bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profoundly lower muscle mass and rate of contractile protein synthesis in boys with Duchenne muscular dystrophy
Authors: Evans William J. , Shankaran Mahalakshmi , Smith Edward C. , Morris Carl , Nyangau Edna , Bizieff Alec , Matthews Marcy , Mohamed Hussein , Hellerstein Marc 
Published: September 2021

AbstractBoys with Duchenne muscular dystrophy (DMD) experience a progressive loss of functional muscle mass, with fibrosis and lipid accumulation. Accurate evaluation of whole‐body functional muscle mass (MM) in DMD patients has not previously been possible and the rate of synthesis of muscle proteins remains unexplored. We used non‐invasive, stable isotope‐based methods from plasma and urine to measure the fractional rate of muscle protein synthesis (FSR) functional muscle mass (MM), and fat free mass (FFM) in 10 DMD (6–17 years) and 9 age‐matched healthy subjects. An oral dose of D3creatine in 70% 2H2O was administered to determine MM and FFM followed by daily 70% 2H2O to measure protein FSR. Functional MM was profoundly reduced in DMD subjects compared to controls (17% vs. 41% of body weight, P < 0.0001), particularly in older, non‐ambulant patients in whom functional MM was extraordinarily low (<13% body weight). We explored the urine proteome to measure FSR of skeletal muscle‐derived proteins. Titin, myosin light chain and gelsolin FSRs were substantially lower in DMD subjects compared to controls (27%, 11% and 40% of control, respectively, P < 0.0001) and were strongly correlated. There were no differences in muscle‐derived sarcoplasmic proteins FSRs (creatine kinase M‐type and carbonic anhydrase‐3) measured in plasma. These data demonstrate that both functional MM, body composition and muscle protein synthesis rates can be quantified non‐invasively and are markedly different between DMD and control subjects and suggest that the rate of contractile but not sarcoplasmic protein synthesis is affected by a lack of dystrophin.Key points
Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle but total body functional muscle mass or rates of muscle protein synthesis have not previously been assessed in these patients.
D3‐creatine dilution was used to measure total functional muscle mass and oral 2H2O was used to examine the rates of muscle protein synthesis non‐invasively in boys with DMD and healthy controls using urine samples.
Muscle mass was profoundly lower in DMD compared to control subjects, particularly in older, non‐ambulant patients.
The rates of contractile protein synthesis but not sarcoplasmic proteins were substantially lower in DMD.
These results may provide non‐invasive biomarkers for disease progression and therapeutic efficacy in DMD and other neuromuscular diseases.
External, Internal, Perceived Training Loads and Their Relationships in Youth Basketball Players Across Different Positions
Authors: Sansone Pierpaolo , Ceravolo Alessandro , Tessitore Antonio 
Published: September 2021

Purpose: To quantify external, internal, and perceived training loads and their relationships in youth basketball players across different playing positions. Methods: Fourteen regional-level youth male players (age: 15.2 [0.3] y) were monitored during team-based training sessions across 10 in-season weeks. The players were monitored with BioHarness-3 devices, to measure external (Impulse Load, in Newtons per second) and internal (summated-heart-rate zones [SHRZ], in arbitrary units [AU]) loads, and with the session rating of perceived exertion (sRPE, in AU) method to quantify perceived training load. Multiple linear mixed models were performed to compare training loads between playing positions (backcourt and frontcourt). Repeated-measures correlations were performed to assess the relationships between the load models, for all players and within playing positions. Results: External load (backcourt: 13,599 [2260] N·s; frontcourt: 14,934 [2173] N·s) and sRPE (backcourt: 345 [132] AU; frontcourt: 505 [158] AU) were higher in the frontcourt (P < .05, effect size: moderate), while SHRZ was similar between positions (backcourt: 239 [45] AU; frontcourt: 247 [43] AU) (P > .05; effect size: trivial). The correlations were as follows: large between the external load and SHRZ (r = .57, P < .001), moderate between SHRZ and sRPE (r = .45, P < .001), and small between the external load and sRPE (r = .26, P = .02). The correlation magnitudes were equivalent for external load–SHRZ (large) and SHRZ–sRPE (moderate) across positions, but different for the external load–sRPE correlation (small in backcourt; moderate in frontcourt). Conclusions: In youth basketball, small–large commonalities were found between the training dose (external load) and players’ responses (internal and perceived loads). Practitioners should carefully manage frontcourt players’ training loads because they accumulate greater external and perceived loads than backcourt players do.
Influence of social determinants of health and county vaccination rates on machine learning models to predict COVID-19 case growth in Tennessee
Authors: Wylezinski Lukasz S , Harris Coleman R , Heiser Cody N , Gray Jamieson D , Spurlock Charles F 
Published: September 2021

IntroductionThe SARS-CoV-2 (COVID-19) pandemic has exposed health disparities throughout the USA, particularly among racial and ethnic minorities. As a result, there is a need for data-driven approaches to pinpoint the unique constellation of clinical and social determinants of health (SDOH) risk factors that give rise to poor patient outcomes following infection in US communities.MethodsWe combined county-level COVID-19 testing data, COVID-19 vaccination rates and SDOH information in Tennessee. Between February and May 2021, we trained machine learning models on a semimonthly basis using these datasets to predict COVID-19 incidence in Tennessee counties. We then analyzed SDOH data features at each time point to rank the impact of each feature on model performance.ResultsOur results indicate that COVID-19 vaccination rates play a crucial role in determining future COVID-19 disease risk. Beginning in mid-March 2021, higher vaccination rates significantly correlated with lower COVID-19 case growth predictions. Further, as the relative importance of COVID-19 vaccination data features grew, demographic SDOH features such as age, race and ethnicity decreased while the impact of socioeconomic and environmental factors, including access to healthcare and transportation, increased.ConclusionIncorporating a data framework to track the evolving patterns of community-level SDOH risk factors could provide policy-makers with additional data resources to improve health equity and resilience to future public health emergencies.
Impact evaluation of the efficacy of different doses of vitamin D supplementation during pregnancy on pregnancy and birth outcomes: a randomised, controlled, dose comparison trial in Pakistan
Authors: Nausheen Sidrah , Habib Atif , Bhura Maria , Rizvi Arjumand , Shaheen Fariha , Begum Kehkashan , Iqbal Junaid , Ariff Shabina , Shaikh Lumaan , Raza Syed Shamim , Soofi Sajid Bashir 
Published: September 2021

BackgroundVitamin D deficiency during pregnancy is a public health problem in Pakistan and is prevalent among most women of reproductive age in the country. Vitamin D supplementation during pregnancy is suggested to prevent adverse pregnancy outcomes and vitamin D deficiency in both the mother and her newborn.MethodsWe conducted a double-blinded, randomised controlled trial in Karachi, Pakistan to evaluate the effect of different doses of vitamin D supplementation during pregnancy on biochemical markers (serum 25(OH)D, calcium, phosphorus and alkaline phosphatase) in women and neonates, and on pregnancy and birth outcomes (gestational diabetes, pre-eclampsia, low birth weight, preterm births and stillbirths).ResultsPregnant women (N=350) in their first trimester were recruited and randomised to three treatment groups of vitamin D supplementation: 4000 IU/day (group A, n=120), 2000 IU/day (group B, n=115) or 400 IU/day (group C, n=115). Women and their newborn in group A had the lowest vitamin D deficiency at endline (endline: 75.9%; neonatal: 64.9%), followed by group B (endline: 84.9%; neonatal: 73.7%) and then the control group (endline: 90.2%; neonatal: 91.8%). Vitamin D deficiency was significantly lower in group A than in group C (p=0.006) among women at endline and lower in both groups A and B than in the control group (p=0.001) in neonates. Within groups, serum 25(OH)D was significantly higher between baseline and endline in group A and between maternal baseline and neonatal levels in groups A and B. Participant serum 25(OH)D levels at the end of the trial were positively correlated with those in intervention group A (4000 IU/day) (β=4.16, 95% CI 1.6 to 6.7, p=0.002), with food group consumption (β=0.95, 95% CI 0.01 to 1.89, p=0.047) and with baseline levels of serum 25(OH)D (β=0.43, 95% CI 0.29 to 0.58, p<0.0001).ConclusionThe evidence provided in our study indicates that vitamin D supplementation of 4000 IU/day was more effective in reducing vitamin D deficiency among pregnant women and in improving serum 25(OH)D levels in mothers and their neonates compared with 2000 IU/day and 400 IU/day.Trial registration numberNCT02215213.
Knowledge, attitude and practices regarding health self-management among patients with osteogenesis imperfecta in China: an online cross-sectional survey
Authors: Lai Yongjie , Lu Wenchao , Mao Huijia , Zhang Yueyang , Ming Wai-kit , Wu Yibo 
Published: September 2021

ObjectivesAssessing the knowledge, attitude and practices (KAP) regarding health self-management among patients with osteogenesis imperfecta (OI) in China.DesignAn online cross-sectional survey.SettingA structured questionnaire was distributed online through China-Dolls Center for Rare Disorders (CCRD), a non-governmental charity in China.ParticipantsParticipants were all patients with OI from CCRD. After stratified sampling according to the economic level of residential city, 901 patients were proportionally selected and 869 patients completed the survey (response rate: 96.4%).Main outcome measuresDemographic characteristics and KAP information were gathered using a 5-point Likert scale. The score of each dimension of KAP was the sum of the scores of all included items. Χ2 test or Fisher’s exact test was used to compare scores of different items. Ordinal regression was employed to determine the significant factors influencing KAP.ResultsA total of 802 questionnaires were included for analysis. Male respondents accounted for 57.1%, and 29.1% of respondents were of 26~30 years. More than half (50~60%) of patients knew the main symptoms of OI and the treatment of OI-related complications. Almost 80% of patients showed positive attitude. Nearly 60~70% of the patients were relatively able to take appropriate practice regarding OI management. There was a significant correlation between scores of knowledge and attitude, attitude and practice, as well as knowledge and practice. Patients aged 26~30 years, from urban areas and big cities, had higher KAP scores. Male patients showed better performance in knowledge, and highly educated patients perform better in practice.ConclusionsPatients with OI did not have sufficient knowledge on disease care and up-to-date caring guidelines, and their practice regarding health self-management also needs to be improved. Gender, age, educational level and economic level of residence can affect the level of KAP for patients, thus developing targeted and tailored programmes for patients with OI is highly recommended.
Effects of COVID-19 protective measures on the ophthalmological patient examination with an emphasis on gender-specific differences
Authors: Rauchegger Teresa , Osl Antonia , Nowosielski Yvonne , Angermann Reinhard , Palme Christoph , Haas Gertrud , Steger Bernhard 
Published: September 2021

ObjectiveIn response to the COVID-19 pandemic, strict hygiene and containment measures have been instituted in the clinical ophthalmological examination to prevent virus transmission. The aim of this study is to assess the effects of these protective measures on the quality of the examination with an emphasis on gender-specific differences.Methods and analysisAn online survey was sent to ophthalmologists in 10 countries. The collected data included demographics, place of work, current professional status, COVID-19 protective measures and their impact on the quality of the examination. Descriptive statistics were used to analyse the data. Fisher’s exact test was used to analyse gender differences.ResultsA total of 120 responses were collected. 54.0% of the respondents identified as female and 43.4% as male. Over 75% agreed that protective measures made the examination conditions more difficult. The major problems were fogging of the lenses (87.6%) or slit lamp oculars (69.9%), reduced operability of the slit lamp due to protective barriers (60.2%) and time delay due to disinfection measures (68.1%). Significantly more women than men reported that they used filtering face piece (FFP2) instead of surgical masks (p=0.02). More male participants reported that they removed their mask to prevent fogging (p=0.01). 31% of all participants felt that the COVID-19 protective measures reduced the overall quality of slit lamp examination and 43.4% reported a reduced quality of fundoscopic examination.ConclusionCOVID-19 related safety measures reduce the feasibility of the clinical ophthalmological examination. Practicable solutions are required to maintain good examination quality without compromising personal safety.
Effectiveness of an impedance cardiography guided treatment strategy to improve blood pressure control in a real-world setting: results from a pragmatic clinical trial
Authors: Wang Luyan , Lu Yuan , Wang Hongyi , Gu Jianlei , Ma Zheng J , Lian Zheng , Zhang Zhiying , Krumholz Harlan , Sun Ningling 
Published: September 2021

ObjectiveTo test the effectiveness of an impedance cardiography (ICG) guided treatment strategy on improving blood pressure (BP) control in real-world clinical practice.DesignA single-centre, pragmatic randomised trial.SettingA hypertension clinic of the Peking University People’s Hospital in Beijing, China.ParticipantsAdults who sought outpatient care for hypertension in the hypertension clinic at the Peking University People’s Hospital between June and December 2019.InterventionsA computerised clinical decision support of recommending treatment choices to providers based on patients’ haemodynamic profiles measured by ICG.Main outcome measuresChanges in systolic BP (SBP) and diastolic BP (DBP) levels at the follow-up visit 4–12 weeks after baseline. Secondary outcomes included achievement of BP goal of <140/90 mm Hg and the changes in BP by baseline BP, age, sex and body mass index (BMI).ResultsA total of 102 adults (mean age was 54±14 years; 41% were women) completed the study. The mean baseline SBP was 150.9 (SD of 11.5) mm Hg and mean baseline DBP was 91.1 (11.3) mm Hg. At the follow-up visit, the mean SBP and DBP decreased by 19.9 and 11.3 mm Hg in the haemodynamic group, as compared with 12.0 and 4.9 mm Hg in the standard care group (p value for difference between groups <0.001). The proportion of patients achieving BP goal of <140/90 mm Hg in the haemodynamic group was 67%, as compared with 41% in the standard care group (p=0.017). The haemodynamic group had a larger effect on BP reduction consistently across subgroups by age, sex, BMI and baseline BP.ConclusionsAn ICG-guided treatment strategy led to greater reductions in BP levels than were observed with standard care in a real-world population of outpatients with hypertension. There is a need for further validation of this strategy for improving blood pressure treatment selection.Trial registration numberNCT04715698.
Impacts of point cloud density reductions on extracting road geometric features from mobile LiDAR data
Authors: Gargoum Suliman A. , El-Basyouny Karim 
Published: September 2021

The variation in point cloud density is driven by many different factors. This variation is expected to affect the quality of the information extracted from the point clouds, however, the extent to which these variations impact the ability to accurately extract and assess geometric features of highways from point cloud data are unknown. This paper investigates the impacts of point density reduction on the extraction and assessment of four critical geometric features. The density of light detection and ranging (LiDAR) data was first reduced and the different features were extracted at varying levels of point density and on a selection of different highway segments in Alberta, Canada. The information obtained at lower point density was then compared to what was obtained at 100% point density. It was found that clearance assessments and sight distance assessments had low sensitivity to reductions in point density (i.e., reducing the point density to as low as 10% of the original data (30 ppm2 on the pavement surface) yielded results comparable to what was obtained at 100% density (300 ppm2) In contrast, for cross section slope estimation and curve attribute estimation higher sensitivity to point density was observed. These findings are critical for transportation agencies considering the adoption of LiDAR technology to manage elements of their infrastructure and for researchers developing data processing tools and algorithms for the semantic segmentation of transportation features from remotely sensed point clouds.
Designing Bankers’ Pay: Using Contingent Capital to Reduce Risk-Shifting Incentives
Authors: Hilscher Jens , Lazar Sharon Peleg , Raviv Alon 
Published: September 2021

Including contingent convertible bonds (coco) in the capital structure of a bank affects the sensitivity to risk of its equity-based compensation. Such risk-shifting incentives can be reduced if the coco bonds are well-designed. Similarly, we show that compensating executives with well-designed coco bonds can also reduce risk-shifting incentives. In practice, however, most coco bonds have characteristics that result in both stock and coco compensation having large sensitivities to changes in asset risk — equity-based compensation encourages executives to increase risk, coco compensation to reduce risk. We show that a pay package combining both stock and coco can practically eliminate risk-shifting incentives and that it can be implemented with a bank’s preexisting coco bonds.
HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA
Authors: Leung Eric , Han Kathy , Zou Jinfeng , Zhao Zhen , Zheng Yangqiao , Wang Ting Ting , Rostami Ariana , Siu Lillian L. , Pugh Trevor J. , Bratman Scott V. 
Published: September 2021

AbstractPurpose:Human papillomavirus (HPV) DNA offers a convenient circulating tumor DNA (ctDNA) marker for HPV-associated malignancies, but current methods, such as digital PCR (dPCR), provide insufficient accuracy for clinical applications in patients with low disease burden. We asked whether a next-generation sequencing approach, HPV sequencing (HPV-seq), could provide quantitative and qualitative assessment of HPV ctDNA in low disease burden settings.Experimental Design:We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of patients with locally advanced cervix cancer (NCT02388698) and a cohort of patients with oropharynx cancer. HPV-seq results were compared with dPCR. The primary outcome was progression-free survival (PFS) according to end-of-treatment HPV ctDNA detectability.Results:HPV-seq achieved reproducible detection of HPV DNA at levels less than 0.6 copies in cell line data. HPV-seq and dPCR results for patients were highly correlated (R2 = 0.95, P = 1.9 × 10–29) with HPV-seq detecting ctDNA at levels down to 0.03 copies/mL plasma in dPCR-negative posttreatment samples. Detectable HPV ctDNA at end-of-treatment was associated with inferior PFS with 100% sensitivity and 67% specificity for recurrence. Accurate HPV genotyping was successful from 100% of pretreatment samples. HPV ctDNA fragment sizes were consistently shorter than non–cancer-derived cell-free DNA (cfDNA) fragments, and stereotyped cfDNA fragmentomic patterns were observed across HPV genomes.Conclusions:HPV-seq is a quantitative method for ctDNA detection that outperforms dPCR and reveals qualitative information about ctDNA. Our findings in this proof-of-principle study could have implications for treatment monitoring of disease burden in HPV-related cancers. Future prospective studies are needed to confirm that patients with undetectable HPV ctDNA following chemoradiotherapy have exceptionally high cure rates.
Antitumor Activity of the Novel BTK Inhibitor TG-1701 Is Associated with Disruption of Ikaros Signaling in Patients with B-cell Non–Hodgkin Lymphoma
Authors: Ribeiro Marcelo Lima , Reyes-Garau Diana , Vinyoles Meritxell , Profitós Pelejà Núria , Santos Juliana Carvalho , Armengol Marc , Fernández-Serrano Miranda , Sedó Mor Alícia , Bech-Serra Joan J. , Blecua Pedro , Musulen Eva , De La Torre Carolina , Miskin Hari , Esteller Manel , Bosch Francesc , Menéndez Pablo , Normant Emmanuel , Roué Gaël 
Published: September 2021

Abstract

Purpose:
Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non–Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance of phosphoproteomic profiling for the early identification of BTKi responders remains underexplored.

Experimental Design:
A set of six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) with TG-1701, a novel irreversible and highly specific BTKi, were characterized by phosphoproteomic and RNA sequencing (RNA-seq) analysis. The activity of TG-1701 was evaluated in a panel of 11 B-NHL cell lines and mouse xenografts, including two NF-κB- and BTKC481S-driven BTKi-resistant models. Biomarker validation and signal transduction analysis were conducted through real-time PCR, Western blot analysis, immunostaining, and gene knockout (KO) experiments.

Results:
A nonsupervised, phosphoproteomic-based clustering did match the early clinical outcomes of patients with CLL and separated a group of “early-responders” from a group of “late-responders.” This clustering was based on a selected list of 96 phosphosites with Ikaros-pSer442/445 as a potential biomarker for TG-1701 efficacy. TG-1701 treatment was further shown to blunt Ikaros gene signature, including YES1 and MYC, in early-responder patients as well as in BTKi-sensitive B-NHL cell lines and xenografts. In contrast, Ikaros nuclear activity and signaling remained unaffected by the drug in vitro and in vivo in late-responder patients and in BTKC481S, BTKKO, and noncanonical NF-κB models.

Conclusions:
These data validate phosphoproteomic as a valuable tool for the early detection of response to BTK inhibition in the clinic, and for the determination of drug mechanism of action.