bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to High-Intensity Interval Training in Cardiac Rehabilitation
Authors: Taylor Jenna L. , Holland David J. , Keating Shelley E. , Bonikowske Amanda R. , Coombes Jeff S. 
Published: March 2021

Purpose:
High-intensity interval training (HIIT) is gaining popularity as a training approach for patients attending cardiac rehabilitation (CR). While the literature has focused on the efficacy of HIIT for improving cardiorespiratory fitness (CRF), particularly when compared with moderate intensity exercise, less emphasis has been placed on adherence to HIIT. The aim of this review was to summarize the current literature regarding adherence to HIIT in CR patients with coronary artery disease.

Review Methods:
A review identified 36 studies investigating HIIT in CR patients with coronary artery disease. Methods and data were extracted for exercise or training adherence (to attendance, intensity, and duration), feasibility of protocols, and CRF. The review summarizes reporting of adherence; adherence to HIIT and comparator/s; the influence of adherence on changes in CRF; and feasibility of HIIT.

Summary:
Adherence to the attendance of HIIT sessions was high and comparable with moderate-intensity exercise. However, adherence to the intensity and duration of HIIT was variable and underreported, which has implications for determining the treatment effect of the exercise interventions being compared. Furthermore, additional research is needed to investigate the utility of home-based HIIT and long-term adherence to HIIT following supervised programs. This review provides recommendations for researchers in the measurement and reporting of adherence to HIIT and other exercise interventions to facilitate a sufficient and consistent approach for future studies. This article also highlights strategies for clinicians to improve adherence, feasibility, and enjoyment of HIIT for their patients.
Cryoablation as Second-line Therapy for Fibroadipose Vascular Anomaly
Authors: Kaufman Claire , Frodsham Aaron , Arnold Ryan 
Published: March 2021

Purpose:
Fibroadipose vascular anomaly (FAVA) is a recently described intramuscular vascular anomaly that replaces normal skeletal muscle with fibrofatty proliferation and phlebectasia causing pain and contractures. Cryoablation has recently emerged as a means of treating FAVA with favorable outcomes. The purpose of our study was to examine our FAVA patients with failed prior interventions who underwent cryoablation as second-line treatment.

Methods:
A retrospective review was performed of all cases of cryoablation for FAVA (diagnosed on imaging or biopsy) who had undergone prior treatment from October 2014 to October 2020 at the adult and children’s hospital. Preprocedure, intraprocedural, and, when available, follow-up imaging was reviewed. Electronic medical record and imaging review was performed to determine demographics, indication, prior treatments both interventional and surgical, symptoms, and clinical response.

Results:
There were 9 patients with 11 ablation procedures; 8/9 patients had decrease in pain. One patient with diffuse FAVA had worsening pain after ablation and was subsequently treated with sirolimus.

Conclusions:
FAVA can be difficult to treat with traditional methods such as sclerotherapy or surgical resection. Cryoablation has recently emerged as a promising treatment. Our experience suggests FAVA with failed prior interventions may respond favorably to cryoablation.
Elevated T cell repertoire diversity is associated with progression of lung squamous cell premalignant lesions
Authors: Maoz Asaf , Merenstein Carter , Koga Yusuke , Potter Austin , Gower Adam C. , Liu Gang , Zhang Sherry , Liu Hanqiao , Stevenson Christopher , Spira Avrum , Reid Mary E. , Campbell Joshua D. , Mazzilli Sarah A. , Lenburg Marc E. , Beane Jennifer E. 
Published: March 2021

AbstractObjectiveThe immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features.MethodsEndobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor (TRUST) tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (i.e., found in one patient only) and public (i.e., found in two or more patients) TCRs was quantified and the CDR3 sequences were compared to those found in curated databases with known antigen specificities.ResultsWe detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T-cell mediated immune activation (Spearman’s rho −0.34, p < 0.001) associated with PML outcome.Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3,396 (8.6%) found in more than one sample and 1,057 (2.7%) found in two or more patients (i.e. public), however, when compared to a public database of CDR3 sequences, 4,543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among Public TCRs (p < 0.001).ConclusionsDecreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.
Sequence Analysis of 20,453 SARS-CoV-2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern
Authors: Long S. Wesley , Olsen Randall J. , Christensen Paul A. , Subedi Sishir , Olson Robert , Davis James J. , Saavedra Matthew Ojeda , Yerramilli Prasanti , Pruitt Layne , Reppond Kristina , Shyer Madison N. , Cambric Jessica , Finkelstein Ilya J. , Gollihar Jimmy , Musser James M. 
Published: March 2021

[Abstract]Since the beginning of the SARS-CoV-2 pandemic, there has been international concern about the emergence of virus variants with mutations that increase transmissibility, enhance escape from the human immune response, or otherwise alter biologically important phenotypes. In late 2020, several “variants of concern” emerged globally, including the UK variant (B.1.1.7), South Africa variant (B.1.351), Brazil variants (P.1 and P.2), and two related California “variants of interest” (B.1.429 and B.1.427). These variants are believed to have enhanced transmissibility capacity. For the South Africa and Brazil variants, there is evidence that mutations in spike protein permit it to escape from some vaccines and therapeutic monoclonal antibodies. Based on our extensive genome sequencing program involving 20,453 virus specimens from COVID-19 patients dating from March 2020, we report identification of all important SARS-CoV-2 variants among Houston Methodist Hospital patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency in the population, they are geographically widespread. Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination. This information is critical for medical and public health efforts to effectively address and mitigate this global crisis.
Introductions and evolutions of SARS-CoV-2 strains in Japan
Authors: Tokumasu Reitaro , Weeraratne Dilhan , Snowdon Jane , Parida Laxmi , Kudo Michiharu , Koyama Takahiko 
Published: March 2021

AbstractCOVID-19 caused by SARS-CoV-2 was first identified in Japan on January 15th, 2020, soon after the pandemic originated in Wuhan, China. Subsequently, Japan experienced three distinct waves of the outbreak in the span of a year and has been attributed to new exogenous strains and evolving existing strains. Japan engaged very early on in tracking different COVID-19 strains and have sequenced approximately 5% of all confirmed cases. While Japan has enforced stringent airport surveillance on cross-border travelers and returnees, some carriers appear to have advanced through the quarantine stations undetected. In this study 30493 genomes sampled in Japan were analyzed to understand the strains, heterogeneity and temporal evolution of different SARS-CoV-2 strains. We identified 12 discrete strains with a substantial number of cases with most strains possessing the spike (S) D614G and nucleocapsid (N) 203_204delinsKR mutations. 155 distinct strains have been introduced into Japan and 39 of them were introduced after strict quarantine policy was implemented. In particular, the B.1.1.7 strain, that emerged in the United Kingdom (UK) in September 2020, has been circulating in Japan since late 2020 after eluding cross-border quarantine stations. Similarly, the B.1.351 strain dubbed the South African variant, P.1 Brazilian strain and R.1 strain with the spike E484K mutation have been detected in Japan. At least 14 exogenous B.1.1.7 sub-strains have been independently introduced in Japan as of late March 2021, and these strains carry mutations that give selective advantage including N501Y, H69_V70del, and E484K that confer increased transmissibility, reduced efficacy to vaccines and possible increased virulence. Furthermore, various strains, which harbor multiple variants in the PCR primers and the probe developed by National Institute of Infectious Disease (NIID), are emerging. It is imperative that the quarantine policy be revised, cross-border surveillance reinforced, and new public health measures implemented to mitigate further transmission of this deadly disease and to identify strains that may engender resistance to vaccines.
Novel polygenic risk score links depression-related cortical transcriptomic changes to brain morphology and symptom severity
Authors: Miles Amy E , Dos Santos Fernanda C , Byrne Enda M , Renteria Miguel E , McIntosh Andrew M , Adams Mark J , Pistis Giorgio , Castelao Enrique , Preisig Martin , Baune Bernhard T , Schubert K Oliver , Lewis Cathryn M , Jones Lisa A , Jones Ian , Uher Rudolf , Smoller Jordan W , Perlis Roy H , Levinson Douglas F , Potash James B , Weissman Myrna M , Shi Jianxin , Lewis Glyn , Penninx Brenda WJH , Boomsma Dorret I , Hamilton Steven P ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sibille Etienne , Hariri Ahmad R , Nikolova Yuliya S 
Published: March 2021

ABSTRACTOur group developed a transcriptome-based polygenic risk score (T-PRS) that uses common genetic variants to capture ‘depression-like’ shifts in cortical gene expression. Here, we mapped T-PRS onto diagnosis and symptom severity in major depressive disorder (MDD) cases and controls from the Psychiatric Genomics Consortium (PGC). To evaluate potential mechanisms, we further mapped T-PRS onto discrete measures of brain morphology and broad depression risk in healthy young adults. Genetic, self-report, and/or neuroimaging data were available in 29,340 PGC participants (59% women; 12,923 MDD cases, 16,417 controls) and 482 participants in the Duke Neurogenetics Study (DNS: 53% women; aged 19.8±1.2 years). T-PRS was computed from SNP data using PrediXcan to impute cortical expression levels of MDD-related genes from a previous post-mortem transcriptome meta-analysis. Sex-specific regressions were used to test effects of T-PRS on depression diagnosis, symptom severity, and Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index in the PGC and DNS samples, respectively. T-PRS did not predict depression diagnosis (OR=1.007, 95%CI=[0.997-1.018]); however, it correlated with symptom severity in men (rho=0.175, p=7.957×10−4) in one large PGC cohort (N=762, 48% men). In DNS, T-PRS was associated with smaller amygdala volume in women (β=-0.186, t=-3.478, p=.001) and less prefrontal gyrification (max≤-2.970, p≤.006) in both sexes. In men, prefrontal gyrification mediated an indirect effect of T-PRS on broad depression risk (b=.005, p=.029), indexed using self-reported family history of depression. Depression-like shifts in cortical gene expression predict symptom severity in men and may contribute to disease vulnerability through their effect on cortical gyrification.
Evaluating a first fully automated interview grounded in Multiple Mini Interview (MMI) methodology: results from a feasibility study
Authors: Callwood Alison , Gillam Lee , Christidis Angelos , Doulton Jia , Harris Jenny , Coleman Marianne , Kubacki Angela , Tiffin Paul , Roberts Karen , Tarmey Drew , Dalton Doris , Valentin Virginia 
Published: March 2021

AbstractObjectivesGlobal, Covid-driven restrictions around face-to-face interviews for healthcare student selection have forced admissions staff to rapidly adopt adapted online systems before supporting evidence is available. We have developed, what we believe is, the first fully automated interview grounded in Multiple Mini-Interview (MMI) methodology. This study aimed to explore test re-test reliability, acceptability and usability of the system.Design, setting and participantsmixed-methods feasibility study in Physician Associate (PA) programmes from two UK and one US university during 2019 - 2020.Primary, secondary outcomesFeasibility measures (test retest reliability acceptability and usability) were assessed using intra-class correlation (ICC), descriptive statistics, thematic and content analysis.MethodsVolunteers took (T1), then repeated (T2), the automated MMI, with a seven-day interval (+/− 2) then completed an evaluation questionnaire. Admissions staff participated in focus group discussions.ResultsSixty-two students and seven admission staff participated; 34 students and four staff from UK and 28 students and three staff from US universities.Good-excellent test-retest reliability was observed with T1 and T2 ICC between 0.62-0.81 (p<0.001) when assessed by individual total scores (range 80.6-119), station total scores 0.6-0.91, p<0.005, individual site (all ICC≥ 0.76 p<0.001) and mean test retest across sites 0.82 p<0.001 (95% CI 0.7-0.9).Admissions staff reported potential to reduce resource costs and bias through a more objective screening tool for pre-selection or to replace some MMI stations in a ‘hybrid model’. Maintaining human interaction through ‘touch points’ was considered essential.Users positively evaluated the system, stating it was intuitive with an accessible interface. Concepts chosen for dynamic probing needed to be appropriately tailored.ConclusionThese preliminary findings suggest that the system is reliable, generating consistent scores for candidates and is acceptable to end-users provided human touchpoints are maintained. Thus, there is evidence for the potential of such an automated system to augment healthcare student selection processes.
Revisiting Bias in Odds Ratios
Authors: Foppa Ivo M , Dahlgren Fredrick S 
Published: March 2021

AbstractRatio measures of effect, such as the odds ratio (OR), are consistent, but the presumption of their unbiasedness is founded on a false premise: The equality of the expected value of a ratio and the ratio of expected values. We show that the invalidity of this assumptions is an important source of empirical bias in ratio measures of effect, which is due to properties of the expectation of ratios of count random variables. We investigate ORs (unconfounded, no effect modification), proposing a correction that leads to “almost unbiased” estimates. We also explore ORs with covariates. We find substantial bias in OR estimates for smaller sample sizes, which can be corrected by the proposed method. Bias correction is more elusive for adjusted analyses. The notion of unbiasedness of OR for the effect of interest for smaller sample sizes is challenged.
Vaccine hesitancy and reasons for refusing the COVID-19 vaccination among the U.S. public: A cross-sectional survey
Authors: Raja Ali S. , Niforatos Joshua D. , Anaya Nancy , Graterol Joseph , Rodriguez Robert M. 
Published: March 2021

AbstractImportanceAlthough widespread vaccination will be the most important cornerstone of the public health response to the COVID-19 pandemic, a critical question remains as to how much of the United States population will accept it.ObjectiveDetermine: 1) rate of COVID-19 vaccine hesitancy in the United States public, 2) patient characteristics associated with hesitancy, 3) reasons for hesitancy, 4) healthcare sites where vaccine acceptors would prefer to be vaccinated.Design43-question cross-sectional survey conducted November 17-18, 2020, distributed on Amazon Mechanical Turk, an online labor marketplace where individuals receive a nominal fee (here, $1.80) for anonymously completing tasks.Eligible ParticipantsUnited States residents 18-88 years of age, excluding healthcare workers. A total 1,756 volunteer respondents completed the survey (median age 38 years, 53% female).Main Outcome MeasureMultivariable logistic regression modeled the primary outcome of COVID-19 vaccine hesitancy (defined as non-acceptance or being unsure about acceptance of the COVID-19 vaccine) with respondent characteristics.ResultsA total 663 respondents (37.8%) were COVID-19 vaccine hesitant (374 [21.3%] non-acceptors and 289 [16.5%] unsure about accepting). Vaccine hesitancy was associated with not receiving influenza vaccination in the past 5 years (odds ratio [OR] 4.07, 95% confidence interval [CI] 3.26-5.07, p<0.01), female gender (OR 2.12, 95%CI 1.70-2.65, p<0.01), Black race (OR 1.54, 95%CI 1.05-2.26, p=0.03), having a high school education or less (OR 1.46, 95%CI 1.03-2.07, p=0.03), and Republican party affiliation (OR 2.41, 95%CI 1.88-3.10, p<0.01). Primary reasons for hesitancy were concerns about side effects, need for more information, and doubts about vaccine efficacy. Preferred sites for vaccination for acceptors were primary doctors’ offices/clinics, pharmacies, and dedicated vaccination locations.ConclusionsIn this recent national survey, over one-third of respondents were COVID-19 vaccine hesitant. To increase vaccine acceptance, public health interventions should target vaccine hesitant populations with messaging that addresses their concerns about safety and efficacy.
Development of a Metastatic Uveal Melanoma Prognostic risk Score (MUMPS) for use in patients receiving immune checkpoint inhibitors
Authors: Kelly Deirdre , Rose April A. N. , Muniz Thiago Pimentel , Hogg David , Butler Marcus O. , Saibil Samuel D. , King Ian , Kamil Zaid Saeed , Ghazarian Danny , Ross Kendra , Iafolla Marco , Araujo Daniel V. , Waldron John , Laperriere Normand , Krema Hatem , Spreafico Anna 
Published: March 2021

AbstractBackgroundMetastatic uveal melanoma (mUM) is a rare disease for which no systemic therapy has demonstrated overall survival (OS) benefit. There are no robust data on prognostic factors for OS in patients with mUM treated with immune checkpoint inhibitors (ICI).Retrospective and non-randomized prospective studies have reported response rates of 0-37% for anti-PD1/L1 +/-anti-CTLA4 ICI in mUM, indicating a potential benefit only in a subset of patients. This study evaluates the characteristics associated with ICI benefit in patients with mUM.MethodsWe performed a single-center retrospective cohort study of patients with mUM who received anti-PD1/L1 +/-anti-CTLA4 ICI between 2014–2019. Clinical and genomic characteristics were collected from chart review. Treatment response and clinical progression were determined by physician assessment. Multivariable Cox regression models and Kaplan-Meier log-rank tests were used to assess differences in clinical progression-free survival (cPFS) and OS between groups and to identify clinical variables associated with ICI outcomes.ResultsWe identified 71 mUM patients who received 75 lines of ICI therapy. Of these, 54 received anti-PD1/L1 alone, and 21 received anti-PD1/L1 + anti-CTLA4. Patient characteristics were: 53% female, 48% were 65 or older, 72% received one or fewer lines of prior therapy. Within our cohort, 53% of patients had developed stage IV disease < 2 years after their initial diagnosis. Bone metastases were present in 12% of patients. For the entire cohort, the median cPFS was 2.7 months and median OS was 10.0 months. In multivariable analyses for both cPFS and OS, the following variables were associated with good prognosis: ≥ 2yrs from initial diagnosis to stage IV (n=25), LDH <1.5xULN (n=45), and absence of bone metastases (n=66). We developed a Metastatic Uveal Melanoma Prognostic risk Score (MUMPS). Patients were divided into 3 MUMPS risk groups based on the number of the above-mentioned prognostic variables: Poor risk (0-1), Intermediate risk (2) and Good risk (3). Good risk patients experienced longer cPFS (6.0 months) and OS (34.5 months) than patients with intermediate (2.3 months cPFS, 9.4 months OS) and poor risk disease (1.8 months cPFS, 3.9 months OS); P<0.0001.ConclusionWe developed a MUMPS risk score, based on retrospective data, that is comprised of 3 readily available clinical variables (time to stage IV diagnosis, presence of bone metastases, and LDH). This MUMPS risk score has potential prognostic value. Further validation in independent datasets is warranted to determine the role of this MUMPS risk score in selecting ICI treatment management for mUM.