bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer
Authors: Vuky Jacqueline , Balar Arjun V. , Castellano Daniel , O’Donnell Peter H. , Grivas Petros , Bellmunt Joaquim , Powles Thomas , Bajorin Dean , Hahn Noah M. , Savage Mary J. , Fang Xiao , Godwin James Luke , Frenkl Tara L. , Homet Moreno Blanca , de Wit Ronald , Plimack Elizabeth R. 
Published: June 2020

PURPOSE The phase II single-arm KEYNOTE-052 study evaluated the efficacy and safety of first-line pembrolizumab for patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC). PATIENTS AND METHODS Three hundred seventy patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months. Positive tumor programmed death ligand 1 (PD-L1) expression was defined as combined positive score (CPS) ≥ 10. Response was assessed by independent central review every 9 weeks per RECIST v1.1. The primary end point was objective response rate (ORR). RESULTS At data cutoff (September 26, 2018), the minimum follow-up was 2 years since the last patient enrolled. ORR was 28.6% (95% CI, 24.1% to 33.5%); 33 patients (8.9%) and 73 patients (19.7%) achieved complete and partial response, respectively. The median duration of response was 30.1 months (95% CI, 18.1 months to not reached [NR]); responses lasted ≥ 12 and ≥ 24 months in 67% and 52% of patients, respectively. Forty patients with complete or partial response completed 2 years of study treatment, and 32 had ongoing response at completion. Median overall survival (OS) was 11.3 months (95% CI, 9.7 to 13.1 months), and 12- and 24-month OS rates were 46.9% and 31.2%, respectively. In patients with CPS ≥ 10, ORR was 47.3% (95% CI, 37.7% to 57.0%) and median OS was 18.5 months (95% CI, 12.2 to 28.5 months). In patients with lymph node–only disease, ORR was 49.0% (95% CI, 34.8% to 63.4%), and median OS was 27.0 months (12.4 months to NR). There were no new safety signals. CONCLUSION First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced UC and is associated with prolonged OS, particularly with PD-L1 CPS ≥ 10 and lymph node–only disease.
Evaluation of a Virtual Learning Collaborative to Integrate Palliative Care Into Routine Oncology Practice
Authors: Kamal Arif H. , Bossley Heidi , Blum Ronald , Berman Amy J. , von Gunten Charles , Von Roenn Jamie 
Published: June 2020

PURPOSE: The integration of palliative care into usual oncology care is a best practice, but implementation can be challenging. METHODS: We convened a virtual learning collaborative (VLC) of oncology practices with a focus on integrating palliative care. The entire program was virtual, with teams meeting via online Webinar and conference call and accessing content via an online portal. Because of the need to pause and retool after the first 5 months, the VLC evolved into 2 phases, with feedback after the first phase informing the second. We primarily evaluated the reaction of participants and project team members after the completion of the VLC using 2 quantitative surveys (after each phase) and semistructured interviews with participants. RESULTS: A total of 24 oncology practices entered the VLC. Evaluation after each of 2 phases was conducted. For the first evaluation, 67% of respondents agreed a quality improvement coach was helpful to complete the program; 61% agreed a palliative care expert was helpful. The most common reasons for withdrawal involved organizational and VLC factors. Organizational factors included: time constraints, personnel changes (turnover), loss of the champion, and lack of team engagement. Twenty-two active participants and 8 former participants completed the second survey. Of those, 79% agreed the experience with the VLC was valuable, and 74% agreed the virtual delivery mode was useful. We identified 3 themes to drive future improvements related to structure, engagement, and content. CONCLUSION: VLCs are a potential mechanism to disseminate information and facilitate learning in oncology. Further study of program characteristics that promote acceptance of VLCs are needed.
Determinants of Bone Material Strength and Cortical Porosity in Patients with Type 2 Diabetes Mellitus
Authors: Samakkarnthai Parinya , Sfeir Jad G , Atkinson Elizabeth J , Achenbach Sara J , Wennberg Paul W , Dyck Peter J , Tweed Amanda J , Volkman Tammie L , Amin Shreyasee , Farr Joshua N , Vella Adrian , Drake Matthew T , Khosla Sundeep 
Published: June 2020

Abstract

Context
Reduced bone material strength index (BMSi) and increased cortical porosity (CtPo) have emerged as potentially contributing to fracture risk in type 2 diabetes mellitus (T2DM) patients.

Objective
To determine whether BMSi or CtPo are related to other diabetic complications.

Design
Cross-sectional observational study.

Setting
Subjects recruited from a random sample of southeast Minnesota residents.

Participants
A total of 171 T2DM patients (mean age, 68.8 years) and 108 age-matched nondiabetic controls (mean age, 67.3 years).

Main Measures
Bone material strength index was measured using microindentation, skin advanced glycation end-products (AGEs) measured using autofluorescence, high-resolution peripheral quantitative computed tomography at the distal radius and tibia, assessment of diabetic microvascular complications including urine microalbuminuria, retinopathy, neuropathy, and vascular disease (ankle brachial index and transcutaneous oxygen tension [TcPO2]). All analyses were adjusted for age, sex, and body mass index.

Results
Skin AGEs were negatively correlated with the BMSi in both T2DM (r = -0.30, P &lt; 0.001) and control (r = -0.23, P = 0.020) subjects. In relating diabetic complications to CtPo, we found that T2DM patients with clinically significant peripheral vascular disease (TcPO2 ≤ 40 mm Hg) had higher (+21.0%, P = 0.031) CtPo at the distal tibia as compared to controls; in these subjects, CtPo was negatively correlated with TcPO2 at both the distal tibia (r = -0.39, P = 0.041) and radius (r = -0.41, P = 0.029).

Conclusions
Our findings demonstrate that bone material properties are related to AGE accumulation regardless of diabetes status, while CtPo in T2DM patients is linked to TcPO2, a measure of microvascular blood flow.
Vascular Protection by Exercise in Obesity: Inflammasome-associated Mechanisms
Authors: LEE JONGHAE , HONG JUNYOUNG , UMETANI MICHIHISA , LAVOY EMILY C. , KIM JONG-HEE , PARK YOONJUNG 
Published: June 2020

ABSTRACT

Purpose
The nodlike receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical player in vascular pathology as it regulates caspase-1-mediated interleukin (IL)-1β processing. Physical activity ameliorates obesity-induced inflammation and vascular dysfunction, but the mechanisms responsible for these positive changes are incompletely understood. Here, the protective effect of physical activity on the inflammasome-associated vascular dysfunction in obesity and its putative mechanisms were investigated.

Methods
Mice were fed a control low-fat diet (LFD) or a high-fat diet (HFD; 45% of calories from fat) and provided with running wheel access (LF-RUN or HF-RUN) or denied wheel access for our sedentary condition (LF-SED or HF-SED). The NLRP3 inflammasome-associated pathway, including NLRP3, caspase-1, and IL-1β, in mice aorta was examined by RT-qPCR and FLICA and DAB staining. The protein expression of zonula occluden-1 (ZO-1), ZO-2, adiponectin (APN), and adiponectin receptor 1 (AdipoR1) in aortic endothelial cells was determined by immunofluorescence double staining. Intracellular reactive oxidative stress and nitric oxide (NO) production were monitored with fluorescence probes, dihydroethidium, and diaminofluorecein.

Results
HFD increased caspase-1 and IL-1β at mRNA and protein levels in endothelial cells of the aorta, and this was attenuated by voluntary running. HFD decreased ZO-1 and ZO-2 expression and reduced APN and AdipoR1 signaling; these were restored by running. The elevated intracellular superoxide (O2
.-) production observed in HF-SED was ameliorated in HF-RUN. Finally, HF-RUN improved NO production in the aorta compared with HF-SED.

Conclusions
Our findings suggest that voluntary running ameliorates mechanisms associated with vascular dysfunction by suppressing NLRP3 inflammasome, improving NO production, and reducing oxidative stress. Such benefits of physical activity may be, at least in part, associated with APN–AdipoR1 signaling and tight junction protein expression.
Elevated Perceived Exertion in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis
Authors: BARHORST ELLEN E. , ANDRAE WILLIAM E. , RAYNE TESSA J. , FALVO MICHAEL J. , COOK DANE B. , LINDHEIMER JACOB B. 
Published: June 2020

ABSTRACT

Purpose
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating illnesses primarily characterized by chronic symptoms of fatigue and musculoskeletal pain, respectively. Some investigators have observed an elevated sense of effort in these patient groups; however, this effect has not been substantiated via quantitative review. As such, we conducted a meta-analysis of RPE responses to aerobic exercise in ME/CFS and FM compared with healthy adults.

Methods
Case–control studies involving adults with ME/CFS or FM that measured RPE and heart rate responses to acute aerobic exercise were included. Data sources included PubMed, Scopus/Embase, CINAHL, CENTRAL, and Google Scholar. Risk of bias was assessed by evaluating each study’s description of participant characteristics, matching procedures, and administration of RPE scales. Hedges’ d effect sizes for RPE were calculated and aggregated using random-effects models, and potential moderators were explored with meta-regression analysis.

Results
Forty-one effects were extracted from 37 studies involving 1016 patients and 686 healthy controls. We observed a large (Hedges’ d = 0.85, 95% confidence interval = 0.62–1.08) effect indicating higher RPE in patients than controls. The mean effect size was significantly moderated (P < 0.001, R
2 = 0.38) by whether RPE data were analyzed at a peak or submaximal intensity (b = 0.60, z = 4.6, P < 0.001) and the type of patient group that was studied (b = 0.25, z = 2.08, P = 0.04).

Conclusions
People with ME/CFS and FM perceive aerobic exercise as more effortful than healthy adults, but the exact causes are unclear. The large magnitude of this effect merits further exploration of underlying mechanisms that could provide insight into the pathophysiology of ME/CFS and FM or the broader debate about the nature of central and/or peripheral signals that influence RPE.
Development of Concise Physical Performance Test Batteries in Young Athletes
Authors: LENTZ TREVOR A. , MAGILL JOHN , MYERS HEATHER , PIETROSIMONE LAURA S. , REINKE EMILY K. , MESSER MICHAEL , RIBOH JONATHAN C. 
Published: June 2020

ABSTRACT

Purpose
This study aimed 1) to define the principal components of physical function assessed by 10 common lower extremity physical performance tests and 2) to derive a reduced-item set of physical performance tests that efficiently and accurately measures raw performance and limb symmetry on each underlying component in pediatric and adolescent athletes.

Methods
This study included healthy, uninjured volunteers (n = 100) between the ages 6 and 18 yr (mean age = 11.7 ± 3.6 yr; 52 females). Subjects performed the stork balance, stork balance on BOSU® Balance Trainer, single leg squat (SLS), SLS on BOSU, clockwise and counterclockwise quadrant single leg hop (SLH), forward SLH, timed SLH, triple crossover SLH, and lower quarter Y-Balance Test™. Item reduction was performed using principal components analysis (PCA). We developed separate principal components analysis for average raw performance and side-to-side limb symmetry, with secondary analyses to evaluate consistency of results by age and sex.

Results
We identified two components for average raw performance (accounting for 65.2% of the variance in total test battery) with a reduced-item set composed of five tests, and four components for limb symmetry (accounting for 62.9% of the variance in total test battery) with a reduced-item set of seven tests. The most parsimonious test suitable for screening both average raw performance and limb symmetry would consist of five tests (stork balance on BOSU, SLS on BOSU, forward SLH, timed SLH, and lower quarter Y-Balance Test™). Age- and sex-specific test batteries may be warranted.

Conclusion
Comprehensive screening for lower extremity average raw performance and limb symmetry is possible with short physical performance test batteries.
Validation and Cardiorespiratory Response of the 1-Min Sit-to-Stand Test in Interstitial Lung Disease
Authors: TREMBLAY LABRECQUE PIERRE-FRANÇOIS , HARVEY Jany , NADREAU ÉRIC , MALTAIS FRANÇOIS , DION GENEVIÈVE , SAEY DIDIER 
Published: June 2020

ABSTRACTPurposeTo assess the 1-min sit-to-stand test (1STS) test–retest reliability and construct validity and its associated cardiorespiratory response in comparison to the 6-min walk test (6MWT) and symptom-limited cycling cardiopulmonary exercise test (CPET) in people with interstitial lung disease (ILD).MethodsFifteen participants with ILD performed two 1STS tests, a 6MWT and a CPET. The three tests were administered on three separate visits, and cardiorespiratory parameters were continuously recorded during the tests.ResultsThe number of repetitions during both 1STS tests was 22 ± 4 and 22 ± 4 (mean difference of 0.53 ± 2.00 repetitions,P= 0.32) with an intraclass correlation of 0.937 (95% confidence interval, 0.811–0.979]) and a minimal detectable change of 2.9 repetitions. The number of 1STS repetitions was highly correlated with the 6MWT distance (r= 0.823,P< 0.001) and with the peak cycling power output expressed in % predicted values (r= 0.706,P< 0.003). Oxygen consumption (V˙O2) peak during the 1STS reached 83% and 78% of V˙O2peak during 6MWT and CPET, respectively. Peak 1STS HR, minute ventilation (V˙E,), V˙O2values, as well as nadir SpO2were achieved during the recovery phase of the test, whereas peak 6MWT and CPET HR,V˙E, V˙O2and nadir SpO2always occurred at the end of the test. The three tests elicited a similar fall in SpO2ranging between 8% and 12%. Symptom scores after the 1STS were similar to those seen at the end of the 6MWT but lower than those of CPET.ConclusionsThe 1STS showed excellent test–retest reliability in patients with ILD in whom it elicited a substantial, but submaximal cardiorespiratory response. Our data also support the construct validity of the 1STS to assess functional exercise capacity in patients with ILD and to detect exercise-induced O2desaturation.
Modeling the Recovery of W′ in the Moderate to Heavy Exercise Intensity Domain
Authors: SREEDHARA VIJAY SARTHY M. , ASHTIANI FARAZ , MOCKO GREGORY M. , VAHIDI ARDALAN , HUTCHISON RANDOLPH E. 
Published: June 2020

ABSTRACT

Purpose
This study (i) investigates the effect of recovery power (Prec) and duration (t
rec) on the recovery of the curvature constant (W′) of the power–duration relationship, (ii) compares the experimentally measured W′ balance to that predicted (W′
bal) by two models (SK2 and BAR), and (iii) presents a case of real-time performance optimization using the critical power (CP) concept.

Methods
Seven competitive amateur cyclists performed a ramp test to determine their V˙O2peak and gas exchange threshold, two to four 3-min all-out tests to determine CP and W′, and nine intermittent cycling tests to investigate W′ recovery. The intermittent cycling tests involved a 2-min constant work-rate interval above CP, followed by a constant work-rate recovery interval below CP (Prec and t
rec were varied), followed by a 3-min all-out interval.

Results
There was a significant two-way interaction between Prec and t
rec on W′ recovery, P = 0.004 (η
2 = 0.52). Simple main effects were present only with respect to Prec at each t
rec. The actual W′ balance at the end of the recovery interval was less than the W′
bal predicted by both SK2 (P = 0.035) and BAR (P = 0.015) models. The optimal strategy derived from the subject-specific recovery model reduced the race time by 55 s as compared with the self-strategy.

Conclusions
This study has shown that in a recovery interval, Prec has a greater influence than t
rec on W′ recovery. The overprediction of W′
bal from SK2 and BAR suggests the need for individualized recovery parameters or models for sub-CP exercise. Finally, the optimal strategy results provide encouraging signs for real-time, model-based performance optimization.
Development of a Cadence-based Metabolic Equation for Walking
Authors: MOORE CHRISTOPHER C. , AGUIAR ELROY J. , DUCHARME SCOTT W. , TUDOR-LOCKE CATRINE 
Published: June 2020

ABSTRACT

Purpose
This study aimed to develop cadence-based metabolic equations (CME) for predicting the intensity of level walking and evaluate these CME against the widely adopted American College of Sports Medicine (ACSM) Metabolic Equation, which predicts walking intensity from speed and grade.

Methods
Two hundred and thirty-five adults (21–84 yr of age) completed 5-min level treadmill walking bouts between 0.22 and 2.24 m·s−1, increasing by 0.22 m·s−1 for each bout. Cadence (in steps per minute) was derived by dividing directly observed steps by bout duration. Intensity (oxygen uptake; in milliliters per kilogram per minute) was measured using indirect calorimetry. A simple CME was developed by fitting a least-squares regression to the cadence–intensity relationship, and a full CME was developed through best subsets regression with candidate predictors of age, sex, height, leg length, body mass, body mass index (BMI), and percent body fat. Predictive accuracy of each CME and the ACSM metabolic equation was evaluated at normal (0.89–1.56 m·s−1) and all (0.22–2.24 m·s−1) walking speeds through k-fold cross-validation and converted to METs (1 MET = 3.5 mL·kg−1·min−1).

Results
On average, the simple CME predicted intensity within ~1.8 mL·kg−1·min−1 (~0.5 METs) at normal walking speeds and with negligible (<0.01 METs) bias. Including age, leg length, and BMI in the full CME marginally improved predictive accuracy (≤0.36 mL·kg−1·min−1 [≤0.1 METs]), but may account for larger (up to 2.5 mL·kg−1·min−1 [0.72 MET]) deviations in the cadence–intensity relationships of outliers in age, stature, and/or BMI. Both CME demonstrated 23%–35% greater accuracy and 2.2–2.8 mL·kg−1·min−1 (0.6–0.8 METs) lower bias than the ACSM metabolic equation’s speed-based predictions.

Conclusions
Although the ACSM metabolic equation incorporates a grade component and is convenient for treadmill-based applications, the CME developed herein enables accurate quantification of walking intensity using a metric that is accessible during overground walking, as is common in free-living contexts.
An Intervention for Mental Health Literacy and Resilience in Organized Sports
Authors: VELLA STEWART A. , SWANN CHRISTIAN , BATTERHAM MARIJKA , BOYDELL KATHERINE M. , ECKERMANN SIMON , FERGUSON HELEN , FOGARTY ANDREA , HURLEY DIARMUID , LIDDLE SARAH K. , LONSDALE CHRIS , MILLER ANDREW , NOETEL MICHAEL , OKELY ANTHONY D. , SANDERS TAREN , SCHWEICKLE MATTHEW J. , TELENTA JOANNE , DEANE FRANK P. 
Published: June 2020

ABSTRACT

Purpose
In this study, we tested the effectiveness of a multicomponent sports-based program aimed at promoting early intervention, help seeking, and resilience among a sample of adolescent male sport participants.

Methods
The Ahead of the Game program comprised four intervention components and a messaging campaign. Two components targeted mental health literacy, intentions to seek and provide help, and resilience among adolescent boys. A mental health literacy program for parents and a coach education program to assist in the support of athletes’ psychological needs were also included. We evaluated the program using a nonrandomized controlled trial matching two regional communities. In total, 350 sport participants (mean, 14.53 yr) were included in an intervention group, whereas 466 (mean, 14.66 yr) received usual practice in a matched control community. One hundred and eighty parents or caregivers and eight coaches also participated in the intervention components. Between-group mean differences on the primary and secondary outcomes were analyzed using linear mixed models, adjusted for clustering at club level, participant age, and socioeconomic status.

Results
Significant positive group–time interactions were found for the primary outcomes of depression and anxiety literacy, intentions to seek help from formal sources, confidence to seek mental health information, and resilience. We also found a significant positive group–time interaction for the secondary outcome of well-being. There were no group–time interactions for social distance (stigma), intentions to seek help from informal sources, implicit beliefs about adversity, perceived familial support, or psychological distress.

Conclusions
Given the high rates of sport participation worldwide and the increasing focus on mental health in this domain, translation and dissemination of the program may be warranted after replication.
High-Intensity Shoulder Abduction Exercise in Subacromial Pain Syndrome
Authors: BERG OLE KRISTIAN , PAULSBERG FREDRIK , BRABANT CLARA , ARABSOLGHAR KEYVAN , RONGLAN SIGRID , BJØRNSEN NINA , TØRHAUG TOM , GRANVIKEN FREDRIK , GISMERVIK SIGMUND , HOFF JAN 
Published: June 2020

ABSTRACT
Subacromial pain syndrome (SAPS) defined as pain of nontraumatic origin localized around the acromion, is a debilitating, common, and often chronic condition. Among many proposed underlying causes of SAPS, hypoperfusion and hypoxic conditions in and around the tendons may be an intrinsic cause of SAPS.

Purpose
This study aimed to determine if adding high-intensity aerobic interval training (HIIT) of the rotator cuff to usual care was feasible in SAPS and improved shoulder endurance more than usual care alone, as well as to examine the influence on shoulder pain and disability and the response of tendinous microcirculation after HIIT.

Methods
Twenty-one subjects with chronic SAPS were randomized to two groups: experimental group (EG; n = 13) receiving HIIT in addition to treatment as usual and control group (CG; n = 8) receiving treatment as usual. Before and after 8 wk of exercise therapy, endurance performance was assessed by an incremental abduction exercise of the arm to exhaustion (TTE). Pain and disability was assessed by the shoulder pain and disability index (SPADI). Contrast-enhanced ultrasound of the musculus supraspinatus and tendon was utilized to indicate tendon blood flow.

RESULTS
Endurance in the TTE test improved by an estimated 233 s more on average in EG than in CG (P = 0.001; 95% confidence interval, 102 to 363). The SPADI score was reduced 22 points more on average in EG (P = 0.017; 95% confidence interval, −40 to −5). The change from pretest to posttest was significant in EG for both TTE test and SPADI improvement (P < 0.001). EG also experienced less pain during exercise after the intervention compared with CG (P < 0.001). Contrast-enhanced ultrasound indicated an increase in tendinous blood flow in EG (P = 0.019).

Conclusions
HIIT rotator cuff exercise seems to be a feasible intervention in SAPS, increasing endurance performance more than usual care alone.