bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizure prophylaxis following aneurysmal subarachnoid haemorrhage (SPSAH): study protocol for a multicentre randomised placebo-controlled trial of short-term sodium valproate prophylaxis in patients with acute subarachnoid haemorrhage
Authors: Chen Yuqi , Fang Mei , Wu Pei , Xie Zhiyi , Wu Honggang , Wu Qiaowei , Xu Shancai , Li Yuchen , Sun Bowen , Pang Bo , Zheng Niandong , Zhang Jianmin , Hu Xin , You Chao 
Published: May 2022

IntroductionSeizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping.Methods and analysisIn this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0–2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat.Ethics and disseminationThis study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR.Trial registration numberChiCTR.org identifier: ChiCTR2100050161.
Physical activity and sedentary behaviour interventions for people living with both frailty and multiple long-term conditions: a scoping review protocol
Authors: Young Hannah M L , Yates Thomas , Dempsey Paddy C , Herring Louisa Y , Henson Joseph , Sargeant Jack , Curtis Ffion , Sathanapally Harini , Highton Patrick J , Hadjiconstantinou Michelle , Pritchard Rebecca , Lock Selina , Singh Sally J , Davies Melanie J 
Published: May 2022

IntroductionThe number of people living with multiple long-term conditions (MLTCs) is predicted to rise. Within this population, those also living with frailty are particularly vulnerable to poor outcomes, including decreased function. Increased physical activity, including exercise, has the potential to improve function in those living with both MLTCs and frailty but, to date, the focus has remained on older people and may not reflect outcomes for the growing number of younger people living with MLTCs and frailty. For those with higher burdens of frailty and MLTCs, physical activity may be challenging. Tailoring physical activity in response to symptoms and periods of ill-health, involving family and reducing sedentary behaviour may be important in this population. How the tailoring of interventions has been approached within existing studies is currently unclear. This scoping review aims to map the available evidence regarding these interventions in people living with both frailty and MLTCs.Methods and analysisWe will use a six-stage process: (1) identifying the research questions; (2) identifying relevant studies (via database searches); (3) selecting studies; (4) charting the data; (5) collating and summarising and (6) stakeholder consultation. Studies will be critically appraised using the Mixed Methods Appraisal Tool.Ethics and disseminationAll data in this project will be gathered through database searches. Stakeholder consultation will be undertaken with an established patient and public involvement group. We will disseminate our findings via social media, publication and engagement meetings.
Development of a concussion public policy on prevention, management and education for schools using expert consensus
Authors: Mylabathula Swapna , Macarthur Colin , Guttmann Astrid , Colantonio Angela , Tator Charles 
Published: May 2022

ObjectivesConcussions are a major public health concern, and, thus, specific policies have been developed for implementation targeting vulnerable populations such as school-aged children and youth in the school setting, in whom the majority of concussions are sports related. Currently, concussion policies exist in various jurisdictions, including Canada’s first concussion policy for schools, Ontario’s PPM158, initiated in 2014. However, these policies are often variable in terms of content and comprehensiveness. Our objective was to develop a consensus for the content of concussion policy for schools.MethodsFollowing a pilot study in one Ontario school board in 2015, which identified missing elements in existing concussion policy, we employed a modified Delphi method to develop consensus for the content of concussion public policy for schools. We used an integrated knowledge translation approach with participation from a multidisciplinary stakeholder group of 20 experts including principals, school board directors, physicians, policymakers, public health representatives and parents.ResultsBased on the experts, we created a list of 30 policy recommendations for concussion policy in the school setting. This comprehensive list reflects the diverse perspectives of the experts and addresses the role of parents, teachers, coaches, school administrators, referees, trainers, physicians/nurse practitioners, public health and students.ConclusionsThis is the first expert consensus for content of concussion public policy for schools and can be used for policy development or enhancement in schools in other jurisdictions. We provide a comprehensive list of 30 recommendations to guide best practices for policy development and implementation to enhance school-based concussion prevention and management.
Achieving gains in state and local child safety systems and workforce development: application of the framework for quality improvement and innovation in child safety
Authors: Leonardo Jennifer B , Ali Bina , Stern-Carusone Jenny , Katradis Maria 
Published: May 2022

ObjectiveThis study investigated the application of the Children’s Safety Network (CSN) Framework for Quality Improvement and Innovation in Child Safety through the Child Safety Learning Collaborative (CSLC).MethodsThe CSN Framework was used by 26 state/jurisdiction teams that participated in cohort 1 of the CSLC, from November 2018 to April 2020. The aim was to strengthen child safety systems and the workforce to spread child safety evidence-based and evidence-informed strategies and programmes for children and adolescents ages <1–19 years.ProceduresParticipating teams’ child safety system development, workforce development, engagement in the CSLC, challenges encountered and overall satisfaction with the CSLC were assessed through ongoing CSLC participation records and an end-of-cohort survey (survey response rate: 73.1%).ResultsTeams showed an average change of 2.4-fold increase in the spread of evidence-based and evidence-informed child safety strategies and programmes, indicating improvement in child safety systems. Knowledge development on CSLC tools and strategies was reported by 77.8% of teams, with 55.5% reporting CSLC tools and strategies contributed to workforce development. Over two-thirds (70.6%) reported being satisfied or very satisfied with the CSLC, but identified some challenges, including staff turnover and the need to strengthen partnerships. All teams demonstrated engagement in the CSLC, based on participation in a virtual meeting, learning session or a monthly report submission.ConclusionsDespite challenges, teams continued to participate in the CSLC, recognising the importance of collaborative learning. The CSN Framework is helpful for state/jurisdiction teams to improve child safety systems and develop their workforce.
Implementation of the updated NICE haematological cancers (NG47) improving outcomes guidelines across Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) in England: a UK NEQAS LI survey
Authors: Cartwright Ashley , Snowden John A , Whitehouse Helen , Scott Stuart , Whitby Liam 
Published: May 2022

AimsHaematological malignancies represent a diverse group of diseases with complex diagnostic requirements. National Institute for Health and Care Excellence (NICE) Haematological Cancer: Improving Outcomes Guidance was published in 2003 and updated in 2016 (NG47), providing recommendations for service delivery including Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDSs). This survey assessed the implementation of NG47 guidelines, with a specific focus on implementation in relation to laboratory SIHMDS delivery.MethodsA survey was issued to the 17 SIHMDSs identified in England. The questionnaire covered laboratory configuration, information systems, integrated reporting and multidisciplinary team (MDT) working recommendations.ResultsIn the 10 responding SIHMDS, full implementation of recommendations was not achieved. Higher levels of implementation were reported in ‘colocated’ services compared with ‘networked’ SIHMDS. Increased guideline implementation was reported with longer duration since initial establishment of a SIHMDS and for laboratory based as opposed to clinical (MDT) reporting recommendations.ConclusionsOur survey highlights variable implementation of NICE guidance across SIHMDS, with likely inequity of access, standardisation and quality in haemato-oncology diagnostics. Provision of a more structured framework for guideline implementation could assist in increasing compliance to meet the goals of quality and equity of access to harmonised haemato-oncology diagnostics across the NHS in England. This would provide a basis for evaluating the clinical benefits and health economic impact of the SIHMDS model on patient care and outcomes.
Departure to pure de Sitter geometry based on Planck data
Authors: Suratgar K. , Mohsenzadeh M. , Yusofi E. , Tagizadeh-Farahmand F. 
Published: May 2022

In this paper, we will obtain the basic parameters of primordial inflation such as power spectrum, scalar spectral index, and tensor-to-scalar ratio as a function of Hankel index [Formula: see text] for asymptotic-de Sitter inflation and then, based on the observational constraints on these parameters from Planck data, we obtain the allowable range for index [Formula: see text]. We will show that only the non-phantom phase is acceptable for quasi-de Sitter inflation at early universe. As a significant result, both of the primordial and late accelerating expansion are always in a quasi-vacuum phase (with [Formula: see text]) and it has never been in a pure-vacuum phase (with [Formula: see text]), i.e. cosmological constant. Therefore, based on our recent finding [E. Yusofi, M. Khanpour, B. Khanpour, M. A. Ramzanpour and M. Mohsenzadeh, Surface tension of cosmic voids as a possible source for dark energy, Mon. Not. R. Astron. Soc. 511 (2022) L82], we offer the surface tension of cosmic voids as a suitable alternative to the cosmological constant [Formula: see text], for accelerating universe.
Real-Time Hair Filtering with Convolutional Neural Networks
Authors: Currius Roc R. , Assarsson Ulf , Sintorn Erik 
Published: May 2022

Rendering of realistic-looking hair is in general still too costly to do in real-time applications, from simulating the physics to rendering the fine details required for it to look natural, including self-shadowing.
We show how an autoencoder network, that can be evaluated in real time, can be trained to filter an image of few stochastic samples, including self-shadowing, to produce a much more detailed image that takes into account real hair thickness and transparency.
Online Application Guidance for Heterogeneous Memory Systems
Authors: Olson M. Ben , Kammerdiener Brandon , Jantz Michael R. , Doshi Kshitij A. , Jones Terry 
Published: May 2022

As scaling of conventional memory devices has stalled, many high-end computing systems have begun to incorporate alternative memory technologies to meet performance goals. Since these technologies present distinct advantages and tradeoffs compared to conventional DDR* SDRAM, such as higher bandwidth with lower capacity or vice versa, they are typically packaged alongside conventional SDRAM in a heterogeneous memory architecture. To utilize the different types of memory efficiently, new data management strategies are needed to match application usage to the best available memory technology. However, current proposals for managing heterogeneous memories are limited, because they either (1) do not consider high-level application behavior when assigning data to different types of memory or (2) require separate program execution (with a representative input) to collect information about how the application uses memory resources.
This work presents a new data management toolset to address the limitations of existing approaches for managing complex memories. It extends the application runtime layer with automated monitoring and management routines that assign application data to the best tier of memory based on previous usage, without any need for source code modification or a separate profiling run. It evaluates this approach on a state-of-the-art server platform with both conventional DDR4 SDRAM and non-volatile Intel Optane DC memory, using both memory-intensive high-performance computing (HPC) applications as well as standard benchmarks. Overall, the results show that this approach improves program performance significantly compared to a standard unguided approach across a variety of workloads and system configurations. The HPC applications exhibit the largest benefits, with speedups ranging from 1.4× to 7× in the best cases. Additionally, we show that this approach achieves similar performance as a comparable offline profiling-based approach after a short startup period, without requiring separate program execution or offline analysis steps.
Impact of Exercise on Susceptibility and Severity of COVID-19 in Patients with Cancer: A Retrospective Study
Authors: Bliss Joshua W. , Lavery Jessica A. , Underwood Whitney P. , Chun Su S. , Fickera Gina A. , Lee Catherine P. , Corcoran Stacie , Maloy Molly A. , Polubriaginof Fernanda C. , Kelly Daniel W. , Scott Jessica M. , Boutros Paul C. , Moskowitz Chaya S. , Jones Lee W. 
Published: May 2022

Abstract

Background:
Modifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known.

Methods:
We identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical–epidemiologic covariates.

Results:
Twenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44–0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P &gt; 0.9).

Conclusions:
Exercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity.

Impact:
This study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required.
Genetic Susceptibility in Understanding of Pancreatic Ductal Adenocarcinoma Risk: A Decade-Long Effort of the PANDORA Consortium
Authors: Vodickova Ludmila , Horak Josef , Vodicka Pavel 
Published: May 2022

Abstract
Pancreatic cancer, a complex disease, emerges as a severe health problem worldwide and it exhibits a poor prognosis and high mortality. Risk factors associated with sporadic pancreatic cancer remain poorly understood, even less is known about disease prognosis due to its rapid progression. The PANcreatic Disease ReseArch (PANDoRA) consortium, of which the authors are members, was established to coordinate the efforts of different research groups to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. PANDoRA consortium has contributed to the identification of several low-penetrance risk loci for the disease both by candidate variants approach and genome-wide association studies, including those in cell-cycle and DNA damage response, telomere homeostasis, SCL and ABC transporters, ABO locus variability, mitochondrial metabolism and it participated on collaborative genome-wide association study approach and implementation of a search for functional-based pancreatic cancer risk loci and long noncoding RNAs. Complex studies covering genetic, environmental and microenvironmental factors in the pancreatic cancer onset, progression and its prognosis are warranted.
Inhibition of Oxidized Nucleotide Sanitation By TH1579 and Conventional Chemotherapy Cooperatively Enhance Oxidative DNA Damage and Survival in AML
Authors: Centio Anders , Estruch Montserrat , Reckzeh Kristian , Sanjiv Kumar , Vittori Camilla , Engelhard Sophia , Warpman Berglund Ulrika , Helleday Thomas , Theilgaard-Mönch Kim 
Published: May 2022

Abstract
Currently, the majority of patients with acute myeloid leukemia (AML) still die of their disease due to primary resistance or relapse toward conventional reactive oxygen species (ROS)- and DNA damage–inducing chemotherapy regimens. Herein, we explored the therapeutic potential to enhance chemotherapy response in AML, by targeting the ROS scavenger enzyme MutT homolog 1 (MTH1, NUDT1), which protects cellular integrity through prevention of fatal chemotherapy-induced oxidative DNA damage. We demonstrate that MTH1 is a potential druggable target expressed by the majority of patients with AML and the inv(16)/KITD816Y AML mouse model mimicking the genetics of patients with AML exhibiting poor response to standard chemotherapy (i.e., anthracycline & cytarabine). Strikingly, combinatorial treatment of inv(16)/KITD816Y AML cells with the MTH1 inhibitor TH1579 and ROS- and DNA damage-inducing standard chemotherapy induced growth arrest and incorporated oxidized nucleotides into DNA leading to significantly increased DNA damage. Consistently, TH1579 and chemotherapy synergistically inhibited growth of clonogenic inv(16)/KITD816Y AML cells without substantially inhibiting normal clonogenic bone marrow cells. In addition, combinatorial treatment of inv(16)/KITD816Y AML mice with TH1579 and chemotherapy significantly reduced AML burden and prolonged survival compared with untreated or single treated mice. In conclusion, our study provides a rationale for future clinical studies combining standard AML chemotherapy with TH1579 to boost standard chemotherapy response in patients with AML. Moreover, other cancer entities treated with ROS- and DNA damage–inducing chemo- or radiotherapies might benefit therapeutically from complementary treatment with TH1579.
Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts
Authors: Vidimar Vania , Park Minyoung , Stubbs Caleb K. , Ingram Nana K. , Qiang Wenan , Zhang Shanshan , Gursel Demirkan , Melnyk Roman A. , Satchell Karla J.F. 
Published: May 2022

Abstract
The lack of effective RAS inhibition represents a major unmet medical need in the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, we investigate the anticancer activity of RRSP-DTB, an engineered biologic that cleaves the Switch I of all RAS isoforms, in KRAS-mutant PDAC cell lines and patient-derived xenografts (PDX). We first demonstrate that RRSP-DTB effectively engages RAS and impacts downstream ERK signaling in multiple KRAS-mutant PDAC cell lines inhibiting cell proliferation at picomolar concentrations. We next tested RRSP-DTB in immunodeficient mice bearing KRAS-mutant PDAC PDXs. Treatment with RRSP-DTB led to ≥95% tumor regression after 29 days. Residual tumors exhibited disrupted tissue architecture, increased fibrosis and fewer proliferating cells compared with controls. Intratumoral levels of phospho-ERK were also significantly lower, indicating in vivo target engagement. Importantly, tumors that started to regrow without RRSP-DTB shrank when treatment resumed, demonstrating resistance to RRSP-DTB had not developed. Tracking persistence of the toxin activity following intraperitoneal injection showed that RRSP-DTB is active in sera from immunocompetent mice for at least 1 hour, but absent after 16 hours, justifying use of daily dosing. Overall, we report that RRSP-DTB strongly regresses hard-to-treat KRAS-mutant PDX models of pancreatic cancer, warranting further development of this pan-RAS biologic for the management of RAS-addicted tumors.
Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumors
Authors: Ishi Yukitomo , Zhang Yongzhan , Zhang Ali , Sasaki Takahiro , Piunti Andrea , Suri Amreena , Watanabe Jun , Abe Kouki , He Xingyao , Katagi Hiroaki , Bhalla Pankaj , Natsumeda Manabu , Zou Lihua , Shilatifard Ali , Hashizume Rintaro 
Published: May 2022

Abstract
Aberrant activity of the H3K27 modifiers EZH2 and BRD4 is an important oncogenic driver for atypical teratoid/rhabdoid tumor (AT/RT), and each is potentially a possible therapeutic target for treating AT/RT. We, therefore, determined whether targeting distinct histone modifier activities was an effective approach for treating AT/RT. The effects of EZH2 and BRD4 inhibition on histone modification, cell proliferation, and cell invasion were analyzed by immunoblotting, MTS assay, colony formation assay, and cell invasion assay. RNA- and chromatin immunoprecipitation-sequencing were used to determine transcriptional and epigenetic changes in AT/RT cells treated with EZH2 and BRD4 inhibitors. We treated mice bearing human AT/RT xenografts with EZH2 and BRD4 inhibitors. Intracranial tumor growth was monitored by bioluminescence imaging, and the therapeutic response was evaluated by animal survival. AT/RT cells showed elevated levels of H3K27 trimethylation (H3K27me3) and H3K27 acetylation (H3K27ac), with expression of EZH2 and BRD4, and lack of SMARCB1 proteins. Targeted inhibition of EZH2 and BRD4 activities reduced cell proliferation and invasiveness of AT/RT in association with decreasing H3K27me3 and H3K27ac. Differential genomic occupancy of H3K27me3 and H3K27ac regulated specific gene expression in response to EZH2 and BRD4 inhibitions. A combination of EZH2 and BRD4 inhibition increased the therapeutic benefit in vitro and in vivo, outperforming either monotherapy. Overall, histones H3K27me3 and H3K27ac were elevated in AT/RT cells and distributed in distinct chromatin regions to regulate specific gene expression and to promote AT/RT growth. Targeting EZH2 and BRD4 activity is, therefore, a potential combination therapy for AT/RT.