bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience of point-of-care HbA1c testing in the English National Health Service Diabetes Prevention Programme: an observational study
Authors: Barron Emma , Misra Shivani , English Emma , John W Garry , Sampson Michael , Bachmann Max O , Barth Julian , Oliver Nick , Alberti K G M M , Bakhai Chirag , O'Neill Simon , Young Bob , Wareham Nicholas J , Khunti Kamlesh , Jebb Susan , Smith Jenifer , Valabhji Jonathan 
Published: March 2023

IntroductionTo report the observations of point-of-care (POC) glycated hemoglobin (HbA1c) testing in people with non-diabetic hyperglycemia (NDH; HbA1c 42–47 mmol/mol (6.0%–6.4%)), applied in community settings, within the English National Health Service Diabetes Prevention Programme (NHS DPP).Research design and methodsA service evaluation assessing prospectively collected national service-level data from the NHS DPP, using data from the first referral received in June 2016–October 2018. Individuals were referred to the NHS DPP with a laboratory-measured HbA1c in the NDH range and had a repeat HbA1c measured at first attendance of the program using one of three POC devices: DCA Vantage, Afinion or A1C Now+. Differences between the referral and POC HbA1c and the SD of the POC HbA1c were calculated. The factors associated with the difference in HbA1c and the association between POC HbA1c result and subsequent attendance of the NHS DPP were also evaluated.ResultsData from 73 703 participants demonstrated a significant mean difference between the referral and POC HbA1c of −2.48 mmol/mol (−0.23%) (t=157, p<0.001) with significant differences in the mean difference between devices (F(2, 73 700)=738, p<0.001). The SD of POC HbA1c was 4.46 mmol/mol (0.41%) with significant differences in SDs between devices (F(2, 73 700)=1542, p<0.001). Participants who were older, from more deprived areas and from Asian, black and mixed ethnic groups were associated with smaller HbA1c differences. Normoglycemic POC HbA1c versus NDH POC HbA1c values were associated with lower subsequent attendance at behavioral interventions (58% vs 67%, p<0.001).ConclusionPOC HbA1c testing in community settings was associated with significantly lower HbA1c values when compared with laboratory-measured referrals. Acknowledging effects of regression to the mean, we found that these differences were also associated with POC method, location, individual patient factors and time between measurements. Compared with POC HbA1c values in the NDH range, normoglycemic POC HbA1c values were associated with lower subsequent intervention attendance.
Acute and chronic neuroinflammation is triggered by diabetic ketoacidosis in a rat model
Authors: Glaser Nicole , Chu Steven , Hung Benjamin , Fernandez Luis , Wulff Heike , Tancredi Daniel , ODonnell Martha E 
Published: March 2023

IntroductionCognitive decline is common in patients with type 1 diabetes and has been attributed to the effects of chronic hyperglycemia and severe hypoglycemia. Diabetic ketoacidosis (DKA) has only recently been suspected to be involved in causing cognitive decline. We hypothesized that DKA triggers both acute and chronic neuroinflammation, contributing to brain injury.Research methods and designWe measured concentrations of cytokines, chemokines and matrix metalloproteinases (MMP) in serum and brain tissue lysates in juvenile rats during and after DKA (during acute DKA, 24 hours and 7 days after DKA), and compared these to healthy controls and hyperglycemic controls. We also measured cytokine, chemokine and MMP concentrations in serum and brain tissue of adult rats (70 days) that had experienced DKA as juveniles and compared these measurements to those of adult diabetic rats without exposure to DKA.ResultsDuring acute DKA in the juvenile rats, serum concentrations of CCL3, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and MMP-9 were significantly increased. Serum concentrations of IL-2 and IL-17A increased 7 days after DKA recovery. In brain tissue lysates, concentrations of CCL3, CCL5, interferon (IFN)-γ and MMP-9 were significantly elevated during acute DKA. In adult rats that had DKA as juveniles (28 days previously), serum concentrations of IL-1ß and brain concentrations of IL-10 and IL-12p70 were elevated in comparison to diabetic rats without prior DKA. Composite scores for highly correlated cytokines and chemokines (mean z-scores for IL-10, IL-1ß, TNF-α, IL-17A, IFN-γ, CXCL-1 and CCL5) were also significantly elevated in adult rats with prior DKA.ConclusionsThese data confirm that DKA causes acute systemic inflammation and neuroinflammation in a rat model. Importantly, the neuroinflammatory response triggered by DKA is long-lasting, suggesting the possibility that DKA-induced chronic neuroinflammation could contribute to long-term cognitive decline in individuals with diabetes.
Common mental health and emotional and behavioural disorders among adolescents and young adults in Harare and Mashonaland East, Zimbabwe: a population-based prevalence study
Authors: Doyle Aoife Margaret , Bandason T , Dauya E , McHugh Grace , Grundy Chris , Simms Victoria , Chibanda D , Ferrand Rashida 
Published: March 2023

ObjectivesTo estimate the prevalence of common mental health disorders (CMDs) and emotional and behavioural disorders among young people and to explore the correlates of CMDs risk.SettingFive urban and periurban communities in Harare and Mashonaland East, ZimbabweDesignPopulation-based cross-sectional studyParticipantsYoung people aged 13–24 years living in households in the study areas.Outcome measuresThe primary outcome was the proportion of participants screening positive for probable CMDs defined as a Shona Symptoms Questionnaire (SSQ) score ≥8. Secondary outcomes were emotional and behavioural disorders measured using the Strength and Difficulties Questionnaire (SDQ), and adjusted ORs for factors associated with CMD.ResultsOut of 634 young people, 37.4% (95% CI 33.0% to 42.0%) screened positive for probable CMDs, 9.8% (95% CI 7.5% to 12.7%) reported perceptual symptoms and 11.2% (95% CI 9.0% to 13.8%) reported suicidal ideation. Using UK norms to define normal, borderline and abnormal scores for each of the SDQ domains, a high proportion (15.8%) of Zimbabwean young people had abnormal scores for emotional symptoms and a low proportion had abnormal scores for hyperactivity/inattention scores (2.8%) and prosocial scores (7.1%). We created local cut-offs for the emotional symptoms, hyperactivity/attention and prosocial SDQ domains. The odds of probable CMDs increased with each year of age (OR 1.09, p<0.001) and was higher among those who were out of school and not working compared with those in school or working (adj. OR 1.67 (1.07, 2.62), p=0.04). One in five participants (22.1%) were referred immediately for further clinical assessment but uptake of referral services was low.ConclusionsWe observed a high prevalence of symptoms of CMDs among general population urban and peri-urban young people especially among those with no employment. There is a need for more accessible and acceptable youth-friendly mental health services.
Partner alcohol consumption and intimate partner violence among women in Papua New Guinea: a cross-sectional analysis of Demographic and Health Survey
Authors: Cadri Abdul , Aboagye Richard Gyan , Boadu Frimpong James , Yeboah Paa Akonor , Seidu Abdul-Aziz , Ahinkorah Bright Opoku 
Published: March 2023

ObjectiveWe examined the association between partner alcohol consumption and the experience of intimate partner violence among women in Papua New Guinea.DesignWe performed a cross-sectional analyses of data extracted from the 2016–2018 Papua New Guinea Demographic and Health Survey. We included 3319 women in sexual unions. Multilevel binary logistic regression analysis was used to examine the association between partner alcohol consumption and intimate partner violence, controlling for the covariates. Results from the regression analysis were presented using the crude odds ratios (cORs) and adjusted odds ratios (aORs), with 95% confidence intervals (CIs).SettingPapua New Guinea.ParticipantsWomen aged 15–49 years in sexual unions.Outcome measuresPhysical, emotional, and sexual violence.ResultsThe prevalence of physical, emotional and sexual violence among women in sexual unions in Papua New Guinea were 45.9% (42.4 to 47.7), 45.1% (43.4 to 46.8) and 24.3% (22.9 to 25.8), respectively. The level of partner alcohol consumption was 57.3%. Women whose partners consumed alcohol were more likely to experience physical violence (aOR=2.86, 95% CI=2.43 to 3.37), emotional violence (aOR=2.89, 95% CI=2.44 to 3.43) and sexual violence (aOR=2.56, 95% CI=2.08 to 3.16) compared with those whose partners did not consume alcohol.ConclusionThis study found a relatively high prevalence of intimate partner violence among women in Papua New Guinea. Most importantly, this study found partner alcohol consumption to be significantly and positively associated with intimate partner violence. The study, therefore, recommends that interventions seeking to reduce intimate partner violence among women in Papua New Guinea should intensify behaviour change and education on reducing or eliminating partner alcohol consumption.
Strategies, challenges and opportunities in the implementation of COVID-19 field hospitals: a scoping review
Authors: Hamis Amy Azira , Md Bukhori Ayuzeity Bistari , Heng Pei Pei , Jane Ling Miaw Yn , Shaharuddin Muhammad Al-Amin , A Fauzi Nazmeen Adline Fawwazah , Masdor Noor Azreen , Othman Rahayu , Ismail Aniza 
Published: March 2023

ObjectivesCOVID-19 has strained healthcare systems, requiring the redesign of their structure, human resource management and clinical approach. Countries have adopted implementation strategies and maximise field hospital functionality to address the issue of overflow of patients with COVID-19. This scoping review was based on the main research question, ‘What are the implementation strategies, challenges and opportunities in managing the field hospital during the COVID-19 pandemic?’, and aimed to consolidate all recent evidence on COVID-19 field hospital implementation approaches, challenges and potentialities.DesignScoping review, following the Arksey and O’Malley’s framework, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.Data sourcesPubMed, Web of Science and Scopus were searched from 1 January 2020 through 31 December 2021.Eligibility criteriaOriginal articles, reviews, case studies and reports written in English were included. Works without full article and articles that did not answer the research questions were excluded.Data extraction and synthesisData were extracted using a standardised data extraction form in Microsoft Excel. The findings of all included articles were synthesised narratively.ResultsEighty-five records were reviewed and 25 studies were included. For the field hospital implementation strategies, ‘surge capacity’, namely space, human resource, supply and system, was discussed in addition to the preparation and workflow of other services such as pharmacy, rehabilitation, food and nutrition. The management of COVID-19 field hospitals is challenging with respect to staff and resource shortages, inability to anticipate patient load and poor communication. The opportunities and recommendations for improvement of management were also highlighted.ConclusionsThe compilation of lessons learnt may help improve the future management of field hospitals, administratively and clinically.
Comprehensive molecular phenotyping ofARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities
Authors: Xu Chang , Huang Kie Kyon , Law Jia Hao , Chua Joy Shijia , Sheng Taotao , Flores Natasha M , Pizzi Melissa Pool , Okabe Atsushi , Tan Angie Lay Keng , Zhu Feng , Kumar Vikrant , Lu Xiaoyin , Benitez Ana Morales , Lian Benedict Shi Xiang , Ma Haoran , Ho Shamaine Wei Ting , Ramnarayanan Kalpana , Anene-Nzelu Chukwuemeka George , Razavi-Mohseni Milad , Abdul Ghani Siti Aishah Binte , Tay Su Ting , Ong Xuewen , Lee Ming Hui , Guo Yu Amanda , Ashktorab Hassan , Smoot Duane , Li Shang , Skanderup Anders Jacobsen , Beer Michael A , Foo Roger Sik Yin , Wong Joel Shi Hao , Sanghvi Kaushal , Yong Wei Peng , Sundar Raghav , Kaneda Atsushi , Prabhakar Shyam , Mazur Pawel Karol , Ajani Jaffer A , Yeoh Khay Guan , So Jimmy Bok-Yan , Tan Patrick 
Published: March 2023

ObjectiveGastric cancer (GC) is a leading cause of cancer mortality, withARID1Abeing the second most frequently mutated driver gene in GC. We sought to decipherARID1A-specific GC regulatory networks and examine therapeutic vulnerabilities arising fromARID1Aloss.DesignGenomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures ofARID1Ainactivation across molecular subtypes. Single-cell transcriptomic profiles ofARID1A-mutated GCs were analysed to examine tumour microenvironmental changes arising fromARID1Aloss. Genome-wide ARID1A binding and chromatin profiles (H3K27ac, H3K4me3, H3K4me1, ATAC-seq) were generated to identify gastric-specific epigenetic landscapes regulated by ARID1A. Distinct cancer hallmarks ofARID1A-mutated GCs were converged at the genomic, single-cell and epigenomic level, and targeted by pharmacological inhibition.ResultsWe observed prevalentARID1Ainactivation across GC molecular subtypes, with distinct mutational signatures and linked to a NFKB-driven proinflammatory tumour microenvironment.ARID1A-depletion caused loss of H3K27ac activation signals atARID1A-occupied distal enhancers, but unexpectedly gain of H3K27ac at ARID1A-occupied promoters in genes such asNFKB1andNFKB2. Promoter activation inARID1A-mutated GCs was associated with enhanced gene expression, increased BRD4 binding, and reduced HDAC1 and CTCF occupancy. Combined targeting of promoter activation and tumour inflammation via bromodomain and NFKB inhibitors confirmed therapeutic synergy specific toARID1A-genomic status.ConclusionOur results suggest a therapeutic strategy forARID1A-mutated GCs targeting both tumour-intrinsic (BRD4-assocatiated promoter activation) and extrinsic (NFKB immunomodulation) cancer phenotypes.
Rear-facing child safety seat effectiveness: evidence from motor vehicle crash data
Authors: Anderson D Mark , Peterson Ridge W 
Published: March 2023

IntroductionIn 2018, the American Academy of Pediatrics updated their car safety seat (CSS) guidelines to recommend that children ride rear-facing as long as possible, yet evidence from observational studies on rear-facing CSS effectiveness is limited. This study estimated the association between rear-facing CSS use and injuries among children aged 0–4 years who were involved in motor vehicle crashes (MVCs).MethodsThis study analysed data on all MVCs involving children aged 0–4 years reported to the Kansas Department of Transportation from 2011 to 2020. Children who were in a rear-facing CSS were compared with children who rode in a forward-facing device. Logistic regression was used to adjust for potential confounders.ResultsIn unadjusted models, rear-facing CSS use was associated with a 14% reduction in the odds of suffering any injury versus riding in a forward-facing CSS (OR 0.860, 95% CI 0.805 to 0.919). In models adjusted for potential confounders, rear-facing CSS use was associated with a 9% reduction in the odds of any injury relative to riding forward-facing (OR 0.909, 95% CI 0.840 to 0.983). These estimates were driven by children seated in the back outboard positions. Rear-facing CSS use was also negatively associated with incapacitating/fatal injuries, but these estimates were imprecise.ConclusionsChildren aged 0–4 years are less likely to be injured in an MVC if they are restrained in a rear—as opposed to forward—facing CSS. These results are particularly relevant because a number of state CSS laws do not require children of any age to ride rear-facing.
Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering
Authors: Michels Kathryn R , Sheih Alyssa , Hernandez Susana A , Brandes Alissa H , Parrilla Don , Irwin Blythe , Perez Anai M , Ting Hung-An , Nicolai Christopher J , Gervascio Timothy , Shin Seungjin , Pankau Mark D , Muhonen Mason , Freeman Jessica , Gould Sarah , Getto Rich , Larson Ryan P , Ryu Byoung Y , Scharenberg Andrew M , Sullivan Alessandra M , Green Shon 
Published: March 2023

BackgroundChimeric antigen receptor (CAR) T-cell therapies have demonstrated transformational outcomes in the treatment of B-cell malignancies, but their widespread use is hindered by technical and logistical challenges associated with ex vivo cell manufacturing. To overcome these challenges, we developed VivoVec, a lentiviral vector-based platform for in vivo engineering of T cells. UB-VV100, a VivoVec clinical candidate for the treatment of B-cell malignancies, displays an anti-CD3 single-chain variable fragment (scFv) on the surface and delivers a genetic payload that encodes a second-generation CD19-targeted CAR along with a rapamycin-activated cytokine receptor (RACR) system designed to overcome the need for lymphodepleting chemotherapy in supporting successful CAR T-cell expansion and persistence. In the presence of exogenous rapamycin, non-transduced immune cells are suppressed, while the RACR system in transduced cells converts rapamycin binding to an interleukin (IL)-2/IL-15 signal to promote proliferation.MethodsUB-VV100 was administered to peripheral blood mononuclear cells (PBMCs) from healthy donors and from patients with B-cell malignancy without additional stimulation. Cultures were assessed for CAR T-cell transduction and function. Biodistribution was evaluated in CD34-humanized mice and in canines. In vivo efficacy was evaluated against normal B cells in CD34-humanized mice and against systemic tumor xenografts in PBMC-humanized mice.ResultsIn vitro, administration of UB-VV100 resulted in dose-dependent and anti-CD3 scFv-dependent T-cell activation and CAR T-cell transduction. The resulting CAR T cells exhibited selective expansion in rapamycin and antigen-dependent activity against malignant B-cell targets. In humanized mouse and canine studies, UB-VV100 demonstrated a favorable biodistribution profile, with transduction events limited to the immune compartment after intranodal or intraperitoneal administration. Administration of UB-VV100 to humanized mice engrafted with B-cell tumors resulted in CAR T-cell transduction, expansion, and elimination of systemic malignancy.ConclusionsThese findings demonstrate that UB-VV100 generates functional CAR T cells in vivo, which could expand patient access to CAR T technology in both hematological and solid tumors without the need for ex vivo cell manufacturing.
Kantowski–Sachs cosmology in scalar-torsion theory
Authors: Paliathanasis Andronikos 
Published: March 2023

AbstractIn the context of scalar-torsion theory we investigate the evolution of the cosmological anisotropies for a Kantowski–Sachs background geometry. We study the phase-space of the gravitational field equations by determining the admitted stationary points and study their stability properties. For the potential function of the non-minimally coupled scalar field we assume the exponential and the power-law functions. Finally, we make use of Poincare variables in order to investigate the existence of stationary points at the infinity regime of the dynamics.
Lazy Load Scheduling for Mixed-criticality Applications in Heterogeneous MPSoCs
Authors: Kloda Tomasz , Gracioli Giovani , Tabish Rohan , Mirosanlou Reza , Mancuso Renato , Pellizzoni Rodolfo , Caccamo Marco 
Published: March 2023

Newly emerging multiprocessor system-on-a-chip (MPSoC) platforms provide hard processing cores with programmable logic (PL) for high-performance computing applications. In this article, we take a deep look into these commercially available heterogeneous platforms and show how to design mixed-criticality applications such that different processing components can be isolated to avoid contention on the shared resources such as last-level cache and main memory.

Our approach involves software/hardware co-design to achieve isolation between the different criticality domains. At the hardware level, we use a scratchpad memory (SPM) with dedicated interfaces inside the PL to avoid conflicts in the main memory. At the software level, we employ a hypervisor to support cache-coloring such that conflicts at the shared L2 cache can be avoided. In order to move the tasks in/out of the SPM memory, we rely on a DMA engine and propose a new CPU-DMA co-scheduling policy, called
Lazy Load
, for which we also derive the response time analysis. The results of a case study on image processing demonstrate that the contention on the shared memory subsystem can be avoided when running with our proposed architecture. Moreover, comprehensive schedulability evaluations show that the newly proposed
Lazy Load
policy outperforms the existing CPU-DMA scheduling approaches and is effective in mitigating the main memory interference in our proposed architecture.
Genetic variants in the endothelial protein C receptor gene: reaching significance
Authors: de Frutos Pablo García 
Published: March 2023

SummarySince the discovery of activated protein C (APC) resistance, mutations and genetic variants in the protein C pathway have been put into the spotlight of research in the pathophysiology of haemostasis. Although none of the more recently discovered mutations in the components of the natural anticoagulant pathways have equalled the clear-cut effect of factor V Leiden in thrombosis and its epidemiological importance, some recent work in several genes of the pathway have shown promising results in linking genotype and phenotype which could explain certain mechanisms in respective thrombosis associated pathologies. The discovery of a specific endothelial protein C receptor (EPCR) and the deciphering of its importance in the biology of protein C, opened up the possibility that genetic variants in the EPCR gene (PROCR) could play a role in the risk for thrombosis (1, 2). The EPCR functions to enhance the activation of anticoagulant protein C by the thrombin-thrombomodulin complex, and it is essential for the interaction of protein C with protease activated receptor 1. In this way, the EPCR acts in the anticoagulant, profibrinolytic and anti-inflammatory response (1, 3, 4). EPCR knock-out mice show early embryonic lethality (5), although a small amount of EPCR is sufficient to maintain the animals alive and fertile (6) …