bluuebunny/crossref_metadata_2025_split huggingface dataset:
High transient stress in the lower crust: Evidence from dry pseudotachylytes in granulites, Lofoten Archipelago, northern Norway
Authors: Dunkel Kristina G. , Zhong Xin , Arnestad Paal Ferdinand , Valen Lars Vesterager , Jamtveit Bjørn 
Published: September 2020

AbstractSeismic activity below the standard seismogenic zone is difficult to investigate because the geological records of such earthquakes, pseudotachylytes, are typically reacted and/or deformed. Here, we describe unusually pristine pseudotachylytes in lower-crustal granulites from the Lofoten Archipelago, northern Norway. The pseudotachylytes have essentially the same mineralogical composition as their host (mainly plagioclase, alkali feldspar, orthopyroxene) and contain microstructures indicative of rapid cooling, i.e., feldspar microlites and spherulites and “cauliflower” garnets. Mylonites are absent, both in the wall rocks and among the pseudotachylyte clasts. The absence of features recording precursory ductile deformation rules out several commonly invoked mechanisms for triggering earthquakes in the lower crust, including thermal runaway, plastic instabilities, and downward propagation of seismic slip from the brittle to the ductile part of a fault. The anhydrous mineralogy of host and pseudotachylytes excludes dehydration-induced embrittlement. In the absence of such weakening mechanisms, stress levels in the lower crust must have been transiently high.
Factors associated with quality of life and work ability among Finnish municipal employees: a cross-sectional study
Authors: Bergman Elina , Löyttyniemi Eliisa , Myllyntausta Saana , Rautava Päivi , Korhonen Päivi Elina 
Published: September 2020

ObjectivesQuality of life (QoL) and work ability are elementary parts in defining the well-being of an employed person. The aim of this study was to demonstrate factors associated with QoL and self-reported work ability among public sector employees, while taking into account several confounding factors, including sleep quality, occupational stress and psychological symptoms.MethodsA cross-sectional study was conducted in Finland among 710 employees (89% women, mean age 49 (SD=10) years) from 10 municipal work units in 2015. Information about the participants was collected by physical examination, self-administered questionnaire and from medical history. QoL was assessed with the EUROHIS-Quality of Life 8-item index and work ability with the Work Ability Score (WAS).ResultsThe EUROHIS-QOL mean score among all participants was 4.07 (95% CI 4.03 to 4.11). QoL was positively associated with good sleep quality, cohabiting, university-level education and lower body mass index (BMI), and negatively associated with occupational stress, depression and/or anxiety and disease burden. Work ability was reported good or excellent by 80% of the participants and the WAS mean score among all participants was 8.31 (95% CI 8.21 to 8.41). Work ability was positively associated with good sleep quality, younger age, lower BMI and university-level education, and negatively associated with occupational stress and disease burden.ConclusionsOccupational stress and self-reported sleep quality were strongly associated with both QoL and work ability among Finnish public sector employees. These findings highlight the need for screening and handling of work stress and sleep problems in occupational and primary healthcare.
Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands
Authors: Smit Lisa , Trogrlić Zoran , Devlin John W , Osse Robert-Jan , Ponssen Huibert H , Slooter Arjen J C , Hunfeld Nicole G M , Rietdijk Wim J R , Gommers Diederik , van der Jagt Mathieu 
Published: September 2020

IntroductionDelirium in critically ill adults is associated with prolonged hospital stay, increased mortality and greater cognitive and functional decline. Current practice guideline recommendations advocate the use of non-pharmacological strategies to reduce delirium. The routine use of scheduled haloperidol to treat delirium is not recommended given a lack of evidence regarding its ability to resolve delirium nor improve relevant short-term and longer-term outcomes. This study aims to evaluate the efficacy and safety of haloperidol for the treatment of delirium in adult critically ill patients to reduce days spent with coma or delirium.Methods and analysisEuRIDICE is a prospective, multi-centre, randomised, double-blind, placebo-controlled trial. Study population consists of adult intensive care unit (ICU) patients without acute neurological injury who have delirium based on a positive Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method for the ICU (CAM-ICU) assessment. Intervention is intravenous haloperidol 2.5 mg (or matching placebo) every 8 hours, titrated daily based on ICDSC or CAM-ICU positivity to a maximum of 5 mg every 8 hours, until delirium resolution or ICU discharge. Main study endpoint is delirium and coma-free days (DCFD) up to 14 days after randomisation. Secondary endpoints include (1) 28-day and 1-year mortality, (2) cognitive and functional performance at 3 and 12 months, (3) patient and family delirium and ICU experience, (4) psychological sequelae during and after ICU stay, (4) safety concerns associated with haloperidol use and (5) cost-effectiveness. Differences in DCFDs between haloperidol and placebo group will be analysed using Poisson regression analysis. Study recruitment started in February 2018 and continues.Ethics and disseminationThe study has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam (MEC2017-511) and by the Institutional Review Boards of the participating sites. Its results will be disseminated via peer-reviewed publication and conference presentations.Trial registrationNCT03628391
Integrated communication support program for oncologists, caregivers and patients with rapidly progressing advanced cancer to promote patient-centered communication: J-SUPPORT 1904 study protocol for a randomised controlled trial
Authors: Fujimori Maiko , Sato Ayako , Jinno Sayaka , Okusaka Takuji , Yamaguchi Takuhiro , Ikeda Masafumi , Ueno Makoto , Ozaka Masato , Takayama Yukiko , Miyaji Tempei , Majima Yoshiyuki , Uchitomi Yosuke 
Published: September 2020

IntroductionCommunication is an essential aspect of care for patients with progressive serious illnesses. This study aims to evaluate the efficacy of a new, integrated communication support program for oncologists, patients with rapidly progressing advanced cancer and their caregivers.Methods and analysisThe proposed integrated communication support programme is in the randomised control trial stage. It comprises a cluster of oncologists from comprehensive cancer centre hospitals in a metropolitan area in Japan. A total of 20 oncologists, 200 patients with advanced pancreatic cancer and the patients’ caregivers are enrolled in this study as of the writing of this protocol report. Oncologists are randomly assigned to the intervention group (IG) or control group (CG). Patients and caregivers are allocated to the same group as their oncologists. The IG oncologists receive a 2.5-hour individual communication skills training, and patients and caregivers receive a half-hour coaching intervention to facilitate prioritising and discussing questions and concerns; the CG participants do not receive any training. Follow-up data will be collected quarterly for 6 months for a year and then annually for up to 3 years. The primary endpoint is the intergroup difference between before-intervention and after-intervention patient-centred communication behaviours during oncology visits.Ethics and disseminationThis study is conducted in accordance with the ethical guidelines for clinical studies published by Japan’s Ministry of Education, Cultural, Sports, Science and Technology, the Ministry of Health, Labour and Welfare, and the ethical principles established for research on humans stipulated in the Declaration of Helsinki and further amendments thereto. The protocol was approved by the Institutional Review Board of National Cancer Center, Japan on 4 July 2018 (ID: 2017-474).Trial statusThis study is currently enrolling participants. Enrolment period ends 31 July 2020; estimated follow-up date is 31 March 2023.Trial registration numberUMIN Clinical Trial Registry (UMIN000033612); pre-results.
In out-of-hospital cardiac arrest, is the positioning of victims by bystanders adequate for CPR? A cohort study
Authors: Wagner Patrick , Schloesser Sebastian , Braun Julia , Arntz Hans-Richard , Breckwoldt Jan 
Published: September 2020

ObjectivesOutcome from out-of-hospital cardiac arrest (OHCA) highly depends on bystander cardiopulmonary resuscitation (CPR) with high-quality chest compressions (CCs). Precondition is a supine position of the victim on a firm surface. Until now, no study has systematically analysed whether bystanders of OHCA apply appropriate positions to victims and whether the position is associated with a particular outcome.DesignProspective observational cohort study.SettingMetropolitan emergency medical services (EMS) serving a population of 400 000; dispatcher-assisted CPR was implemented. We obtained information from the first EMS vehicle arriving on scene and matched this with data from semi-structured interviews with witnesses of the arrest.ParticipantsBystanders of all OHCAs occurring during a 12-month period (July 2006–July 2007). From 201 eligible missions, 200 missions were fully reported by EMS. Data from 138 bystander interviews were included.Primary and secondary outcome measuresProportion of positions suitable for effective CCs; related survival with favourable neurological outcome at 3 months.ResultsPositioning of victims at EMS arrival was ‘supine on firm surface’ in 64 cases (32.0%), ‘recovery position (RP)’ in 37 cases (18.5%) and other positions unsuitable for CCs in 99 cases (49.5%). Survival with favourable outcome at 3 months was 17.2% when ‘supine position’ had been applied, 13.5% with ‘RP’ and 6.1% with ‘other positions unsuitable for CCs’; a statistically significant association could not be shown (p=0.740, Fisher’s exact test). However, after ‘effective CCs’ favourable outcome at 3 months was 32.0% compared with 5.3% if no actions were taken. The OR was 5.87 (p=0.02).ConclusionIn OHCA, two-thirds of all victims were found in positions not suitable for effective CCs. This was associated with inferior outcomes. A substantial proportion of the victims was placed in RP. More attention should be paid to the correct positioning of victims in OHCA. This applies to CPR training for laypersons and dispatcher-assisted CPR.
Role of perceived neighbourhood crime in the longitudinal association between perceived built environment and type 2 diabetes mellitus: a moderated mediation analysis
Authors: Dendup Tashi , Feng Xiaoqi , O’Shaughnessy P. Y. , Astell-Burt Thomas 
Published: September 2020

BackgroundWe examined to what extent perceived neighbourhood crime moderates, associations between type 2 diabetes mellitus (T2DM) and perceived local amenities, recreational facilities, footpaths and public transit, and potential mediation of environmental characteristics—T2DM association by physical activity, social contact, sleep and body mass index (BMI).MethodsThe 45 and Up Study data of 36, 224 individuals collected from 2010 to 2015 were analysed in 2019 using multilevel logistic regression to examine the association between T2DM and clustering of unfavourable built environment, and any difference in the association with increasing unfavourable environment and area disadvantage. We performed causal mediation analyses stratified by crime to examine whether crime moderated the strength of identified local amenities–T2DM pathways.ResultsThe results showed that irrespective of crime, perceived lack of local amenities was associated with increased odds of developing T2DM, and BMI mediated 40% and 30.3% of this association among those who reported unsafe and safe daytime crime, respectively. The proportion mediated by BMI among those who reported unsafe and safe night-time crime was 27.3% and 35.1%, respectively. Walking mediated 5.7% of the local amenities–T2DM association among those who reported safe daytime crime. The odds of T2DM increased with rising unfavourable environment and area disadvantage.ConclusionsThe results suggest that the availability of neighbourhood amenities may lower T2DM risk by increasing walking and reducing BMI regardless of area crime. Policies to enhance access to local amenities and prevent crime, especially in disadvantaged areas, may support healthy behaviour and physical health that can potentially reduce T2DM risk.
Peripheral immunophenotype in dementia with Lewy bodies and Alzheimer’s disease: an observational clinical study
Authors: Amin Jay , Boche Delphine , Clough Zoe , Teeling Jessica , Williams Anthony , Gao Yifang , Chudley Lindsey , Lau Laurie , Smith Florence , Harris Scott , Holmes Clive 
Published: September 2020

BackgroundInflammation plays a key role in the aetiology and progression of Alzheimer’s disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly. We hypothesised that, using blood biomarkers, DLB would show an increased proinflammatory profile compared with controls, and that there would be a distinct profile compared with AD.Methods93 participants (31 with DLB, 31 with AD and 31 healthy older controls) completed a single study visit for neuropsychiatric testing and phlebotomy. Peripheral blood mononuclear cells were quantified for T and B cell subsets using flow cytometry, and serum cytokine concentrations were measured using multiplex immunoassay.ResultsWe detected reduced relative numbers of helper T cells and reduced activation of B cells in DLB compared with AD. Additionally, interleukin (IL)-1β was detected more frequently in DLB and the serum concentration of IL-6 was increased compared with controls.ConclusionsPeripheral inflammation is altered in DLB compared with AD, with T cell subset analysis supporting a possible shift towards senescence of the adaptive immune system in DLB. Furthermore, there is a proinflammatory signature of serum cytokines in DLB. Identification of this unique peripheral immunophenotype in DLB could guide development of an immune-based biomarker and direct future work exploring potential immune modulation as a novel treatment.
The thermal properties of the Mercia Mudstone Group
Authors: Parkes Dan , Busby Jon , Kemp Simon J. , Petitclerc Estelle , Mounteney Ian 
Published: September 2020

The Mercia Mudstone Group (MMG) crops out extensively across England and Wales and its thermal properties are required for the design of infrastructure such as ground source heating and cooling schemes and electrical cable conduits. Data from the literature and new data from a borehole core have been compiled to generate an updated range of thermal conductivities related to rock type and the lithostratigraphy. These indicate a total range in saturated vertical thermal conductivity of 1.67–3.24 W m
−1
K
−1
, comprising 1.67–2.81 W m
−1
K
−1
for mudstones, 2.12–2.41 W m
−1
K
−1
for siltstones and 2.3–3.24 W m
−1
K
−1
for sandstones. These data are all from measurements on samples and there will be uncertainty when considering the thermal properties of the rock mass owing to micro- and macrostructural features. Geometric mean modelling of thermal conductivity based on mineralogy has overestimated the thermal conductivity. Correction factors for the modelled thermal conductivities have been calculated to allow a first estimate of MMG thermal conductivities when only mineralogical data are available. Measured thermal diffusivities from the borehole core were in the range of 0.63–3.07 × 10
−6
m
2
s
−1
and are the first measured thermal diffusivities to be reported for the MMG.
Idelalisib Rescues Natural Killer Cells from Monocyte-Induced Immunosuppression by Inhibiting NOX2-Derived Reactive Oxygen Species
Authors: Akhiani Ali A. , Hallner Alexander , Kiffin Roberta , Aydin Ebru , Werlenius Olle , Aurelius Johan , Martner Anna , Thorén Fredrik B. , Hellstrand Kristoffer 
Published: September 2020

AbstractThe phosphatidylinositol-4,5-bisphosphate-3 kinase-δ (PI3Kδ) inhibitor idelalisib, used alone or in combination with anti-CD20, is clinically efficacious in B-cell lymphoma and chronic lymphocytic leukemia (CLL) by promoting apoptosis of malignant B cells. PI3K regulates the formation of reactive oxygen species (ROS) by the myeloid NADPH oxidase NOX2, but the role of PI3Kδ in myeloid cell–induced immunosuppression is unexplored. We assessed the effects of idelalisib on the spontaneous and IgG antibody–induced ROS production by human monocytes, on ROS-induced cell death of human natural killer (NK) cells, and on tumor cell clearance in an NK cell–dependent mouse model of metastasis. Idelalisib potently and efficiently inhibited the formation of NOX2-derived ROS from monocytes and rescued NK cells from ROS-induced cell death. Idelalisib also promoted NK cell cytotoxicity against anti–CD20-coated primary human CLL cells and cultured malignant B cells. Experiments using multiple PI3K inhibitors implicated the PI3Kδ isoform in regulating NOX2-induced ROS formation and immunosuppression. In B6 mice, systemic treatment with idelalisib significantly reduced the formation of lung metastases from intravenously injected melanoma cells but did not affect metastasis in B6.129S6-Cybbtm1Din (Nox2−/−) mice or in NK cell–deficient mice. Our results imply that idelalisib rescues NK cells from NOX2/ROS-dependent immunosuppression and thus exerts antineoplastic efficacy beyond B-cell inhibition.
Automated Recognition of Regional Wall Motion Abnormalities Through Deep Neural Network Interpretation of Transthoracic Echocardiography
Authors: Huang Mu-Shiang , Wang Chi-Shiang , Chiang Jung-Hsien , Liu Ping-Yen , Tsai Wei-Chuan 
Published: September 2020

Background:
Automated interpretation of echocardiography by deep neural networks could support clinical reporting and improve efficiency. Whereas previous studies have evaluated spatial relationships using still frame images, we aimed to train and test a deep neural network for video analysis by combining spatial and temporal information, to automate the recognition of left ventricular regional wall motion abnormalities.

Methods:
We collected a series of transthoracic echocardiography examinations performed between July 2017 and April 2018 in 2 tertiary care hospitals. Regional wall abnormalities were defined by experienced physiologists and confirmed by trained cardiologists. First, we developed a 3-dimensional convolutional neural network model for view selection ensuring stringent image quality control. Second, a U-net model segmented images to annotate the location of each left ventricular wall. Third, a final 3-dimensional convolutional neural network model evaluated echocardiographic videos from 4 standard views, before and after segmentation, and calculated a wall motion abnormality confidence level (0–1) for each segment. To evaluate model stability, we performed 5-fold cross-validation and external validation.

Results:
In a series of 10 638 echocardiograms, our view selection model identified 6454 (61%) examinations with sufficient image quality in all standard views. In this training set, 2740 frames were annotated to develop the segmentation model, which achieved a Dice similarity coefficient of 0.756. External validation was performed in 1756 examinations from an independent hospital. A regional wall motion abnormality was observed in 8.9% and 4.9% in the training and external validation datasets, respectively. The final model recognized regional wall motion abnormalities in the cross-validation and external validation datasets with an area under the receiver operating characteristic curve of 0.912 (95% CI, 0.896–0.928) and 0.891 (95% CI, 0.834–0.948), respectively. In the external validation dataset, the sensitivity was 81.8% (95% CI, 73.8%–88.2%), and specificity was 81.6% (95% CI, 80.4%–82.8%).

Conclusions:
In echocardiographic examinations of sufficient image quality, it is feasible for deep neural networks to automate the recognition of regional wall motion abnormalities using temporal and spatial information from moving images. Further investigation is required to optimize model performance and evaluate clinical applications.
Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human
Authors: Pan Huize , Xue Chenyi , Auerbach Benjamin J. , Fan Jiaxin , Bashore Alexander C. , Cui Jian , Yang Dina Y. , Trignano Sarah B. , Liu Wen , Shi Jianting , Ihuegbu Chinyere O. , Bush Erin C. , Worley Jeremy , Vlahos Lukas , Laise Pasquale , Solomon Robert A. , Connolly Edward S. , Califano Andrea , Sims Peter A. , Zhang Hanrui , Li Mingyao , Reilly Muredach P. 
Published: September 2020

Background:
Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive.

Methods:
To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro.

Results:
We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed “SEM” cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability.

Conclusions:
Integration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.