G4 CKD). Methods: We performed a population-based study using linked administrative databases in Alberta, Canada, to study adults with G4 CKD (estimated glomerular filtration rate [eGFR] = 15-30 mL/min/1.73 m2) and without previously documented eGFR <15 mL/min/1.73 m2 or renal replacement. We used cause-specific Cox regression to model the relationship between age and the hazard of kidney failure (the earlier of eGFR <10 mL/min/1.73 m2 or receipt of renal replacement) and death, incorporating spline terms to capture any nonlinear effect of age. We included sex, diabetes mellitus, cardiovascular disease, albuminuria, and eGFR in all models. Results: Of the 27 823 participants (97 731 patient-years at risk; mean age = 76 years, ±13), 19% developed kidney failure and 51% died. The decline in the hazard of kidney failure associated with a given increase in age was not constant but became progressively larger as people aged; that is, the hazard ratio became progressively smaller (closer to 0). Assuming an eGFR of 25 mL/min/1.73 m2, for every 10-year increase in age, the hazard ratio declined from 0.76 (95% confidence interval = 0.73-0.79) at age 50 years to 0.43 (95% confidence interval = 34-56) at age 80 years in people without cardiovascular disease, and from 0.75 (95% confidence interval = 0.70-0.79) at age 50 years to 0.36 (95% confidence interval = 0.29-0.45) at age 80 years in people with cardiovascular disease. Conclusions: The relationship between kidney failure and age varies with age. An age-dependent effect, rather than a constant effect, needs to be specified to accurately predict risk. These findings have implications for risk prediction and advanced care planning.
Cost-of-illness trajectories among people with multiple sclerosis by comorbidity: A register-based prospective study in Sweden
Authors: Bütepage Greta , Esawi Ahmed , Alexanderson Kristina , Friberg Emilie , Murley Chantelle , Hillert Jan , Karampampa Korinna 
Published: October 2020

Background Comorbidities are common among people with multiple sclerosis (PwMS); yet, their impact on the cost-of-illness (COI) in MS is unknown. Objective Explore the heterogeneity in COI trajectories among newly diagnosed PwMS in relation to type of comorbidity. Methods A nationwide longitudinal cohort study, using prospectively collected Swedish register data for seven years. The COI/year of 639 PwMS diagnosed in 2006, when aged 25–60, was estimated until 2013. Using healthcare data, PwMS were categorised into six comorbidity groups: ocular; cardiovascular, genitourinary or cancer disease; musculoskeletal; mental; neurological other than MS; and injuries. One group of PwMS without comorbidity was also created. Group-based trajectory modelling was applied, examining different COI trajectories within each comorbidity group. Results Across the seven follow-up years, PwMS with mental comorbidities had the highest COI overall (€36,482). Four COI trajectories were identified within each comorbidity group; the largest trajectory had high healthcare costs and productivity losses (36.3%–59.6% of PwMS, across all comorbidity groups). 59.6% of PwMS with mental comorbidity had high healthcare costs and productivity losses. Conclusion High COI and heterogeneity in COI trajectories could be partly explained by the presence of chronic comorbidities in the year around MS diagnosis, including the presence of mental comorbidity.
An Examination of the Impact of Game-Based Geometric Shapes Education Software Usage on the Education of Students With Intellectual Disabilities
Authors: Demir Ümit 
Published: October 2020

Purpose: This study aims to research the impact of the e-learning environment, in which game-based education software was used, on the learning of students with intellectual disabilities. Design/Approach/Methods: The study group consisted of 34 students with intellectual disabilities studying at a special education vocational school in Çanakkale, Turkey. In this study, the true experimental method was used. For 5 weeks, the experimental group received blended learning that was supported by the usage of a game-based education software designed by the researcher, which includes interactive educational game applications. At the same time, control group students only received the teaching process in the classroom with the traditional teaching method. A course attitude scale and an achievement test were used for data collection. Findings: The analysis of the findings showed that there was a significant increase between pre-course and post-course attitudes and academic achievement scores of the students. There wasn’t a significant difference between pre-course and post-course attitudes and academic achievement scores according to the gender and academic achievement scores. Males’ academic achievement and attitude post-test scores were higher than females’ scores. Students having upper daily mobile devices usage experience had higher post-test and academic achievement scores than students having lower daily mobile devices usage experience. Originality/Value: This article has the potential to construct a new practice example as a supplement for analyzing the game-based educational software usage on the education of students with intellectual disabilities. As a pilot study, it provides a good sample for further investigations.
Issues and Challenges in Implementing Care Coordinator in Primary Healthcare in Malaysia: A Qualitative Study
Authors: Abdullah Zalilah , Abdul Aziz Siti Hajar , Sodri Nur Aliyah , Mohd Hanafiah Ainul Nadziha , Ibrahim Nor Idawaty , Johari Mohammad Zabri 
Published: October 2020

Background: Primary healthcare is the earliest gateway for patient care, and improvisations are often needed to accommodate the ever-increasing demand in public health. The Enhanced Primary Healthcare (EnPHC) initiative is aimed at improving such needs, and one core intervention is the introduction of a care coordinator (CC). The purpose of this study was to identify barriers and facilitators in implementing a new intervention in primary healthcare clinics. Methods: This qualitative exploration study. All healthcare providers who were involved in EnPHC at the intervention clinics were selected as participants. In-depth interviews and focus group discussions were carried out among healthcare providers working in the intervention clinic. Thematic analysis was used to categorize data, based on the consolidated framework for implementation research (CFIR) theoretical framework domains. Results: A total of 61 healthcare providers participated. All 5 domains with 19 CFIR constructs emerged from the analysis. Inner setting played a significant role in facilitating CC intervention, in which culture, networking, and collaboration and leadership engagement played an essential role in supporting CC activities. Although CC tasks are complex, concerns of losing clinical skill and resource constraints were identified as potential barriers in CC implementations. Criteria for appointing new CCs emerged from the characteristics of individual constructs, in which the individual must be familiar and interested in community health, have good communication skills, and at least 3 years’ experience in the primary healthcare setting. Conclusion: The implementation of the CC intervention faces varying challenges in different settings. This is partially resolved through teamwork, guidance from mentors, and support from superiors. The complexity of the responsibility of the CC intervention is perceived as both a validation and a burden. Above all, it is seen as paramount in EnPHC intervention.
Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data
Authors: Dodick David W. , Shewale Anand S. , Lipton Richard B. , Baum Seth J. , Marcus Steven C. , Silberstein Stephen D. , Pavlovic Jelena M. , Bennett Nathan L. , Young William B. , Viswanathan Hema N. , Doshi Jalpa A. , Weintraub Howard 
Published: October 2020

Introduction: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. Methods: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising “other significant underlying CV disease”; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. Results: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 “other CV disease” judged by the panel to constitute a “significant underlying CV disease” (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 “other significant underlying CV disease” (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an “other CV disease” endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. Conclusions: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.
Spine Patient Satisfaction With Telemedicine During the COVID-19 Pandemic: A Cross-Sectional Study
Authors: Satin Alexander M. , Shenoy Kartik , Sheha Evan D. , Basques Bryce , Schroeder Gregory D. , Vaccaro Alexander R. , Lieberman Isador H. , Guyer Richard D. , Derman Peter B. 
Published: October 2020

Study Design: Original research, cross-sectional study. Objectives: Evaluate patient satisfaction with spine care delivered via telemedicine. Identify patient- and visit-based factors associated with increased satisfaction and visit preference. Methods: Telemedicine visits with a spine surgeon at 2 practices in the United States between March and May 2020 were eligible for inclusion in the study. Patients were sent an electronic survey recording overall satisfaction, technical or clinical issues encountered, and preference for a telemedicine versus an in-person visit. Factors associated with poor satisfaction and preference of telemedicine over an in-person visit were identified using multivariate logistic regression. Results: A total of 772 responses were collected. Overall, 87.7% of patients were satisfied with their telemedicine visit and 45% indicated a preference for a telemedicine visit over an in-person visit if given the option. Patients with technical or clinical issues were significantly less likely to achieve 5 out of 5 satisfaction scores and were significantly more likely to prefer an in-person visit. Patients who live less than 5 miles from their surgeon’s office and patients older than 60 years were also significantly more likely to prefer in-person visits. Conclusions: Spine telemedicine visits during the COVID-19 pandemic were associated with high patient satisfaction. Additionally, 45% of respondents indicated a preference for telemedicine versus an in-patient visit in the future. In light of these findings, telemedicine for spine care may be a preferable option for a subset of patients into the future.
The Rose-Colored Glasses of Geriatric Fall Patients: Inconsistencies Between Knowledge of Risk Factors for and Actual Causes of Falls
Authors: Collins Courtney E. , Chandra Arnav , Nguyen Bryan , Schultz Kurt , Mathew Pawan , Chen Tiffany , Renshaw Savannah , Rose Karen M. , Santry Heena P. 
Published: October 2020

Background: Falls are the leading cause of fatal injury, and most common cause of non-fatal trauma, among older adults. We sought to elicit older patient’s perspectives on fall risks for the general population as well as contributions to any personal falls to identify opportunities to improve fall education. Methods: Ten patients with a history of falls from inpatient trauma and outpatient geriatric services were interviewed. Transcripts were analyzed independently by five individuals using triangulation and constant comparison (NVivo11, QSR International) to compare fall risks to fall causes. Results: All patients reported that either they (9/10 participants) or someone they knew (8/10) had fallen. Despite this, only two personally worried about falling. Patient perceptions of fall risks fell into seven major themes: physiologic decline (8/10); underestimating limitations (7/10); environmental hazards (7/10), lack of awareness/rushing (4/10), misuse/lack of walking aids (3/10); positional transitions (2/10), and improper footwear (1/10). In contrast, the most commonly reported causes of personal falls were lack of awareness/rushing (7/10), environmental hazards (3/10), misuse/lack of walking aids (2/10), improper footwear (2/10), physiologic decline (2/10), underestimating limitations (1/10) and positional transitions (1/10). In general tended to attribute their own falls to their surroundings and were less likely to attribute physical or psychological limitations. Conclusion: Despite participants identifying falls as a serious problem, they were unlikely to worry about falling themselves. Participants were able to identify common fall risks. However, when speaking about personal experience, they were more likely to blame environmental hazards or rushing, and minimized the role of physiologic decline and personal limitations.
Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Ueno Hiroo , Yoshida Kenichi , Shiozawa Yusuke , Nannya Yasuhito , Iijima-Yamashita Yuka , Kiyokawa Nobutaka , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Isobe Tomoya , Seki Masafumi , Kimura Shunsuke , Makishima Hideki , Nakagawa Masahiro M. , Kakiuchi Nobuyuki , Kataoka Keisuke , Yoshizato Tetsuichi , Nishijima Dai , Deguchi Takao , Ohki Kentaro , Sato Atsushi , Takahashi Hiroyuki , Hashii Yoshiko , Tokimasa Sadao , Hara Junichi , Kosaka Yoshiyuki , Kato Koji , Inukai Takeshi , Takita Junko , Imamura Toshihiko , Miyano Satoru , Manabe Atsushi , Horibe Keizo , Ogawa Seishi , Sanada Masashi 
Published: October 2020

Abstract
Recent genetic studies using high-throughput sequencing have disclosed genetic alterations in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, their effects on clinical outcomes have not been fully investigated. To address this, we comprehensively examined genetic alterations and their prognostic impact in a large series of pediatric B-ALL cases. We performed targeted capture sequencing in a total of 1003 pediatric patients with B-ALL from 2 Japanese cohorts. Transcriptome sequencing (n = 116) and/or array-based gene expression analysis (n = 120) were also performed in 203 (84%) of 243 patients who were not categorized into any disease subgroup by panel sequencing or routine reverse transcription polymerase chain reaction analysis for major fusions in B-ALL. Our panel sequencing identified novel recurrent mutations in 2 genes (CCND3 and CIC), and both had positive correlations with ETV6-RUNX1 and hypodiploid ALL, respectively. In addition, positive correlations were also newly reported between TCF3-PBX1 ALL with PHF6 mutations. In multivariate Cox proportional hazards regression models for overall survival, TP53 mutation/deletion, hypodiploid, and MEF2D fusions were selected in both cohorts. For TP53 mutations, the negative effect on overall survival was confirmed in an independent external cohort (n = 466). TP53 mutation was frequently found in IGH-DUX4 (5 of 57 [9%]) ALL, with 4 cases having 17p LOH and negatively affecting overall survival therein, whereas TP53 mutation was not associated with poor outcomes among NCI (National Cancer Institute) standard risk (SR) patients. A conventional treatment approach might be enough, and further treatment intensification might not be necessary, for patients with TP53 mutations if they are categorized into NCI SR.
Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64–labeled daratumumab
Authors: Krishnan Amrita , Adhikarla Vikram , Poku Erasmus K. , Palmer Joycelynne , Chaudhry Ammar , Biglang-awa Van Eric , Bowles Nicole , Nathwani Nitya , Rosenzweig Michael , Sahebi Firoozeh , Karanes Chatchada , Simpson Jennifer , Sanchez James F. , Yamauchi Dave , Parayno Maria , Chowdhury Arnab , Caserta Enrico , Marcucci Guido , Rockne Russell , Wu Anna M. , Wong Jeffrey , Forman Stephen J. , Colcher David , Yazaki Paul , Shively John , Pichiorri Flavia 
Published: October 2020

Abstract
18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.
Effective control ofStaphylococcus aureuslung infection despite tertiary lymphoid structure disorganisation
Authors: Regard Lucile , Martin Clémence , Teillaud Jean-Luc , Lafoeste Hélène , Vicaire Hugues , Ladjemi Maha Zohra , Ollame-Omvane Emilie , Sibéril Sophie , Burgel Pierre-Régis 
Published: October 2020

BackgroundTertiary lymphoid structures (TLS) are triggered by persistent bronchopulmonary infection withStaphylococcus aureus, but their roles remain elusive. The present study sought to examine the effects of B- and/or T-cell depletion onS. aureusinfection and TLS development (lymphoid neogenesis) in mice.MethodsC57Bl/6 mice were pre-treated with 1) an anti-CD20 monoclonal antibody (mAb) (B-cell depletion) or 2) an anti-CD4 and/or an anti-CD8 mAb (T-cell depletion) or 3) a combination of anti-CD20, anti-CD4 and anti-CD8 mAbs (combined B- and T-cell depletion) or 4) isotype control mAbs. After lymphocyte depletion, mice were infected by intratracheal instillation of agarose beads containingS. aureus(106 CFU per mouse). 14 days later, bacterial load and lung inflammatory cell infiltration were assessed by cultures and immunohistochemistry, respectively.Results14 days afterS. aureus-bead instillation, lung bacterial load was comparable between control and lymphocyte-depleted mice. While TLS were observed in the lungs of infected mice pre-treated with control mAbs, these structures were disorganised or abolished in the lungs of lymphocyte-depleted mice. The absence of CD20+B-lymphocytes had no effect on CD3+T-lymphocyte infiltration, whereas CD4+/CD8+T-cell depletion markedly reduced CD20+B-cell infiltration. Depletion of CD4+or CD8+T-cells separately had limited effect on B-cell infiltration, but led to the absence of germinal centres.ConclusionTLS disorganisation is not associated with loss of infection control in mice persistently infected withS. aureus.
NIMBus: a negative binomial regression based Integrative Method for mutation Burden Analysis
Authors: Zhang Jing , Liu Jason , McGillivray Patrick , Yi Caroline , Lochovsky Lucas , Lee Donghoon , Gerstein Mark 
Published: October 2020

Abstract
Background
Identifying frequently mutated regions is a key approach to discover DNA elements influencing cancer progression.
However, it is challenging to identify these burdened regions due to mutation rate heterogeneity across the genome and across different individuals. Moreover, it is known that this heterogeneity partially stems from genomic confounding factors, such as replication timing and chromatin organization. The increasing availability of cancer whole genome sequences and functional genomics data from the Encyclopedia of DNA Elements (ENCODE) may help address these issues.

Results
We developed a negative binomial regression-based Integrative Method for mutation Burden analysiS (NIMBus). Our approach addresses the over-dispersion of mutation count statistics by (1) using a Gamma–Poisson mixture model to capture the mutation-rate heterogeneity across different individuals and (2) estimating regional background mutation rates by regressing the varying local mutation counts against genomic features extracted from ENCODE. We applied NIMBus to whole-genome cancer sequences from the PanCancer Analysis of Whole Genomes project (PCAWG) and other cohorts. It successfully identified well-known coding and noncoding drivers, such as TP53 and the TERT promoter. To further characterize the burdening of non-coding regions, we used NIMBus to screen transcription factor binding sites in promoter regions that intersect DNase I hypersensitive sites (DHSs). This analysis identified mutational hotspots that potentially disrupt gene regulatory networks in cancer. We also compare this method to other mutation burden analysis methods.

Conclusion
NIMBus is a powerful tool to identify mutational hotspots. The NIMBus software and results are available as an online resource at github.gersteinlab.org/nimbus.