bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMPQ-1 binds selectively to (3+1) hybrid topologies in human telomeric G-quadruplex multimers
Authors: Gao Chao , Liu Zhu , Hou Haitao , Ding Jieqin , Chen Xin , Xie Congbao , Song Zibing , Hu Zhe , Feng Mingqian , Mohamed Hany I , Xu Shengzhen , Parkinson Gary N , Haider Shozeb , Wei Dengguo 
Published: October 2020

AbstractA single G-quadruplex forming sequence from the human telomere can adopt six distinct topologies that are inter-convertible under physiological conditions. This presents challenges to design ligands that show selectivity and specificity towards a particular conformation. Additional complexity is introduced in differentiating multimeric G-quadruplexes over monomeric species, which would be able to form in the single-stranded 3′ ends of telomeres. A few ligands have been reported that bind to dimeric quadruplexes, but their preclinical pharmacological evaluation is limited. Using multidisciplinary approaches, we identified a novel quinoline core ligand, BMPQ-1, which bound to human telomeric G-quadruplex multimers over monomeric G-quadruplexes with high selectivity, and induced the formation of G-quadruplex DNA along with the related DNA damage response at the telomere. BMPQ-1 reduced tumor cell proliferation with an IC50 of ∼1.0 μM and decreased tumor growth rate in mouse by half. Biophysical analysis using smFRET identified a mixture of multiple conformations coexisting for dimeric G-quadruplexes in solution. Here, we showed that the titration of BMPQ-1 shifted the conformational ensemble of multimeric G-quadruplexes towards (3+1) hybrid-2 topology, which became more pronounced as further G-quadruplex units are added.
Project Score database: a resource for investigating cancer cell dependencies and prioritizing therapeutic targets
Authors: Dwane Lisa , Behan Fiona M , Gonçalves Emanuel , Lightfoot Howard , Yang Wanjuan , van der Meer Dieudonne , Shepherd Rebecca , Pignatelli Miguel , Iorio Francesco , Garnett Mathew J 
Published: October 2020

AbstractCRISPR genetic screens in cancer cell models are a powerful tool to elucidate oncogenic mechanisms and to identify promising therapeutic targets. The Project Score database (https://score.depmap.sanger.ac.uk/) uses genome-wide CRISPR–Cas9 dropout screening data in hundreds of highly annotated cancer cell models to identify genes required for cell fitness and prioritize novel oncology targets. The Project Score database currently allows users to investigate the fitness effect of 18 009 genes tested across 323 cancer cell models. Through interactive interfaces, users can investigate data by selecting a specific gene, cancer cell model or tissue type, as well as browsing all gene fitness scores. Additionally, users can identify and rank candidate drug targets based on an established oncology target prioritization pipeline, incorporating genetic biomarkers and clinical datasets for each target, and including suitability for drug development based on pharmaceutical tractability. Data are freely available and downloadable. To enhance analyses, links to other key resources including Open Targets, COSMIC, the Cell Model Passports, UniProt and the Genomics of Drug Sensitivity in Cancer are provided. The Project Score database is a valuable new tool for investigating genetic dependencies in cancer cells and the identification of candidate oncology targets.
DBAASP v3: database of antimicrobial/cytotoxic activity and structure of peptides as a resource for development of new therapeutics
Authors: Pirtskhalava Malak , Amstrong Anthony A , Grigolava Maia , Chubinidze Mindia , Alimbarashvili Evgenia , Vishnepolsky Boris , Gabrielian Andrei , Rosenthal Alex , Hurt Darrell E , Tartakovsky Michael 
Published: October 2020

AbstractThe Database of Antimicrobial Activity and Structure of Peptides (DBAASP) is an open-access, comprehensive database containing information on amino acid sequences, chemical modifications, 3D structures, bioactivities and toxicities of peptides that possess antimicrobial properties. DBAASP is updated continuously, and at present, version 3.0 (DBAASP v3) contains &gt;15 700 entries (8000 more than the previous version), including &gt;14 500 monomers and nearly 400 homo- and hetero-multimers. Of the monomeric antimicrobial peptides (AMPs), &gt;12 000 are synthetic, about 2700 are ribosomally synthesized, and about 170 are non-ribosomally synthesized. Approximately 3/4 of the entries were added after the initial release of the database in 2014 reflecting the recent sharp increase in interest in AMPs. Despite the increased interest, adoption of peptide antimicrobials in clinical practice is still limited as a consequence of several factors including side effects, problems with bioavailability and high production costs. To assist in developing and optimizing de novo peptides with desired biological activities, DBAASP offers several tools including a sophisticated multifactor analysis of relevant physicochemical properties. Furthermore, DBAASP has implemented a structure modelling pipeline that automates the setup, execution and upload of molecular dynamics (MD) simulations of database peptides. At present, &gt;3200 peptides have been populated with MD trajectories and related analyses that are both viewable within the web browser and available for download. More than 400 DBAASP entries also have links to experimentally determined structures in the Protein Data Bank. DBAASP v3 is freely accessible at http://dbaasp.org.
Pediatric weight management, dietary restraint, dieting, and eating disorder risk: a systematic review
Authors: House Eve T , Gow Megan L , Lister Natalie B , Baur Louise A , Garnett Sarah P , Paxton Susan J , Jebeile Hiba 
Published: October 2020

AbstractContextWhether dietary restraint and dieting are risk factors associated with eating disorders has not been explored in the context of pediatric weight management.ObjectiveTo review associations between dietary pediatric weight management, dietary restraint, dieting, and eating disorder risk.Data sources, selection, and extractionFour databases – MEDLINE, EMBASE, Cochrane Library, and PsycINFO – were searched to May 2020 to identify pediatric weight management interventions with a dietary component for children and adolescents with overweight or obesity. The review was limited to studies reporting dietary restraint and/or dieting at preintervention, postintervention, and/or follow-up. Screening and quality assessment were conducted in duplicate, and data extraction was completed by 1 reviewer and cross-checked for accuracy. Data extracted included study characteristics, dietary restraint/dieting, and eating disorder–related outcomes (including disordered eating, body image, self-esteem, depression, and anxiety).ResultsA total of 26 papers, representing 23 studies, were included. Of these, 20 studies reported on dietary restraint, which increased (10 postintervention, 6 follow-up) or remained unchanged (7 postintervention, 5 follow-up), and 5 studies reported on dieting, which increased (1 study), remained unchanged (2 studies) or decreased (2 studies) postintervention. All studies that reported on other eating disorder risk factors (eg, binge eating, body dissatisfaction, and depression) and weight-related outcomes found improvement or no change postintervention or at follow-up.ConclusionThe results of this review suggest that current measures of dietary restraint and dieting are not associated with eating disorder risk within the context of pediatric weight management; however, long-term data is limited. In addition, those current measures may not be suitable risk markers. Concerns about dietary restraint and dieting leading to eating disorders should not prevent access to quality care for young people with obesity.Systematic Review RegistrationPROSPERO registration no. 2017 CRD42017069488.
Using Silica Activity to Model Redox-dependent Fluid Compositions in Serpentinites from 100 to 700 °C and from 1 to 20 kbar
Authors: Lazar Codi 
Published: October 2020

AbstractSerpentinization is a metamorphic process that can stabilize highly reduced hydrogen-rich fluids. Previous measurements of elevated CH4 and H2 concentrations in ultramafic-hosted submarine springs indicate that active serpentinization occurs along mid-ocean ridge systems at seafloor pressures (∼&lt;500 bar) and temperatures (∼&lt;350 °C). Serpentinites also exist at higher pressures in subduction zones; for example, during retrograde hydration of the forearc mantle wedge and during prograde deserpentinization within the subducted slab. However, many studies demonstrating the thermodynamic stability of reduced serpentinite fluids have been limited to terrestrial seafloor conditions. To investigate the redox state of serpentinite fluids at elevated pressures, phase equilibria and fluid compositions were computed for 100–700 °C and 1–20 kbar using aqueous silica activity (aSiO2(aq)) as a governing parameter. Silica-sensitive, redox-buffering assemblages were selected to be consistent with previously proposed reactions: SiO2(aq)–fayalite–magnetite (QFM), SiO2(aq)–Fe-brucite–cronstedtite, SiO2(aq)–Fe-brucite–Fe3+-serpentine, plus the silica-free buffer Fe-brucite–magnetite. Fluid species are limited to simple, zerovalent compounds. For silica-bearing redox reactions, aSiO2(aq) is buffered by coexisting ultramafic mineral assemblages in the system MgO–SiO2–H2O. Silica activity and fO2 are directly correlated, with the most reduced fluids stabilized by the least siliceous assemblages. Silica activity and fO2 increase with pressure, but are more strongly dependent on temperature, leading to greater silica enrichment and more oxidized conditions along shallow, warm subduction paths than along steeper, colder paths. Reduced fluids with mCH4/mCO2 &gt; 1 and fO2 below QFM are present only when serpentine is stable, and are favored along all subduction trajectories except shallow P–T paths at eclogite-grade. Values of mH2 and mCO/mCO2 depend strongly on P and T, but also on the choice of redox buffer, especially whether the Fe-serpentine component is cronstedtite or Fe3+-serpentine. Methane and H2S production are thermodynamically favored throughout the P–T range of the serpentinized forearc mantle and in other settings with similar conditions; for example, deep planetary seafloors. The model offers a generalized technique for estimating the redox state of a fluid-saturated serpentinite at elevated P and T, and yields results consistent with previous petrographic and thermodynamic analyses. High-pressure serpentinization may be an important source of reduced species that could influence prebiotic chemistry, support microbial life in the deep biosphere or in deep planetary oceans, or promote greenhouse warming on early Earth.
Acute Rehabilitation of a Patient With COVID-19 Myocarditis: A Case Report
Authors: Butler Kelly , Clancy Malachy J , Adler Joe , Tevald Michael A 
Published: October 2020

Abstract

Objective
The purpose of this case report is to describe the acute rehabilitation of an individual with severe COVID-19 complicated by myocarditis, focusing on both facility-wide and patient-specific strategies.

Methods
A 50-year-old male presented to the emergency department with progressive dyspnea and confirmed COVID-19. He developed hypoxic respiratory failure and heart failure requiring prolonged mechanical ventilation. Mobility was limited by severe impairments in strength, endurance, balance, and cognition. The referral, screening, and rehabilitation of this patient were guided by a COVID-19 Service Delivery Plan designed to maximize the effectiveness and efficiency of care delivery while minimizing staff exposure to the virus. Coordinated physical and occupational therapy sessions focused on progressive mobility and cognitive retraining. Progress was monitored using a series of standardized outcome measures, including the Activity Measure for Post-Acute Care, Timed Up and Go test, and the Saint Louis University Mental Status examination.

Results
Rehabilitation was initiated on day 18, and the patient participated in 19 treatment sessions, each approximately 30 minutes, over the remaining 30 days of his hospital stay. His Activity Measure for Post-Acute Care mobility and function scores both improved from 100% to 0% disability, he experienced substantial improvements in both Timed Up and Go (Δ = 4.2 seconds) and Saint Louis University Mental Status (discharge score = 25). There were no adverse events. He was discharged to home with his family and home rehabilitation services.

Conclusion
COVID-19 contributed to severe declines in mobility and function in this middle-aged man. He experienced substantial gains in his function, mobility, and cognition during his in-hospital rehabilitation, which was guided by a facility-wide plan to prevent virus transmission.

Impact
The rehabilitation of individuals with severe COVID-19 presents significant challenges, both at the level of the individual patient and the whole facility. This report describes clinical decision-making required to manage these individuals in the setting of a global pandemic.
Evaluation of Pragmatic Telehealth Physical Therapy Implementation During the COVID-19 Pandemic
Authors: Miller Matthew J , Pak Sang S , Keller Daniel R , Barnes Deborah E 
Published: October 2020

Abstract

Objective
The objective was to evaluate implementation of telehealth physical therapy in response to COVID-19 and identify implementation strategies to maintain and scale up telehealth physical therapy within a large urban academic medical center.

Methods
The Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework was used to evaluate telehealth physical therapy implementation. Patient-level data were extracted from electronic medical records between March 16, 2020, and May 16, 2020 (implementation phase). Reach was defined as the proportion of physical therapy sessions completed via telehealth. Effectiveness was assessed using a patient-reported satisfaction survey with a 5-point Likert scale. Adoption was defined as the proportion of physical therapists who used telehealth. Implementation was assessed through qualitative analysis of patient and clinician perspectives to identify emergent themes, retrospectively classify strategies used during the implementation phase, and prospectively identify evidence-based strategies to increase telehealth maintenance and scale-up. Maintenance of telehealth was defined as the proportion of patients who indicated they would attend another telehealth session.

Results
There were 4548 physical therapy sessions provided by 40 therapists from March 22, 2020, to May 16, 2020, of which 3883 (85%) were telehealth. Ninety-four percent of patients were satisfied. All physical therapists (100%) used telehealth technology at least once. Retrospectively classified and prospectively identified evidence-based strategies were organized into 5 qualitative themes that supported implementation: organizational factors (policies, preexisting partnerships), engaging external stakeholders (satisfaction survey), champions (clinician leaders), clinician education (dynamic, ongoing training), and process (promote adaptability, small tests of change). Ninety-two percent of patients reported they would attend another telehealth session.

Conclusion
Findings from this study suggest that implementation of telehealth physical therapy during the COVID-19 pandemic was feasible and acceptable in this setting.

Impact
These results can be used to guide future health policy, quality improvement, and implementation science initiatives to expand the use and study of telehealth for physical therapy.
Health services utilization and its determinants in the context of recession: evidence from Greece
Authors: Beletsioti Chrysoula , Niakas Dimitris 
Published: October 2020

Abstract

Background
In 2009, Greece entered a prolonged economic recession and adopted austerity reforms, which have profoundly affected many aspects of health sector, including health services use. The objective of this study was to investigate healthcare utilization in the Greek population in the context of austerity and its determinants.

Methods
Two National Health Surveys of the population aged 15 and over, conducted in 2009 and 2014—before and after the adoption of austerity measures—, were used to analyse possible changes in healthcare utilization and its determinants applying chi-square tests, Mann–Whitney U-tests and generalized linear models.

Results
Between 2009 and 2014, the share of those who had visited a specialist decreased, whereas that of those who had visited a general practitioner or had been hospitalized did not change significantly. The number of outpatient consultations decreased and the number of nights spent in hospital did not change significantly. The strongest predictors were self-rated health, presence of chronic diseases and experiencing pain.

Conclusions
Identifying the procyclical or counter-cyclical nature of healthcare utilization and the association between utilization and its determinants in different settings is an important priority in order to improve access and promote health equity.
The COVID-19 era: the view from Nigeria
Authors: Oleribe O O , Oskouipour P , Nwanyanwu O , Taylor-Robinson S D 
Published: October 2020

Abstract
If we were told that one day the entire world would take its guidance for managing a health crisis from empirical thought, nobody would have believed it. However, with the December 2019 arrival of COVID-19 in China, the world subsequently went into a frenzied state that resulted in the widespread adoption of untested strategies or potential cures; circumstantial evidence provided without randomized control trials (RCTs) was published rapidly and widely considered the gold standard in medical research and therapeutics. Nigeria and much of the rest of the world blindly adopted treatments like chloroquine or hydroxychloroquine and various prevention strategies, often without monitoring the efficacy of these treatment and social control strategies. COVID-19 provided Nigeria a critical opportunity to create or strengthen its national laboratory system by building up its Level 3 laboratories in all parts of the country with the capability to perform PCR tests and viral isolation. There was also an opportunity to establish hospitals in every region of a sufficient standard to reduce the numbers of Nigerians travelling abroad to seek medical treatment; to invest in building capacity to develop antiviral medications and vaccines in Nigeria, and to ensure better international health policies. Rather, Nigerian leaders, government and health managers decided (like most other nations of the world) to shut down the society using isolationist policies that were not necessarily tailored to local needs. Despite adopting these methods, COVID-19 cases continued to skyrocket in Nigeria. In the future, before adopting such broad sweeping policies, there should be local tailoring to assess their effectiveness in different communities. Given that the country has much experience in controlling Lassa and Marburg Fever outbreaks, Nigeria should lead by developing new strategies, new protocols and new local guidelines, based on validated and reproducible studies to ensure that the public health authorities are not caught unaware by any new outbreaks of emerging or remerging diseases.
Longitudinal changes in cerebral white matter microstructure in newly diagnosed systemic lupus erythematosus patients
Authors: Silvagni Ettore , Inglese Francesca , Bortoluzzi Alessandra , Borrelli Massimo , Goeman Jelle J , Revenaz Alfredo , Groppo Elisabetta , Steup-Beekman Gerda M , Huizinga Tom W J , Ronen Itamar , de Bresser Jeroen , Fainardi Enrico , Govoni Marcello , Ercan Ece 
Published: October 2020

Abstract

Objectives
To evaluate longitudinal variations in diffusion tensor imaging (DTI) metrics of different white matter (WM) tracts of newly diagnosed SLE patients, and to assess whether DTI changes relate to changes in clinical characteristics over time.

Methods
A total of 17 newly diagnosed SLE patients (19–55 years) were assessed within 24 months from diagnosis with brain MRI (1.5 T Philips Achieva) at baseline, and after at least 12 months. Fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity values were calculated in several normal-appearing WM tracts. Longitudinal variations in DTI metrics were analysed by repeated measures analysis of variance. DTI changes were separately assessed for 21 WM tracts. Associations between longitudinal alterations of DTI metrics and clinical variables (SLEDAI-2K, complement levels, glucocorticoid dosage) were evaluated using adjusted Spearman correlation analysis.

Results
Mean MD and RD values from the normal-appearing WM significantly increased over time (P = 0.019 and P = 0.021, respectively). A significant increase in RD (P = 0.005) and MD (P = 0.012) was found in the left posterior limb of the internal capsule; RD significantly increased in the left retro-lenticular part of the internal capsule (P = 0.013), and fractional anisotropy significantly decreased in the left corticospinal tract (P = 0.029). No significant correlation was found between the longitudinal change in DTI metrics and the change in clinical measures.

Conclusion
Increase in diffusivity, reflecting a compromised WM tissue microstructure, starts in initial phases of the SLE disease course, even in the absence of overt neuropsychiatric (NP) symptoms. These results indicate the importance of monitoring NP involvement in SLE, even shortly after diagnosis.
Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy
Authors: Bogan Richard K , Thorpy Michael J , Dauvilliers Yves , Partinen Markku , Del Rio Villegas Rafael , Foldvary-Schaefer Nancy , Skowronski Roman , Tang Lihua , Skobieranda Franck , Šonka Karel 
Published: October 2020

AbstractStudy ObjectivesEvaluate efficacy and safety of lower-sodium oxybate (LXB), a novel oxybate medication with 92% less sodium than sodium oxybate (SXB).MethodsAdults aged 18–70 years with narcolepsy with cataplexy were eligible. The study included a ≤30-day screening period; a 12-week, open-label, optimized treatment and titration period to transition to LXB from previous medications for the treatment of cataplexy; a 2-week stable-dose period (SDP); a 2-week, double-blind, randomized withdrawal period (DBRWP); and a 2-week safety follow-up. During DBRWP, participants were randomized 1:1 to placebo or to continue LXB treatment.ResultsEfficacy was assessed in 134 participants who received randomized treatment, and safety was assessed in all enrolled participants (N = 201). Statistically significant worsening of symptoms was observed in participants randomized to placebo, with median (first quartile [Q1], third quartile [Q3]) change in weekly number of cataplexy attacks from SDP to DBRWP (primary efficacy endpoint) in the placebo group of 2.35 (0.00, 11.61) versus 0.00 (−0.49, 1.75) in the LXB group (p &lt; 0.0001; mean [standard deviation, SD] change: 11.46 [24.751] vs 0.12 [5.772]), and median (Q1, Q3) change in Epworth Sleepiness Scale score (key secondary efficacy endpoint) of 2.0 (0.0, 5.0) in the placebo group versus 0.0 (−1.0, 1.0) in the LXB group (p &lt; 0.0001; mean [SD] change: 3.0 [4.68] vs 0.0 [2.90]). The most common treatment-emergent adverse events with LXB were headache (20.4%), nausea (12.9%), and dizziness (10.4%).ConclusionsEfficacy of LXB for the treatment of cataplexy and excessive daytime sleepiness was demonstrated. The safety profile of LXB was consistent with SXB.Clinical trial registrationNCT03030599.