bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID‐19 – a regional blood centre's perspective
Authors: Leung Jennifer N. S. , Lee Cheuk-Kwong 
Published: April 2020

COVID‐19 pandemic has caused an overwhelming pressure to everyone around the world. Not only public healthcare system is overloaded with patients, but also public are panic, restricted in their mobility, and their daily life are completely changed. As a regional blood centre in part of China, the first 3 months of year 2020 were both painful and stressful in managing both the blood safety and supply. However, the experience gained and measures implemented to overcome blood shortage and gain donors’ confidence in safe blood donation were fruitful. All these should further be incorporated into the existing contingency plan in managing emerging infectious diseases and shared among colleagues in transfusion communities.
Machine Learning Approaches for Performance Assessment of Nuclear Fuel Assemblies Subject to Seismic-Induced Impacts
Authors: Altieri Domenico , Robin-Boudaoud Marie-Cécile , Kessler Hannes , Pellissetti Manuel , Patelli Edoardo 
Published: April 2020

Abstract
In pressurized water nuclear reactors, the seismic performance of fuel assemblies is governed by their spacer grids (SGs) which may experience impacts with neighboring fuel assembly SGs or with the core barrel, depending on the intensity of the seismic event. Nonlinear dynamic analysis aiming at computing the maximum permanent deformation in a statistic framework is computationally demanding due to the different possible core configurations and the dimension of the dataset of seismic excitations. Hence, surrogate models trained by the physics-based dynamic model are proposed to analyze different scenarios, i.e., explore the space of potential core configurations and seismic excitations. Starting from ground motion records corresponding to six levels of seismic hazard, the dynamic excitation at the elevation of the reactor pressure vessel is obtained via transfer functions. Correlation between different seismic intensity measures and the maximum permanent deformation is evaluated. The performance of two well-established surrogate models, namely, artificial neural networks (ANN) and Gaussian process (GP) for regression problems is analyzed and discussed. Bayesian techniques are adopted to enhance the robustness of the trained surrogate models by training sets of neural networks and estimating the hyper-parameter of the GP.
Revisiting the Basis for Hip Fracture Prediction Through Bone Mineral Density Scans: Large Potential Errors and Improved Methods
Authors: Munsell, Jr. W. P. 
Published: April 2020

Abstract
Researchers have attempted to evaluate the likelihood of hip fracture as a function of an engineering concept called the moment of inertia, as applied to the cross-sectional area of hip bones. While the premise is sound, the results have been disappointing. Although several authors have acknowledged that errors may arise in the current methods investigators employ to determine the cross section moment of inertia (CSMI), none have looked critically at the sources, or even the magnitude, of those errors. This paper evaluates the nature of the error that can be introduced by the use of one-dimensional bone mineral density scans to estimate the CSMI and quantifies its impact on predictive calculations. In addition, this paper presents an improved method for approximating the mechanical section properties of highly complex cross sections. The factors affecting the accuracy of the proposed method are tested, and its error rate is also quantified. The method employs a two-dimensional analysis of digital images of the subject cross section and does not require extensive user expertise or investment in expensive finite element analysis programs to implement. The limited file space necessary to install the required code means that standard smart phones could be used to directly evaluate the most complex cross section in the field.
Continuous Phase Control of Vanadium Dioxide Films
Authors: Dai Jiguo , Annasiwatta Chandika , Bernussi Ayrton , Fan Zhaoyang , Berg Jordan M. , Ren Beibei 
Published: April 2020

Abstract
Vanadium dioxide (VO2) undergoes a metal-insulator transition (MIT) at approximately 68 °C, with associated sharp changes in its physical (e.g., optical, electrical, and mechanical) properties. This behavior makes VO2 films of interest in many potential applications, including memory devices, switches, sensors, and optical modulators. For ON/OFF like digital applications, an abrupt switching behavior is ideal. However, to continuously change VO2 metal/insulator phase ratio for analog-like operation, the intrinsic hysteresis characteristic of VO2 MIT renders the phase control becoming a formidable challenge. This paper considers the problem of controlling and tracking desired optical transmittance via continuous phase ratio change. The problem becomes worse while considering the differences of individual thin-film samples and the hysteresis associated with the phase change within a narrow temperature range. This paper reports a robust feedback controller using an optical transmittance measurement and based on an uncertainty and disturbance estimator (UDE) architecture. The proposed controller is capable of mitigating the adverse effect of hysteresis, while also compensating for various uncertainties. The effectiveness of the proposed methodology is demonstrated with experimental validation.
Case series of coronavirus (SARS-CoV-2) in a military recruit school: clinical, sanitary and logistical implications
Authors: Baettig Sascha J , Parini A , Cardona I , Morand G B 
Published: April 2020

IntroductionA new coronavirus, called Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2), has emerged from China in late 2019 and has now caused a worldwide pandemic. The impact of COVID-19 has not been described so far in a military setting. We therefore report a case series of infected patients in a recruit school in Switzerland and the herein associated challenges.MethodsRetrospective review of COVID-19 cases among Swiss Armed Forces recruits in the early weeks of SARS-CoV-2 pandemic in the canton of Ticino, the southernmost canton of Switzerland. Positive cases were defined with two positive PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Serological testing was performed with a commercially available kit according to manufacturers’ instructions.ResultsThe first case was likely contaminated while skiing during weekend permission. He became symptomatic 4 days later, tested positive for SARS-CoV-2 and was put into isolation. He showed complete symptom resolution after 48 hours. Quarantine was ordered for all recruits with close contact in the past 2 days, a total of 55 persons out of 140 in the company. Seven out of nine recruits in one particular quarantine room became mildly symptomatic. SARS-CoV-2 PCR was positive in one of them. Seven days after initial diagnosis, the index patient and the other one from the quarantine retested positive for SARS-CoV-2, although they had been completely asymptomatic for over 96 hours. Serological testing revealed positive for both patients. All others showed negative IgM and IgG.ConclusionsYoung healthy recruits often showed a mild course of COVID-19 with rapid symptom decline but were persistent SARS-CoV-2 carriers. This illustrates how asymptomatic patients may be responsible for covert viral transmission. An early and prolonged establishment of isolation and quarantine for patients and close contacts is essential to slow down the spread of SARS-CoV-2, especially in the confined space of a military environment.
Seizure First Aid Training For people with Epilepsy (SAFE) frequently attending emergency departments and their significant others: results of a UK multi-centre randomised controlled pilot trial
Authors: Noble Adam J , Snape Dee , Nevitt Sarah , Holmes Emily A , Morgan Myfanwy , Tudur-Smith Catrin , Hughes Dyfrig A , Buchanan Mark , McVicar Jane , MacCallum Elizabeth , Goodacre Steve , Ridsdale Leone , Marson Anthony G 
Published: April 2020

ObjectiveTo determine the feasibility and optimal design of a randomised controlled trial (RCT) of Seizure First Aid Training For Epilepsy (SAFE).DesignPilot RCT with embedded microcosting.SettingThree English hospital emergency departments (EDs).ParticipantsPatients aged ≥16 with established epilepsy reporting ≥2 ED visits in the prior 12 months and their significant others (SOs).InterventionsPatients (and their SOs) were randomly allocated (1:1) to SAFE plus treatment-as-usual (TAU) or TAU alone. SAFE is a 4-hour group course.Main outcome measuresTwo criteria evaluated a definitive RCT’s feasibility: (1) ≥20% of eligible patients needed to be consented into the pilot trial; (2) routine data on use of ED over the 12 months postrandomisation needed securing for ≥75%. Other measures included eligibility, ease of obtaining routine data, availability of self-report ED data and comparability, SAFE’s effect and intervention cost.ResultsOf ED attendees with a suspected seizure, 424 (10.6%) patients were eligible; 53 (12.5%) patients and 38 SOs consented. Fifty-one patients (and 37 SOs) were randomised. Routine data on ED use at 12 months were secured for 94.1% patients. Self-report ED data were available for 66.7% patients. Patients reported more visits compared with routine data. Most (76.9%) patients randomised to SAFE received it and no related serious adverse events occurred. ED use at 12 months was lower in the SAFE+TAU arm compared with TAU alone, but not significantly (rate ratio=0.62, 95% CI 0.33 to 1.17). A definitive trial would need ~674 patient participants and ~39 recruitment sites. Obtaining routine data was challenging, taking ~8.5 months.ConclusionsIn satisfying only one predetermined ‘stop/go’ criterion, a definitive RCT is not feasible. The low consent rate in the pilot trial raises concerns about a definitive trial’s finding’s external validity and means it would be expensive to conduct. Research is required into how to optimise recruitment from the target population.Trial registration numberISRCTN13871327
Cognitive–behavioral therapy-based intervention to treat symptoms of anxiety in pregnancy in a prenatal clinic using non-specialist providers in Pakistan: design of a randomised trial
Authors: Surkan Pamela J , Hamdani Syed Usman , Huma Zill-e , Nazir Huma , Atif Najia , Rowther Armaan A , Chaudhri Rizwana , Zafar Shamsa , Mullany Luke C , Malik Abid , Rahman Atif 
Published: April 2020

IntroductionPrenatal anxiety is a prevalent condition that is harmful for women and a strong predictor of postpartum depression. This trial assesses an intervention initiated in early pregnancy to mid pregnancy among women with clinical or subclinical symptoms of anxiety in Pakistan.Methods and analysisHappy Mother, Healthy Baby(HMHB) is a phase three, two-arm, single-blind, individual randomised clinical trial conducted in the outpatient department of Holy Family Hospital, a large public tertiary care facility affiliated with Rawalpindi Medical University (RMU). Pregnant women (enrolled at ≤22 weeks of gestation) receive six individual HMHB sessions based on cognitive–behavioral therapy (CBT) and relaxation techniques that are administered by non-specialist providers and tailored to address anxiety symptoms. Two to six booster sessions are given between the fifth consecutive weekly core session and the sixth core session that occurs in the third trimester. Apart from baseline data, data are collected in the third trimester, at birth and at 6-weeks postpartum. Primary outcomes include diagnoses of postpartum common mental disorders. Secondary outcomes include symptoms of anxiety and of depression, and birth outcomes including small-for-gestational age, low birth weight and preterm birth. An economic analysis will determine the cost effectiveness of the intervention.EthicsEthics approval was obtained from the Johns Hopkins Bloomberg School of Health Institutional Review Board (Baltimore, USA), the Human Development Research Foundation Ethics Committee (Islamabad, Pakistan), the RMU Institutional Research Forum (Rawalpindi, Pakistan) and the National Institute of Mental Health-appointed Global Mental Health Data Safety and Monitoring Board.DisseminationResults from this trial will build evidence for the efficacy of a CBT-based intervention for pregnant women delivered by non-specialised providers. Identification of an evidence-based intervention for anxiety starting in early pregnancy to mid pregnancy may be transferable for use and scale-up in other low-income and middle-income countries.Trial registration numberNCT03880032.
Validity of the Medi-StuNTS behavioural marker system: assessing the non-technical skills of medical students during immersive simulation
Authors: Phillips Emma Claire , Smith Samantha Eve , Clarke Benjamin , Hamilton Ailsa Lauren , Kerins Joanne , Hofer Johanna , Tallentire Victoria Ruth 
Published: April 2020

BackgroundThe Medical Students’ Non-Technical Skills (Medi-StuNTS) behavioural marker system (BMS) is the first BMS to be developed specifically for medical students to facilitate training in non-technical skills (NTS) within immersive simulated acute care scenarios. In order to begin implementing the tool in practice, validity evidence must be sought. We aimed to assess the validity of the Medi-StuNTS system with reference to Messick’s contemporary validity framework.MethodsTwo raters marked video-recorded performances of acute care simulation scenarios using the Medi-StuNTS system. Three groups were marked: third-year and fourth-year medical students (novices), final-year medical students (intermediates) and core medical trainees (experts). The scores were used to make assessments of relationships to the variable of clinical experience through expert–novice comparisons, inter-rater reliability, observability, exploratory factor analysis, inter-rater disagreements and differential item functioning.ResultsA significant difference was found between the three groups (p<0.005), with experts scoring significantly better than intermediates (p<0.005) and intermediates scoring significantly better than novices (p=0.001). There was a strong positive correlation between the two raters’ scores (r=0.79), and an inter-rater disagreement of more than one point in less than one-fifth of cases. Across all scenarios, 99.7% of skill categories and 84% of skill elements were observable. Factor analysis demonstrated appropriate grouping of skill elements. Inconsistencies in test performance across learner groups were shown specifically in the skill categories of situation awareness and decision making and prioritisation.ConclusionWe have demonstrated evidence for several aspects of validity of the Medi-StuNTS system when assessing medical students’ NTS during immersive simulation. We can now begin to introduce this system into simulation-based education to maximise NTS training in this group.
Immune involvement of the contralateral hemisphere in a glioblastoma mouse model
Authors: Crommentuijn Matheus H W , Schetters Sjoerd T T , Dusoswa Sophie A , Kruijssen Laura J W , Garcia-Vallejo Juan J , van Kooyk Yvette 
Published: April 2020

BackgroundGlioblastoma (GBM) is the most common and deadliest form of brain cancer in adults. Standard treatment, consisting of surgery and radiochemotherapy, only provides a modest survival benefit and is incapable of combating infiltrating GBM cells in other parts of the brain. New therapies in clinical trials, such as anti-programmed cell death 1 immunotherapy, have so far shown limited success in GBM. Moreover, it is unclear how the growth of GBM suppresses the immune system locally at the site of the brain tumor or if distant sites of tumor cell migration are also involved. Invasive GBM cells in brain tissue beyond the primary tumor limit the use of surgery, thus immunotherapy could be beneficial if activated/suppressed immune cells are present in the contralateral hemisphere.MethodsHere, we used a syngeneic orthotopic GL26 GBM mouse model and multiparameter fluorescence-activated cell sorting analysis to study the phenotype of resident and infiltrating immune cells in both the brain tumor hemisphere and contralateral hemisphere.ResultsWe show that lymphoid cells, including tumor antigen-specific CD8+tumor-infiltrating lymphocytes (TILs) are present in the tumor and are characterized by a tolerogenic phenotype based on high immune checkpoint expression. Massive infiltration of myeloid cells is observed, expressing immune checkpoint ligands, suggesting an immune-dependent coinhibitory axis limiting TIL responses. Surprisingly, these phenotypes are paralleled in the contralateral hemisphere, showing that infiltrating immune cells are also present at distant sites, expressing key immune checkpoints and immune checkpoint ligands.ConclusionWhole-brain analysis indicates active immune involvement throughout the brain, both at the site of the primary tumor and in the contralateral hemisphere. Using the right combination and timing, immune checkpoint blockade could have the potential to activate immune cells at the site of the brain tumor and at distant sites, thereby also targeting diffusely infiltrating GBM cells.
Functional and mechanistic advantage of the use of a bifunctional anti-PD-L1/IL-15 superagonist
Authors: Knudson Karin M , Hicks Kristin C , Ozawa Yohei , Schlom Jeffrey , Gameiro Sofia R 
Published: April 2020

BackgroundAnti(α)-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy fails to provide durable clinical benefit for most patients with carcinoma. Recent studies suggested that strategies to reduce immunosuppressive cells, promote systemic T-cell responses and lymphocyte trafficking to the tumor microenvironment (TME) may improve efficacy. N-809 is a first-in-class bifunctional agent comprising the interleukin (IL)-15 superagonist N-803 fused to two αPD-L1 domains. Thus, N-809 can potentially stimulate effector immune cells through IL-15 and block immunosuppressive PD-L1. Here, we examined the antitumor efficacy and immunomodulatory effects of N-809 versus N-803+αPD-L1 combination.MethodsThe ability of N-809 to block PD-L1 and induce IL-15-dependent immune effects was examined in vitro and in vivo. Antitumor efficacy of N-809 or N-803+αPD-L1 was evaluated in two murine carcinoma models and an extensive analysis of immune correlates was performed in the tumor and tumor-draining lymph node (dLN).ResultsWe demonstrate that N-809 blocks PD-L1 and induces IL-15-dependent immune effects. N-809 was well-tolerated and reduced 4T1 lung metastasis, decreased MC38 tumor burden and increased survival versus N-803+αPD-L1. Compared with N-803+αPD-L1, N-809 enhanced natural killer (NK) and CD8+T-cell activation and function in the dLN and TME, relating to increased gene expression associated with interferon and cytokine signaling, lymphoid compartment, costimulation and cytotoxicity. The higher number of TME CD8+T cells was attributed to enhanced infiltration, not in situ expansion. Increased TME NK and CD8+T-cell numbers correlated with augmented chemokine ligands and receptors. Moreover, in contrast to N-803+αPD-L1, N-809 reduced immunosuppressive regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (M-MDSC) and M2-like macrophages in the TME.ConclusionsOur results suggest that N-809 functions by a novel immune mechanism to promote antitumor efficacy. Foremost, N-809 enhances intratumoral lymphocyte numbers by increasing trafficking via altered chemokine levels in the TME and chemokine receptor expression on CD8+T cells and NK cells. In addition, N-809 reduces immunosuppressive and pro-tumorigenic immune cells in the TME, including Treg, M2-like macrophages and M-MDSC. Overall, these novel effects of N-809 promote an inflamed TME, leading to lower tumor burden and increased survival. These results provide mechanistic insight and rationale supporting the potential clinical study of N-809 in patients with carcinoma.
Age, body mass index, and weight gain do not increase sympathetic activity during pregnancy
Authors: Reyes Laura M. , Badrov Mark B. , Fu Qi , Steinback Craig D. , Davenport Margie H. 
Published: April 2020

Associations between prepregnancy body mass index, gestational weight gain, maternal age, and basal sympathetic nervous system activity (SNA) in normotensive pregnant women have not been explored. Retrospective analysis of microneurography records from 74 normotensive pregnant women during their third trimester indicated that although pregnancy is associated with rapid weight gain, this does not influence SNA. There were also no associations between maternal age and SNA, but more studies are needed to confirm this interpretation. Novelty Neither age nor excessive weight gain appears to influence sympathetic activity during normotensive pregnancy.
Myeloid-Derived Suppressor Cell Subsets Drive Glioblastoma Growth in a Sex-Specific Manner
Authors: Bayik Defne , Zhou Yadi , Park Chihyun , Hong Changjin , Vail Daniel , Silver Daniel J. , Lauko Adam , Roversi Gustavo , Watson Dionysios C. , Lo Alice , Alban Tyler J. , McGraw Mary , Sorensen Mia , Grabowski Matthew M. , Otvos Balint , Vogelbaum Michael A. , Horbinski Craig , Kristensen Bjarne Winther , Khalil Ahmad M. , Hwang Tae Hyun , Ahluwalia Manmeet S. , Cheng Feixiong , Lathia Justin D. 
Published: April 2020

Abstract

Myeloid-derived suppressor cells (MDSC) that block antitumor immunity are elevated in glioblastoma (GBM) patient blood and tumors. However, the distinct contributions of monocytic (mMDSC) versus granulocytic (gMDSC) subsets have yet to be determined. In mouse models of GBM, we observed that mMDSCs were enriched in the male tumors, whereas gMDSCs were elevated in the blood of females. Depletion of gMDSCs extended survival only in female mice. Using gene-expression signatures coupled with network medicine analysis, we demonstrated in preclinical models that mMDSCs could be targeted with antiproliferative agents in males, whereas gMDSC function could be inhibited by IL1β blockade in females. Analysis of patient data confirmed that proliferating mMDSCs were predominant in male tumors and that a high gMDSC/IL1β gene signature correlated with poor prognosis in female patients. These findings demonstrate that MDSC subsets differentially drive immune suppression in a sex-specific manner and can be leveraged for therapeutic intervention in GBM.

Significance:
Sexual dimorphism at the level of MDSC subset prevalence, localization, and gene-expression profile constitutes a therapeutic opportunity. Our results indicate that chemotherapy can be used to target mMDSCs in males, whereas IL1 pathway inhibitors can provide benefit to females via inhibition of gMDSCs.
See related commentary by Gabrilovich et al., p. 1100.
This article is highlighted in the In This Issue feature, p. 1079
Harnessing CAR T-cell Insights to Develop Treatments for Hyperinflammatory Responses in Patients with COVID-19
Authors: Agarwal Sangya , June Carl H. 
Published: April 2020

Abstract

Summary:
Cytokine release and macrophage activation contribute to immunopathology after SARS-CoV-2 infection. We discuss approaches to decrease the morbidity and mortality in patients with COVID-19 by repurposing existing drugs previously developed for cancer therapy.