bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Deutetrabenazine Treatment Is Associated With Continued Improvement in Tardive Dyskinesia in the Completed 3-Year Open-Label Extension Study
Authors: Hauser Robert A. , Barkay Hadas , Fernandez Hubert H. , Factor Stewart A. , Jimenez-Shahed Joohi , Gross Nicholas , Marinelli Leslie , Wilhelm Amanda , Gordon Mark Forrest , Savola Juha-Matti , Anderson Karen E. 
Published: May 2021

AbstractBackgroundThe 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C−20) evaluated long-term efficacy and safety of deutetrabenazine in TD.MethodsPatients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being “much improved” or “very much improved” on Clinical Global Impression of Change (CGIC).Results343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE]: 38.7±0.66mg/day), mean change from baseline in AIMS score was –4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose: 39.3±0.75mg/day), mean change from baseline in AIMS score was –5.4±0.33; 65% of patients experienced treatment success. At Week 145 (n=160; dose: 39.4±0.83mg/day), mean change from baseline in AIMS score was –6.6±0.37; 73% of patients experienced treatment success. Treatment was generally well tolerated across 723 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) for akathisia/restlessness were 0.01, somnolence/sedation were 0.07, and symptoms which may represent parkinsonism or depression were 0.08 each.ConclusionsPatients who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS scores. Findings from this open-label trial with response-driven dosing suggest the possibility of increasing benefit over time.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study
Authors: Frank Samuel , Testa Claudia M. , Stamler David , Kayson Elise , Oakes David , Vaughan Christina , Goldstein Jody , Whaley Jacquelyn , Davis Mat D. , Gordon Mark Forrest , Savola Juha-Matti ,   on behalf of the Huntington Study Group ARC-HD Investigators
Published: May 2021

AbstractBackgroundChorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.MethodsPatients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.ResultsOf 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.ConclusionsThe type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Overcoming the Challenges of the Mental Health Care System in United States in the Aftermath of COVID-19
Authors: Radfar Amir , Caceres Maria Mercedes Ferreira , Sosa Juan Pablo , Filip Irina 
Published: May 2021

AbstractStudy Objective(s)The impact of pandemic events such as the coronavirus (COVID-19) pandemic led to an economic crisis worldwide as well as an increase of mental health problems. In the United States, the gaps in the mental health care system struggle to meet the needs of vulnerable populations and have caused a major public health problem. We aim to increase the awareness of health care professionals, psychiatrists, and policy makers regarding failures and gaps in the mental health care system and suggest new ideas to overcome the growing burden of mental disorders.MethodWe utilized data from PubMed, Science Direct, Cochrane, Embase and Clinicaltrials.gov databases to analyze available information on the US mental health system. We included any relevant articles addressing the prevalence of mental diseases, disparities and the gaps for an accessible and affordable mental health system, as well as the psychological impact of COVID-19 pandemic.Keywords‘COVID-19’, ‘Coronavirus’, ‘SARS-CoV-2’, ‘mental health’, ‘Health, Mental’ were used.ResultsFollowing scoping review of several studies we noticed that while prevalence of mental health problems in the US varies between states and socio-demographic groups, it is among the top 10 causes of premature death and disability in adults. We noticed that mental health problems are currently one of the costliest public health issues in the healthcare system. Tracking Poll from one of the studies in our scoping review suggested that financial inequities are magnified by the COVID-19 pandemic and that psychological distress was substantially larger among respondents with lower income (33%), Hispanics (28%) and Blacks (26%). Furthermore, in another poll 62% of US population are shown to be anxious due to COVID-19. We observed that the prevalence of reported symptoms of psychological distress among US adults increased when compared to 2018. Common barriers such as failure of accessibility, insufficient funding, insufficient psychiatric beds, limited insurance access and economic burden, clinician shortages, fragmented care, insufficient mental health care policies and insufficient education and awareness about mental illness become more prominent during the COVID-19 pandemic era.ConclusionsThe impact of COVID-19 on mental health is alarming, which affects public health and has made the health care system more vulnerable. Pandemic events not only cause acute negative impact, they also result in long-lasting health problems, isolation and stigma. The COVID-19 pandemic threatens the mental health of the population and its long-term consequences can lead to a secondary pandemic. The outcomes of the COVID-19 pandemic on mental health emphasize the need for policies and strategies to support and strengthen a concerted effort to address its burden on the US mental health care system. In addition, it magnifies the need for high quality and well-funded research for future pandemics.
A Multiparametric MRI Protocol for Evaluation of Cognitive Insufficiency, Dementia and Traumatic Brain Injury (TBI): A Case Series
Authors: Sherman John L. , Kutz Christen F. , Szymczak Mitchell S. , York Deborah , Adams Laurence J. 
Published: May 2021

AbstractBackgroundThe purpose of this work was to determine the extent to which a multiparametric magnetic resonance imaging (MRI) approach to patients with dementia and/or traumatic brain injury (TBI) can help to determine the most likely diagnosis and the prognosis of these patients.ObjectiveVolumetric brain MRI alone is recognized as a useful imaging tool to differentiate behavioral variant frontotemporal dementia (bvFTD) from the more common Alzheimer’s disease (AD). Our objective is to create a protocol that will provide additional non-standard, objective imaging data that can be utilized clinically to distinguish common and uncommon forms of dementia and TBI. As patients with these diseases are increasingly presenting to clinical practice, our ability to combine multiple parameters within the standard 30-minute or 45-minute (pre- and post-contrast) MRI exams has high potential to affect current and future clinical practice.MethodsAll MRI studies were performed on 1.5 T MRI GE 450w or GE HDx imagers. All patients were seen clinically in outpatient practices. All techniques are FDA approved. The 30 minute protocol utilized T2w FSE 3 mm, 2.5 mm SWAN, 3D T1 sagittal 1.2 mm, DWI 5 mm, 3D FLAIR 1.2 mm, 2.5 mm SWAN (susceptibility sensitive), 3D T1 sagittal 1.2 mm, arterial spin labeling perfusion, posterior cingulate single voxel PRESS MR spectroscopy and NeuroQuant automated volumetric analysis and LesionQuant automated lesion detection and measurement. The 45-minute TBI protocol added diffusion tensor imaging, MR spectroscopy (MRS) of normal appearing frontal white matter and 3D gadolinium enhanced technique.ResultsThe combination of multiparametric data together with standard imaging and clinical information allowed radiologic interpretation that was able to focus on 1–2 specific diagnoses and to indicate those patients in which a combination of pathologies was most likely. Neurologists, gerontologists, neuropsychologists and psychiatric specialists used these data and our summary conclusions to develop more specific diagnoses, treatments and prognoses.ConclusionsReadily available MRI techniques can be added to standard imaging to markedly improve the usefulness of the radiologic opinion in cases of subjective cognitive insufficiency, clinical mild cognitive insufficiency, behavioral pathologies, dementia and post-traumatic brain syndromes.
The Effectiveness of a Neighbor-to-Neighbor Get-Out-the-Vote Program: Evidence from the 2017 Virginia State Elections
Authors: Handan-Nader Cassandra , Ho Daniel E. , Morantz Alison , Rutter Tom A. 
Published: May 2021

Abstract
We analyze the results of a neighbor-to-neighbor, grassroots get-out-the-vote (GOTV) drive in Virginia, in which unpaid volunteers were encouraged to contact at least three nearby registered voters who were likely co-partisans yet relatively unlikely to vote in the 2017 state election. To measure the campaign’s effectiveness, we used a pairwise randomization design whereby each volunteer was assigned to one randomly selected member of the most geographically proximate pair of voters. Because some volunteers unexpectedly signed up to participate outside their home districts, we analyze the volunteers who adhered to the original hyper-local program design separately from those who did not. We find that the volunteers in the original program design drove a statistically significant 2.3% increase in turnout, which was concentrated in the first voter pair assigned to each volunteer. We discuss implications for the study and design of future GOTV efforts.
Biogeochemical Responses to Nutrient Fluxes in the Open South China Sea: A 3‐D Modeling Study
Authors: Shuai Yiping , Li Qian P. , Wu Zhengchao 
Published: May 2021

AbstractRecent Bio‐Argo observations revealed a spatial difference of seasonal chlorophyll‐a pattern in the South China Sea (SCS) with permanent subsurface chlorophyll‐a maximum layer in the central SCS (CSCS) but intense winter chlorophyll‐a bloom in the northern SCS (NSCS). A three‐dimensional physical‐biogeochemical model was used to simulate the temporal change of upper ocean physics and biogeochemistry of the open SCS following the trajectories of the two Bio‐Argo floats to explore mechanisms driving the difference between the two very contrasting marine ecosystems. The model reasonably reproduced the Bio‐Argo vertical observations in both regions. In the model, high nitrate fluxes had supported a strong winter chlorophyll‐a and productivity in the NSCS, while low nitrate fluxes in the CSCS leading to a stable subsurface chlorophyll‐a layer throughout the year. We found that nitrate fluxes in the north were controlled by diffusion during the early winter but by advection during the late winter. Both buoyancy and wind forcing contributed to increased diffusive nutrient fluxes by mixing nutrients below the nutricline in the early winter of the NSCS. A strong upwelling during the late winter in the north was supported by eddy‐Ekman pumping, particularly the nonlinear effect induced by eddy vorticity gradient. The finding is consistent with the change of vertical advection in both directions and magnitudes in the north throughout the year. The eddy‐driven difference in advection between the two regions was further confirmed by substantially larger eddy kinetic energies and eddy activities in the north.
Toward Entrainment Thresholds in Fluvial Plucking
Authors: Hurst A. A. , Anderson R. S. , Crimaldi J. P. 
Published: May 2021

AbstractPlucking of blocks is an important, but understudied component of erosion in steep bedrock rivers. With the goal of developing realistic entrainment thresholds for use in bedrock channel evolution models, we re‐formulate the block entrainment problem. We derive the force and torque balances representing sliding and toppling of blocks occupying backward‐facing steps in the channel floor. We employ a computational fluid dynamics package to calculate the pressures and shear stresses on all faces of such a block, therefore explicitly representing the horizontally directed drag force and vertically directed lift force. We find that the pressure difference between the upstream and downstream block faces can significantly impact the force and torque balances. At typical flows, downstream pressure becomes ∼1%–2% lower than total upstream pressure, reflecting the reduction in fluid pressures in the recirculation zone. This pressure difference scales with the block Reynolds number squared and dramatically increases if the block protrudes above the plane of the upstream ledge. The resulting net downstream‐directed force both adds to the forces promoting sliding and provides a torque about the lower downstream corner of the block. Armed with the full set of forces on a block, we explore the roles of block geometry, flow velocity and depth, toppling pivot point location, and bed slope in facilitating sliding and toppling. Incorporating the small pressure difference between upstream and downstream faces greatly lowers the threshold for plucking, and suggests that blocks on river channel floors should move at lower and hence more frequent discharges than previously thought.
The effect of physical activity intervention and nutritional habits on anthropometric measures in elementary school children: the health oriented pedagogical project (HOPP)
Authors: Goswami Nandu , Trozic Irhad , Fredriksen Maren Valand , Fredriksen Per Morten 
Published: May 2021

Abstract
Background
Overweight and obesity are a burden of the modern world that requires urgent action. Prevention has proven to be efficient in the fight against overweight and obesity. As many children gain excessive weight at an early age, intervention during school years are important. While daily physical activity (PA) is known to have an influence on overweight and obesity prevention, the importance of a healthy lifestyle, including dietary habits, should not be underestimated. The aim of this study was to assess how a combination of daily PA and healthy/unhealthy diet affect the anthropometric measures of 4th graders in Norway.

Methods
The Health Oriented Pedagogical Project (HOPP) is a longitudinal intervention in primary school children, which includes increased amount of daily physical activity during teaching– active learning. Assessed were weight, muscle and bone mass, as well as fat mass, using a bio-impedance Tanita scale. A dietary survey, Ungkost 2000, with 18 multiple-choice questions was used to evaluate the overall nutrition characteristics of the children.

Results
Between 2015 and 2018, a total of 917 (intervention group n = 614, control group n = 303) 4th graders from nine different schools from the south–east part of Norway participated. We observed that daily PA and a regular healthy diet increases—while an unhealthy diet decreases—muscle and bone mass despite daily PA. Daily PA appears to counteract some of the effects of an unhealthy diet on weight and fat mass. In addition, daily PA and a regular intake of fruits and berries lowers weight and fat mass in children with overweight.

Conclusion
Combination of daily 45-minute of PA and a healthy diet leads to reductions in body weight and incease in muscle and bone mass in elementary school children.
Gene expression derived from alternative promoters improves prognostic stratification in multiple myeloma
Authors: Valcárcel Luis V. , Amundarain Ane , Kulis Marta , Charalampopoulou Stella , Melnick Ari , San Miguel Jesús , Martín-Subero José I. , Planes Francisco J. , Agirre Xabier , Prosper Felipe 
Published: May 2021

AbstractClinical and genetic risk factors are currently used in multiple myeloma (MM) to stratify patients and to design specific therapies. However, these systems do not capture the heterogeneity of the disease supporting the development of new prognostic factors. In this study, we identified active promoters and alternative active promoters in 6 different B cell subpopulations, including bone-marrow plasma cells, and 32 MM patient samples, using RNA-seq data. We find that expression initiated at both regular and alternative promoters was specific of each B cell subpopulation or MM plasma cells, showing a remarkable level of consistency with chromatin-based promoter definition. Interestingly, using 595 MM patient samples from the CoMMpass dataset, we observed that the expression derived from some alternative promoters was associated with lower progression-free and overall survival in MM patients independently of genetic alterations. Altogether, our results define cancer-specific alternative active promoters as new transcriptomic features that can provide a new avenue for prognostic stratification possibilities in patients with MM.
Viral dynamics and antibody responses in people with asymptomatic SARS-CoV-2 infection
Authors: Sui Zhiwei , Dai Xinhua , Lu Qingbin , Zhang Yulan , Huang Min , Li Shufen , Peng Tao , Xie Jie , Zhang Yongzhuo , Wu Chunchen , Xia Jianbo , Dong Lianhua , Yang Jiayi , Huang Wenfeng , Liu Siyuan , Wang Ziquan , Li Ke , Yang Qingfang , Zhou Xi , Wu Ying , Liu Wei , Fang Xiang , Peng Ke 
Published: May 2021

AbstractOver 40% of the coronavirus disease 2019 (COVID-19) COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 pandemic. Here, we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May 2020. Asymptomatic individuals were admitted to the government-designated centralized sites in accordance with policy. The incidence rate of asymptomatic infection is ~2.92/100,000. These individuals had low viral copy numbers (peaked at 315 copies/mL) and short-lived antibody responses with the estimated diminish time of 69 days. The antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 days. These results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection, which has recently been reported in recovered COVID-19 patients. This casts doubt on the efficacy of forming “herd-immunity” through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.
Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer
Authors: Ring Alistair , Battisti Nicolò Matteo Luca , Reed Malcolm W. R. , Herbert Esther , Morgan Jenna L. , Bradburn Michael , Walters Stephen J. , Collins Karen A. , Ward Sue E. , Holmes Geoffrey R. , Burton Maria , Lifford Kate , Edwards Adrian , Robinson Thompson G. , Martin Charlene , Chater Tim , Pemberton Kirsty J. , Brennan Alan , Cheung Kwok Leung , Todd Annaliza , Audisio Riccardo A. , Wright Juliet , Simcock Richard , Green Tracey , Revell Deirdre , Gath Jacqui , Horgan Kieran , Holcombe Chris , Winter Matthew C. , Naik Jay , Parmeshwar Rishi , Gosney Margot A. , Hatton Matthew Q. , Thompson Alastair M. , Wyld Lynda ,   on behalf of the Age Gap TMG, Collins Karen , Ward Sue , Holmes Geoff , Morgan Jenna , Bradburn Mike , Walters Stephen , Burton Maria , Lifford Kate , Edwards Adrian , Brain Kate , Ring Alistair , Robinson Thomson , Pemberton Kirsty , Shrestha Anne , Nettleship Anthony , Richards Paul , Cheung Kwok Leung , Harder Helena , Audisio Riccardo , Battisti Nicolò Matteo Luca , Wright Juliette , Simcock Richard , Murray Chris , Thomson Alistair M. , Gosney Margot , Hatton Matthew , Armitage Fiona , Patnick Julietta , Green Tracy , Revill Deirdre , Gath Jacqui , Horgan Kieran , Holcombe Chris , Winter Matt 
Published: May 2021

Abstract
Background
Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy.

Methods
A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage.

Results
Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed.

Conclusions
Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient.

Trial Registration
ISRCTN 46099296