bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levonorgestrel-Releasing Intrauterine System Versus Endometrial Ablation for Heavy Menstrual Bleeding
Authors: Beelen Pleun , van den Brink Marian J. , Herman Malou C. , Geomini Peggy M. A. J. , Dekker Janny H. , Duijnhoven Ruben G. , Mak Nienke , van Meurs Hannah S. , Coppus Sjors F. , van der Steeg Jan Willem , Eising Heleen P. , Massop-Helmink Diana S. , Klinkert Ellen R. , Nieboer Theodoor E. , Timmermans Anne , van der Voet Lucet F. , Veersema Sebastiaan , Smeets Nicol A. C. , Schutte Joke M. , van Baal Marchien , Bossuyt Patrick M. , Mol Ben Willem J. , Berger Marjolein Y. , Bongers Marlies Y. 
Published: May 2021

(Abstracted from Am J Obstet Gynecol 2021;224(2):187.e1–187.e10)
Heavy menstrual bleeding (HMB) can negatively influence physical activity, work productivity, and sexual life and therefore has a major impact on women's quality of life (QoL). The National Institute for Health and Care Excellence guidelines recommend the levonorgestrel-releasing intrauterine system (LNG-IUS) as the treatment of first choice for HMB.
Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial
Authors: Ferrante Kimberly L. , Wasenda Erika J. , Jung Carrie E. , Adams-Piper Emily R. , Lukacz Emily S. 
Published: May 2021

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27(2):112–117)
Recurrent urinary tract infection (rUTI) is defined as at least 2 UTIs in a 6-month span or 3 UTIs in a 1-year span. Postmenopausal status is a well-described risk factor for rUTI, with declining levels of systemic estrogen hypothesized as a contributory biological mechanism.
Chimeric Antigen Receptor T-Cell Therapeutics for Multiple Myeloma
Authors: Wang Bo , Rajeeve Sridevi , Madduri Deepu 
Published: May 2021

Abstract
Chimeric antigen receptor (CAR) T-cell therapy has quickly emerged as a highly promising treatment for patients with relapsed and refractory multiple myeloma. There are numerous candidates under development, each with their unique characteristics and points of differentiation. The most recent US Food and Drug Administration approval of the first B-cell maturation antigen–targeted CAR-T cell therapy on March 26, 2021, has paved a path forward for the eventual evaluation of more of these investigational agents undergoing clinical trials. Herein, we highlight, from a clinical development perspective, the CAR-T cell therapies farthest along in development with updated data from the American Society of Hematology 2020 annual meeting. We also discuss potential paths of overcoming resistance to these therapies and the future direction for CAR-T cell therapeutics in multiple myeloma.
Feasibility of Cardiac Computed Tomography for the Evaluation of Ventricular Function in Postoperative Children With Congenital Heart Disease: Comparison With Cardiac Magnetic Resonance Imaging
Authors: Xie Wei-Hui , Guo Chen , Hu Li-Wei , Ouyang Rong-Zhen , Yao Xiao-Fen , Sun Ai-Min , Qiu Hai-Sheng , Yan Qin , Zhu Ya-Xin , Wang Qian , Zhong Yu-Min 
Published: May 2021

Objective
We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference.

Methods
Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements.

Results
All functional parameters showed no significant difference (P > 0.05) and were well-correlated (r > 0.5, P < 0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient > 0.9).

Conclusions
Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.
Head-to-head Comparison of Qualitative Radiologist Assessment With Automated Quantitative Computed Tomography Analysis for Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation
Authors: Sharifi Husham , Guenther Zachary D. , Leung Ann N.C. , Johnston Laura , Lai Yu K. , Hsu Joe L. , Guo H. Henry 
Published: May 2021

Purpose:
Computed tomography (CT) findings of bronchiolitis obliterans syndrome (BOS) can be nonspecific and variable. This study aims to measure the incremental value of automated quantitative lung CT analysis to clinical CT interpretation. A head-to-head comparison of quantitative CT lung density analysis by parametric response mapping (PRM) with qualitative radiologist performance in BOS diagnosis was performed.

Materials and Methods:
Inspiratory and end-expiratory CTs of 65 patients referred to a post–bone marrow transplant lung graft-versus-host-disease clinic were reviewed by 3 thoracic radiologists for the presence of mosaic attenuation, centrilobular opacities, airways dilation, and bronchial wall thickening. Radiologists’ majority consensus diagnosis of BOS was compared with automated PRM air trapping quantification and to the gold-standard diagnosis of BOS as per National Institutes of Health (NIH) consensus criteria.

Results:
Using a previously established threshold of 28% air trapping on PRM, the diagnostic performance for BOS was as follows: sensitivity 56% and specificity 94% (area under the receiver operator curve [AUC]=0.75). Radiologist review of inspiratory CT images alone resulted in a sensitivity of 80% and a specificity of 69% (AUC=0.74). When radiologists assessed both inspiratory and end-expiratory CT images in combination, the sensitivity was 92% and the specificity was 59% (AUC=0.75). The highest performance was observed when the quantitative PRM report was reviewed alongside inspiratory and end-expiratory CT images, with a sensitivity of 92% and a specificity of 73% (AUC=0.83).

Conclusions:
In the CT diagnosis of BOS, qualitative expert radiologist interpretation was noninferior to quantitative PRM. The highest level of diagnostic performance was achieved by the combination of quantitative PRM measurements with qualitative image feature assessments.
Frailty and Kidney Transplantation: A Systematic Review and Meta-analysis
Authors: Quint Evelien E. , Zogaj Donika , Banning Louise B.D. , Benjamens Stan , Annema Coby , Bakker Stephan J.L. , Nieuwenhuijs-Moeke Gertrude J. , Segev Dorry L. , McAdams-DeMarco Mara A. , Pol Robert A. 
Published: May 2021

Background.
Frailty is a multidimensional condition and is the result of the body’s age-associated decline in physical, cognitive, physiological, and immune reserves. The aim of this systematic review is to assess the quality of evidence of the included studies, determine the prevalence of frailty among kidney transplant candidates, and evaluate the relationship between frailty and associated patient characteristics and outcomes after kidney transplantation.

Methods.
A systematic search was performed for relevant literature on frailty and kidney transplantation. This was followed by a meta-analysis for patient characteristics and outcomes reported by a minimum of 2 studies including mean age, gender, mean body mass index, type of kidney transplantation, dialysis, previous kidney transplantation, comorbidities, hypertension, race, preemptive kidney transplantation, delayed graft function, and length of stay.

Results.
A total of 18 studies were included in the systematic review and 14 of those studies were suitable for meta-analysis. The overall pooled prevalence of frailty before transplantation was estimated at 17.1% (95% confidence interval [CI], 15.4-18.7). Frailty was significantly associated with higher age (mean difference, 3.6; 95% CI, 1.4-5.9), lower rate of preemptive transplantation (relative risk, 0.60; 95% CI, 0.4-0.9), longer duration of delayed graft function (relative risk, 1.80; 95% CI, 1.1-3.0), and length of stay longer than 2 wk (odds ratio, 1.64; 95% CI, 1.2-2.3).

Conclusions.
One in 6 kidney transplant recipients is frail before transplantation. The presence of frailty is associated with lower rates of preemptive transplantation, older recipient age, higher rates of delayed graft function, and longer length of stay. Future research is required to explore the association of frailty with other adverse outcomes after kidney transplantation and the effects of intervention programs to improve the different frailty domains.
Personalized, Multisession, Multichannel Transcranial Direct Current Stimulation in Medication-Refractory Focal Epilepsy: An Open-Label Study
Authors: Kaye Harper Lee , San-Juan Daniel , Salvador Ricardo , Biagi Maria Chiara , Dubreuil-Vall Laura , Damar Ugur , Pascual-Leone Alvaro , Ruffini Giulio , Shafi Mouhsin M. , Rotenberg Alexander 
Published: May 2021

Purpose:
Animal and proof-of-principle human studies suggest that cathodal transcranial direct current stimulation may suppress seizures in drug-resistant focal epilepsy. The present study tests the safety, tolerability, and effect size of repeated daily cathodal transcranial direct current stimulation in epilepsy have not been established, limiting development of clinically meaningful interventions.

Methods:
We conducted a 2-center, open-label study on 20 participants with medically refractory, focal epilepsy, aged 9 to 56 years (11 women and 9 children younger than18 years). Each participant underwent 10 sessions of 20 minutes of cathodal transcranial direct current stimulation over 2 weeks. Multielectrode montages were designed using a realistic head model–driven approach to conduct an inhibitory electric field to the target cortical seizure foci and surrounding cortex to suppress excitability and reduce seizure rates. Patients recorded daily seizures using a seizure diary 8 weeks prior, 2 weeks during, and 8 to 12 weeks after the stimulation period.

Results:
The median seizure reduction was 44% relative to baseline and did not differ between adult and pediatric patients. Three patients experienced an increase in seizure frequency of >50% during the stimulation period; in one, a 36% increase in seizure frequency persisted through 12 weeks of follow-up. Otherwise, participants experienced only minor adverse events—the most common being scalp discomfort during transcranial direct current stimulation.

Conclusions:
This pilot study supports the safety and efficacy of multifocal, personalized, multichannel, cathodal transcranial direct current stimulation for adult and pediatric patients with medication-refractory focal epilepsy, although identifies a possibility of seizure exacerbation in some. The data also provide insight into the effect size to inform the design of a randomized, sham-stimulation controlled trial.
Neural bases of Frustration-Aggression Theory: A multi-domain meta-analysis of functional neuroimaging studies
Authors: Dugré Jules R. , Potvin Stéphane 
Published: May 2021

ABSTRACTEarly evidence suggests that unexpected non-reward may increase the risk for aggressive behaviors. Despite the growing interest in understanding brain functions that may be implicated in aggressive behaviors, the neural processes underlying such frustrative events remain largely unknown. Furthermore, meta-analytic results have produced discrepant results, potentially due to substantial differences in the definition of anger/aggression constructs. Therefore, coordinate-based meta-analyses on unexpected non-reward and retaliatory behaviors in healthy subjects were conducted. Conjunction analyses were further examined to discover overlapping brain activations across these meta-analytical maps. Frustrative non-reward deactivated the orbitofrontal cortex, ventral striatum and posterior cingulate cortex, whereas increased activations were observed in midcingulo-insular regions, as well as dorsomedial prefrontal cortex, amygdala, thalamus and periaqueductal gray, when using liberal threshold. Retaliation activated of midcingulo-insular regions, the dorsal caudate and the primary somatosensory cortex. Conjunction analyses revealed that both strongly activated midcingulo-insular regions. Our results underscore the role of anterior midcingulate/pre-supplementary motor area and fronto-insular cortex in both frustration and retaliatory behaviors. A neurobiological framework for understanding frustration-based impulsive aggression is provided.
A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model
Authors: Donneyong Macarius M. , Zhu Yuxi , Chang Teng-Jen , Zhang Pengyue , Li Yiting , Hunold Katherine M. , Chiang ChienWei , Unroe Kathleen , Caterino Jeffrey M. , Li Lang 
Published: May 2021

AbstractAimsTo describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs.MethodsA retrospective new-user cohort study design was used to identify (N=160828) patients who concurrently initiated CYP3A4-inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104774) vs. other statins (unexposed, n = 56054) from the MarketScan Commercial claims database (2012 – 2017). These groups were matched (2:1) through propensity score-matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs, vs. unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities.ResultsPatients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4 [95% CI: 71.1, 71.6] vs. 73.3 [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4 [95% CI: 3.3, 3.5] vs. 3.2 [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0 [95% CI: 20.8, 21.3] vs. 19.5 [95% CI: 19.2, 19.8]) directly after concurrently starting stains and CYP3A. Subsequent to experiencing an ADE, those exposed to statin DDIs were still less likely to discontinue statin therapy but were significantly more likely to discontinue CYP3A4-inhibitor therapy.ConclusionWhile statin DDI exposure was associated with higher likelihood of ADEs, this did not increase the risk of premature statin discontinuation among patients exposed to statin DDIs, versus unexposed.
Identifying Patterns of ALS Progression from Sparse Longitudinal Data
Authors: Ramamoorthy Divya , Severson Kristen , Ghosh Soumya , Sachs Karen ,   Answer ALS, Glass Jonathan D. , Fournier Christina N. ,   Pooled Resource Open-Access ALS Clinical Trials Consortium, Berry James , Ng Kenney , Fraenkel Ernest 
Published: May 2021

AbstractAmyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that is complex in its onset, pattern of spread, and disease progression. The heterogeneity of ALS makes it extremely challenging to determine if a disease modifying therapy is effectively slowing progression. While accurately modeling ALS progression is critical to developing therapeutics, current computational methods fail to capture the complexity of disease progression. We aimed to robustly characterize disease progression patterns in ALS.We obtained data from four clinical cohorts that cover more than 3,500 patients and include both observational and clinical trial studies. To determine whether there were common patterns of disease progression, we developed an approach based on a Mixture of Gaussian Processes (MoGP) to model longitudinal clinical data. Our approach automatically identifies clusters of patients who show similar disease progression patterns, modeling their average trajectory and the spread of the distribution in each cluster. Importantly, the method does not require any prior knowledge of the expected number of clusters.The MoGP approach revealed that ALS progression, as measured using the ALS functional rating scale (ALSFRS-R) or forced vital capacity, is often non-linear with periods of stable disease preceded or followed by rapid decline. Patterns of progression in ALSFRS-R were robust to sparse data. When at least one year of longitudinal data were available, MoGP predictions were significantly more accurate than linear models, which are commonly used in clinical trials. Progression patterns were consistent across different cohorts despite differences in the frequency of data collection and the lengths of follow-up periods. We further showed that clusters identified from one large, publicly available study population could be used to stratify unseen participants in other studies. We also showed that these progression trajectories correspond with survival outcomes.This work highlights the importance of modeling nonlinear disease progression for developing more advanced clinical trial endpoint analysis models. In ALS, sporadic, rapid decline (“functional cliffs”) and sigmoidal patterns in disease progression in untreated patients may obscure detection of therapeutic efficacy if linear models are used. We provide a pre-trained computational model of observed clinical patterns that can be used by others to analyze new ALS patient cohorts. We expect that the MoGP approach can also be applied to additional ALS outcome measures and to other progressive diseases. Our results provide a critical advance in characterizing the complex disease progression patterns of ALS.
Performance of polygenic risk scores for cancer prediction in a racially diverse academic biobank
Authors: Wang Louise , Desai Heena , Verma Shefali S. , Le Anh , Hausler Ryan , Verma Anurag , Judy Renae , Doucette Abigail , Gabriel Peter E. ,   Regeneron Genetics Center, Nathanson Katherine L. , Damrauer Scott , Mowery Danielle L. , Ritchie Marylyn D. , Kember Rachel L. , Maxwell Kara N. 
Published: May 2021

ABSTRACTPurposeGenome-wide association studies (GWAS) have identified hundreds of single nucleotide polymorphisms (SNPs) significantly associated with several cancers, but the predictive ability of polygenic risk scores (PRS) is unclear, especially among non-Whites.MethodsGenome-wide genotype data was available for 20,079 individuals enrolled in an academic biobank. PRS were derived from significant DNA variants for 15 cancers. We determined the discriminatory accuracy of each cancer-specific PRS in patients of genetically-determined African and European ancestry separately.ResultsAmong individuals of European genetic ancestry, PRS for breast, colon, melanoma, and prostate were significantly associated with their respective cancers (OR 1.25-1.47). Among individuals of African genetic ancestry, PRS for breast, colon, and prostate were significantly associated with their respective cancers. The AUC of a model comprised of age, sex, and principal components was 0.617–0.709 and increased by 1-4% with the PRS in individuals of European genetic ancestry. In individuals of African genetic ancestry, AUC was overall higher in the model without PRS (0.740-0.811) but increased < 1% with the PRS in the majority of cancers.ConclusionPRS constructed from SNPs moderately increased discriminatory ability for cancer status in individuals of European but not African ancestry. Further large-scale studies are needed to identify ancestry-specific genetic factors in non-White populations to incorporate PRS into cancer risk assessment.
Contact tracing indicators for COVID-19: rapid scoping review and conceptual framework
Authors: Vogt F , Kurup K , Mussleman P , Habrun C , Crowe M , Woodward A , Jaramillo-Gutierrez G , Kaldor J , Vong S , Del Rio Vilas VJ 
Published: May 2021

AbstractBackgroundContact tracing is one of the key interventions in response to the COVID-19 pandemic but its implementation varies widely across countries. There is little guidance on how to monitor contact tracing performance, and no systematic overview of indicators to assess contact tracing systems or conceptual framework for such indicators exists to date.MethodsWe conducted a rapid scoping review using a systematic literature search strategy in the peer-reviewed and grey literature as well as open source online documents. We developed a conceptual framework to map indicators by type (input, process, output, outcome, impact) and thematic area (human resources, financial resources, case investigation, contact identification, contact testing, contact follow up, case isolation, contact quarantine, transmission chain interruption, incidence reduction).ResultsWe identified a total of 153 contact tracing indicators from 1,555 peer-reviewed studies, 894 studies from grey literature sources, and 15 sources from internet searches. Two-thirds of indicators were process indicators (102; 67%), while 48 (31%) indicators were output indicators. Only three (2%) indicators were input indicators. Indicators covered seven out of ten conceptualized thematic areas, with more than half being related to either case investigation (37; 24%) or contact identification (44; 29%). There were no indicators for the input area “financial resources”, the outcome area “transmission chain interruption”, and the impact area “incidence reduction”.ConclusionsAlmost all identified indicators were either process or output indicators focusing on case investigation, contact identification, case isolation or contact quarantine. We identified important gaps in input, outcome and impact indicators, which constrains evidence-based assessment of contact tracing systems. A universally agreed set of indicators is needed to allow for cross-system comparisons and to improve the performance of contact tracing systems.