bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE
Authors: Seo Go Hun , Kim Taeho , Choi In Hee , Park Jung‐young , Lee Jungsul , Kim Sehwan , Won Dhong‐gun , Oh Arum , Lee Yena , Choi Jeongmin , Lee Hajeong , Kang Hee Gyung , Cho Hee Yeon , Cho Min Hyun , Kim Yoon Jeon , Yoon Young Hee , Eun Baik‐Lin , Desnick Robert J. , Keum Changwon , Lee Beom Hee 
Published: September 2020

AbstractEVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0‐68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield.
Linking patterns of intraspecific morphology to changing climates
Authors: McGuire Jenny L. , Lauer Daniel A. 
Published: September 2020

AbstractAimThis study examines how climate shaped Microtus californicus (Rodentia: Arvicolinae) ecomorphology throughout the Quaternary. It tests three hypotheses: (a) climate corresponds with consistent shape variation in M. californicus dentition; (b) Quaternary warming and drying trends caused M. californicus morphotypes to predictably shift in range through time and (c) Quaternary warming and drying led to predictable changes in tooth morphological variation. Finally, we discuss how shifts in climate‐linked morphological variation may affect the potential of M. californicus to react to future climate change.LocationWestern United States.TaxonMicrotus californicus (Peale, 1848).MethodsGeometric morphometrics and partial least squares analyses were used to discern how climate contributes to consistent variation in the shapes of the M. californicus lower first molar (m1), validated for the full toothrow. We further corroborate this relationship, reconstructing precipitation at fossil localities using m1 morphology and comparing those values to palaeoclimate‐model‐derived precipitations. Disparity analyses and a MANOVA were performed to examine changes in variation and whether a shift in tooth shape occurred through time.ResultsMicrotus californicus m1 and toothrow shapes are narrower and more curved in cooler, wetter climates. Morphology‐based palaeoclimate reconstructions align with model‐based palaeoclimate estimations. When time averaging is accounted for, M. californicus demonstrates a 12% reduction in variation from fossil to present‐day specimens, and these changes in tooth shape correspond with climate‐related morphotypes.Main conclusionsAs California became drier and hotter since the late Pleistocene, M. californicus dental morphology generally tracked these changes by adapting to the consumption of rougher vegetation in drier environments. This resulted in the loss of some high‐precipitation morphotypes, indicating that ecomorphology, often observed at the species and community levels, translates to intraspecific variation and dynamically changes in response to changing climates. The loss of climate‐linked morphological variation since the late Pleistocene may limit the ability of M. californicus to respond to future changes in climate. These findings portend that other species may have experienced similar losses in adaptability.
Bicuculline regulated protein synthesis is dependent on Homer1 and promotes its interaction with eEF2K through mTORC1‐dependent phosphorylation
Authors: Gladulich Luis F. H. , Xie Jianling , Jensen Kirk B. , Kamei Makoto , Paes‐de‐Carvalho Roberto , Cossenza Marcelo , Proud Christopher G. 
Published: September 2020

AbstractThe regulation of protein synthesis is a vital and finely tuned process in cellular physiology. In neurons, this process is very precisely regulated, as which mRNAs undergo translation is highly dependent on context. One of the most prominent regulators of protein synthesis is the enzyme eukaryotic elongation factor kinase 2 (eEF2K) that regulates the elongation stage of protein synthesis. This kinase and its substrate, eukaryotic elongation factor 2 (eEF2) are important in processes such as neuronal development and synaptic plasticity. eEF2K is regulated by multiple mechanisms including Ca2+‐ions and the mTORC1 signaling pathway, both of which play key roles in neurological processes such as learning and memory. In such settings, the localized control of protein synthesis is of crucial importance. In this work, we sought to investigate how the localization of eEF2K is controlled and the impact of this on protein synthesis in neuronal cells. In this study, we used both SH‐SY5Y neuroblastoma cells and mouse cortical neurons, and pharmacologically and/or genetic approaches to modify eEF2K function. We show that eEF2K activity and localization can be regulated by its binding partner Homer1b/c, a scaffolding protein known for its participation in calcium‐regulated signaling pathways. Furthermore, our results indicate that this interaction is regulated by the mTORC1 pathway, through a known phosphorylation site in eEF2K (S396), and that it affects rates of localized protein synthesis at synapses depending on the presence or absence of this scaffolding protein.
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The efficiency of voluntary risk classification in insurance markets
Authors: Crocker Keith J. , Zhu Nan 
Published: September 2020

AbstractIt has been established that categorical discrimination based on observable characteristics such as gender, age, or ethnicity enhances efficiency. We consider a different form of risk classification when there exists a costless yet imperfectly informative test of risk type, with the test outcome unknown to the agents ex ante. We show that a voluntary risk classification in which agents are given the option to take the test always increases efficiency compared with no risk classification. Moreover, voluntary risk classification also Pareto dominates a regime of compulsory risk classification in which all agents are required to take the test.
Priority setting: Consensus for Australia's infant safe sleeping public health promotion programme
Authors: Cole Roni , Young Jeanine , Kearney Lauren , Thompson John MD 
Published: September 2020

AimTo develop focused priorities to inform the revision of Australia's Sudden Unexpected Death in Infancy (SUDI) risk reduction public health programme.MethodsA content expert consensus research activity was designed using two consensus techniques. The two‐phase study employed a Delphi process (phase 1) and a Nominal Group workshop technique (phase 2). The Delphi invited 56 national and international content experts. The Nominal Group comprised 17 Australasian experts and stakeholders to ensure priority setting was relevant to the Australian context.ResultsPhase 1 established a ranked thematic list of 10 key SUDI risk reduction themes. Phase 2 addressed three nominal questions producing prioritised lists for: key‐message wording; contextual information and strategies to support caregiver implementation of key messages; and considerations in redesigning and dissemination of a safe sleep campaign. The top four priority themes were: sleep position, sleep space, smoking and surface‐sharing.ConclusionThis two‐phase priority setting was successful in establishing clearly defined infant safe sleep priorities. International content expert participation in phase 1 strengthened priority setting outcomes while phase 2 ensured final outcomes provided a strong national focus reflective of identified needs of Australian families. Findings provide a foundation from which important components can be considered when revising and developing future SUDI risk reduction programmes.
A quality improvement project to improve the identification and management of delirium
Authors: Sutton‐Smith Lynsey 
Published: September 2020

AbstractBackgroundEfforts to reduce delirium burden through screening, identification, and prevention is considered one of the major public health priorities of the last decade. In 2017, an audit of delirium screening in our unit revealed suboptimum assessment of our patients, with compliance with the Confusion Assessment Method for the ICU (CAM‐ICU) assessments highly variable and ad hoc, and sometimes not at all. A separate sedation audit also revealed that our sedation practices did not align with current critical care guidelines emphasizing light sedation strategies.AimThe aim of this project was to develop resources to educate the unit on delirium, improve the management of sedation with a sedation algorithm, formalize the elements of delirium prevention and care into a delirium pathway, and improve the compliance with delirium screening.MethodsWe developed a delirium clinical pathway and sedation algorithm, a delirium resource book, and an online educational module on the district health board (DHB) intranet. We provided extensive teaching of all these resources over delirium month. We used pre‐ and post‐auditing of sedation practices and delirium screening compliance to inform the success of this project.ResultsOf the 140 members of staff, 85% (n = 120) received delirium education. In 2018/2019, 84% of 145 patient charts reached the unit standard of four to six hourly CAM‐ICU assessments compared with 45% in 2017. The sedation audit revealed a slight improvement in the trend towards lighter sedation, with Richmond Agitation Sedation Scoring (RASS) scores reflecting light sedation, increasing from a mean of 31% in 2017 to 41% in 2019 from 41 patient charts.ConclusionsThis project provides a useful framework to enable future quality improvement work around delirium and sedation management. The clinical pathway and sedation algorithm have been a useful tool to introduce to the unit as a way of formalizing the elements of delirium care and assessment.
What exercise prescription is optimal to improve body composition and cardiorespiratory fitness in adults living with obesity? A network meta‐analysis
Authors: O'Donoghue Grainne , Blake Catherine , Cunningham Caitriona , Lennon Olive , Perrotta Carla 
Published: September 2020

SummaryCurrent international guidelines recommend people living with obesity should be prescribed a minimum of 300 min of moderately intense activity per week for weight loss. However, the most efficacious exercise prescription to improve anthropometry, cardiorespiratory fitness (CRF) and metabolic health in this population remains unknown. Thus, this network meta‐analysis was conducted to assess and rank comparative efficacy of different exercise interventions on anthropometry, CRF and other metabolic risk factors. Five electronic databases were searched for randomized controlled trials (RCTs) that compared different exercise modalities to improve anthropometry, CRF and/or metabolic health in adults living with obesity. RCTs were evaluated using the Cochrane risk of bias tool. A random effects network meta‐analysis was performed within a frequentist framework. Of the 6663 articles retrieved, 45 studies with a total 3566 participants were included. Results reveal that while any type of exercise intervention is more effective than control, weight loss induced is modest. Interventions that combine high‐intensity aerobic and high‐load resistance training exert beneficial effects that are superior to any other exercise modality at decreasing abdominal adiposity, improving lean body mass and increasing CRF. Clinicians should consider this evidence when prescribing exercise for adults living with obesity, to ensure optimal effectiveness.
Gram Staining: a Comparison of Two Automated Systems and Manual Staining
Authors: Froböse Neele J. , Bjedov Sara , Schuler Franziska , Kahl Barbara C. , Kampmeier Stefanie , Schaumburg Frieder 
Published: September 2020

Various Gram staining automated systems are available to accelerate and standardize the staining process, but a systematic comparison of different systems is largely lacking. The objective of this study was to evaluate two devices in comparison to manual Gram staining. Clinical samples (
n
= 500; University Hospital Münster, Germany; May to June 2020) were simultaneously Gram stained manually and with two automated Gram stainers (Previ Color Gram, bioMérieux, and ColorAX2, Axonlab).
Investigation of predictors of interest in a brief mindfulness-based intervention and its effects in patients with psoriasis at a rehabilitation clinic (SkinMind): an observational study and randomised controlled trial
Authors: Stadtmüller Laura , Eckardt Markus , Zick Christoph , Kupfer Joerg , Schut Christina 
Published: September 2020

IntroductionPsoriasis (PS) is a chronic inflammatory skin disease accompanied by reduced quality of life. Mindfulness is the ability to focus on the present moment without evaluation. Findings on the effects of 8-week mindfulness trainings in patients with PS reveal positive effects on the severity of the disease and quality of life. However, it remained unclear what distinguishes patients with PS interested in psychological interventions from those without interest and whether also a shorter, namely 2-week mindfulness-based intervention is beneficial in this patient group. This will be investigated with this study.Methods and analysesData will be collected at a rehabilitation clinic in Germany. The study is divided into two parts: study 1a is an observational study. Its aim is to investigate whether sociodemographic, skin-related and psychological factors are significant predictors of interest in a brief psychological intervention in 127 patients with PS. Study 1b is a randomised controlled trial, in which 60 patients (retrieved from study 1a) will be randomised to an intervention or control group (treatment as usual). The main outcome variables are mindfulness and self-compassion. In addition, mediation analyses will be used in an explorative manner to test whether there is a relationship between mindfulness/self-compassion and the severity of PS and whether it is mediated by itch catastrophising and fear of negative evaluation (first model) or perceived stress (second model).Ethics and disseminationThe study protocol has been approved by the University of Giessen. Study results will be disseminated by publication of the results at (inter) national conferences and in scientific journals.Trial registration numbersDRKS00017426 and DRKS00017429.
Scoping review protocol on non-pharmacological interventions for interpersonal and self-directed violence in adults with severe mental illness
Authors: Moreno-Calvete Maria Concepcion , Ruiz-Ibañez Ivan , Uriarte-Uriarte Jose Juan 
Published: September 2020

IntroductionViolence committed by people with mental illness has implications for mental health policy and clinical practice. Several strategies to reduce the risk of aggressive and violent behaviour have been proposed, and these include non-pharmacological interventions. There is, however, a need to identify which of these interventions are effective, and as a first step, we will conduct a scoping review to identify non-pharmacological interventions for self-directed or interpersonal violence in adults with severe mental illness across different conditions and settings.Methods and analysisThis is a scoping review protocol. The review will include any randomised controlled trials (RCTs) and cluster RCTs that assess the efficacy of interventions on self-directed or interpersonal violence with no restrictions on the control treatment in people with severe mental illness in any setting. No restrictions will be applied in terms of language or date of publication. To identify studies, a search will be performed in the following databases: Embase, MEDLINE (via PubMed), PsycINFO, CINAHL, LILACS, SciELO, Cochrane Library, Web of Science, Scopus, ProQuest, Epistemonikos and databases of clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement will be followed for reporting the findings, including the use of a PRISMA flow diagram. A standardised form will be used to extract data from studies. The findings will be classified using conceptual categories that will be specified in detail and a descriptive summary of the main results will be created. Moreover, it will be assessed whether the studies identified have been included in systematic reviews or meta-analyses and the results will be used to generate a conceptual map.Ethics and disseminationNo patients or other participants will be involved in this study. We will prepare a manuscript for publication in a peer-reviewed journal and the results will be presented at mental health conferences.
End-tidal and arterial carbon dioxide gradient in serious traumatic brain injury after prehospital emergency anaesthesia: a retrospective observational study
Authors: Price James , Sandbach Daniel D , Ercole Ari , Wilson Alastair , Barnard Ed Benjamin Graham 
Published: September 2020

ObjectivesIn the UK, 20% of patients with severe traumatic brain injury (TBI) receive prehospital emergency anaesthesia (PHEA). Current guidance recommends an end-tidal carbon dioxide (ETCO2) of 4.0–4.5 kPa (30.0–33.8 mm Hg) to achieve a low-normal arterial partial pressure of CO2(PaCO2), and reduce secondary brain injury. This recommendation assumes a 0.5 kPa (3.8 mm Hg) ETCO2–PaCO2gradient. However, the gradient in the acute phase of TBI is unknown. The primary aim was to report the ETCO2–PaCO2gradient of TBI patients at hospital arrival.MethodsA retrospective cohort study of adult patients with serious TBI, who received a PHEA by a prehospital critical care team in the East of England between 1 April 2015 and 31 December 2017. Linear regression was performed to test for correlation and reported as R-squared (R2). A Bland-Altman plot was used to test for paired ETCO2and PaCO2agreement and reported with 95% CI. ETCO2–PaCO2gradient data were compared with a two-tailed, unpaired, t-test.Results107 patients were eligible for inclusion. Sixty-seven patients did not receive a PaCO2sample within 30 min of hospital arrival and were therefore excluded. Forty patients had complete data and were included in the final analysis; per protocol. The mean ETCO2–PaCO2gradient was 1.7 (±1.0) kPa (12.8 mm Hg), with moderate correlation (R2=0.23, p=0.002). The Bland-Altman bias was 1.7 (95% CI 1.4 to 2.0) kPa with upper and lower limits of agreement of 3.6 (95% CI 3.0 to 4.1) kPa and −0.2 (95% CI −0.8 to 0.3) kPa, respectively. There was no evidence of a larger gradient in more severe TBI (p=0.29). There was no significant gradient correlation in patients with a coexisting serious thoracic injury (R2=0.13, p=0.10), and this cohort had a larger ETCO2–PaCO2gradient, 2.0 (±1.1) kPa (15.1 mm Hg), p=0.01. Patients who underwent prehospital arterial blood sampling had an arrival PaCO2of 4.7 (±0.2) kPa (35.1 mm Hg).ConclusionThere is only moderate correlation of ETCO2and PaCO2at hospital arrival in patients with serious TBI. The mean ETCO2–PaCO2gradient was 1.7 (±1.0) kPa (12.8 mm Hg). Lower ETCO2targets than previously recommended may be safe and appropriate, and there may be a role for prehospital PaCO2measurement.
Multicentric evaluation of analytical performances digital morphology with respect to the reference methods by manual optical microscopy
Authors: Da Rin Giorgio , Benegiamo Anna , Di Fabio Anna Maria , Dima Francesco , Francione Sara , Fanelli Alessandra , Germagnoli Luca , Lorubbio Maria , Marzoni Alessandro , Pajola Rachele , Pipitone Silvia , Rolla Roberta , Seghezzi Michela , Baigorria Vaca Maria del Carmen , Bartolini Andrea , Buoro Sabrina 
Published: September 2020

AimsOptical microscopic (OM) evaluation of peripheral blood (PB) cells is still a crucial step of the laboratory haematological workflow. The morphological cell analysis is time-consuming and expensive and it requires skilled operator. To address these challenges, automated image-processing systems, as digital morphology (DM), were developed in the last few years. The aim of this multicentre study, performed according to international guidelines, is to verify the analytical performance of DM compared with manual OM, the reference method.MethodsFour hundred and ninety PB samples were evaluated. For each sample, two May Grunwald-stained and Giemsa-stained smears were performed and the morphological evaluation of cells was analysed with both DM and OM. In addition, the assessment times of both methods were recorded.ResultsComparison of DM versus OM methods was assessed with Passing-Bablok and Deming fit regression analysis: slopes ranged between 0.17 for atypical, reactive lymphocytes and plasma cells (LY(AT)) and 1.24 for basophils, and the intercepts ranged between −0.09 for blasts and 0.40 for LY(AT). The Bland-Altman bias ranged between −6.5% for eosinophils and 21.8% for meta-myemielocytes. The diagnostic agreement between the two methods was 0.98. The mean of assessment times were 150 s and 250 s for DM and OM, respectively.ConclusionDM shows excellent performance. Approximately only 1.6% of PB smears need the OM revision, giving advantages in terms of efficiency, standardisation and assessment time of morphological analysis of the cells. The findings of this study may provide useful information regarding the use of DM to improve the haematological workflow.