bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconsidering sickle cell trait testing of red blood cell units allocated to children with sickle cell disease
Authors: Hajjaj Omar I. , Cserti‐Gazdewich Christine , Dumevska Letka , Hanna Mirette , Lau Wendy , Lieberman Lani ,   the Canadian Obstetrical Pediatric Transfusion Network
Published: December 2022

AbstractBackgroundSickle cell trait (SCT) testing of red blood cell (RBC) units is sometimes performed to identify and divert units containing hemoglobin S (HbS). Recipients strategically guarded against this exposure include fetuses, neonates, and children with sickle cell disease (SCD). The clinical necessity of this practice is unclear.Study Design and MethodsA one‐year audit (2018) was performed at a pediatric tertiary care hospital that tests for SCT in RBC units prescribed to children with SCD and neonates. The impact of incorporating varying numbers of SCT RBC units in a single‐unit top‐up, partial‐manual red cell exchange, and automated erythrocytapheresis was modeled in four typical‐parameter age scenarios (2, 5, 10, and 18 years) sharing a high baseline HbS. Additionally, a survey assessing SCT testing practices was administered to Canadian pediatric hospital transfusion laboratories serving hemoglobinopathy programs.ResultsOf 2268 donor RBC units tested, one was positive for SCT (0.04% [95% CI: 0.01%–0.24%]), at a cost of $19,384.56 CAD. The impact of SCT unit incorporation on lost HbS reduction was modest (Δ1%–3% [automated erythrocytapheresis] and Δ4%–15% [top‐up/partial manual exchange]). The survey (with all 13 sites responding) showed variable SCT testing practice; four (31%) do not test, four (31%) test for children with SCD, and six (46%) test for neonates.ConclusionRBC SCT testing may be more costly than beneficial or necessary in children with SCD. As of 2019, our transfusion service has ceased SCT testing for this population. Further research in the fetal/neonatal populations is needed to overturn this entrenched practice.
Ocular surface physiology and aqueous tear secretion in cats of diverse cephalic conformations
Authors: Oksa‐Minaļto Jelena , Maggs David J. , Akimova Jekaterina , Ilgaža Aija , Sebbag Lionel 
Published: December 2022

AbstractObjectiveTo describe normative ocular surface and aqueous tear testing data for cats of various cephalic conformation.Animals studiedFifty‐three healthy adult cats (11 British Shorthair, 11 Burmese, 10 Devon Rex, 10 Scottish Fold, and 11 Sphynx).ProceduresBlink rate, corneal tactile sensation (CTS), and Schirmer tear test with or without topical anesthesia (STT‐1, STT‐2) and with nasolacrimal stimulation (NL‐STT1, NL‐STT2) were assessed. Palpebral fissure length (PFL) and skull morphology were measured, and cephalic index (CI) and craniofacial ratio (CFR) calculated.ResultsMean ± SD test results were as follows: blink rate (5.0 ± 2.3 blinks/min), CTS (3.2 ± 0.7 cm), STT‐1 (11.2 ± 4.3 mm/min), STT‐2 (6.7 ± 3.6 mm/min), NL‐STT1 (13.4 ± 5.7 mm/min), NL‐STT2 (13.5 ± 5.2 mm/min), and PFL (2.0 ± 0.2 cm). Corneal sensitivity did not differ significantly among breeds (p = .152) but was negatively correlated with body weight (r = −.32, p = .019). STT‐1 significantly differed among breeds (p < .001) and was lowest in Sphynx cats (8.7 ± 4.3 mm/min). A positive correlation was detected between STT‐1 values at 30 and 60 s (r = .98; p < .001). The nasolacrimal reflex significantly increased STT in anesthetized and unanesthetized eyes (approximately +100% and +20%, respectively; p ≤ .002). STT‐1 tended to be higher in intact versus neutered cats (p = .062). Age did not impact any test result (p ≥ .085).ConclusionsNormative data described here serve as a baseline for future studies assessing ocular surface disease in multiple feline breeds. Unlike dogs, brachycephalic cats did not have lower CTS or STT‐1 than non‐brachycephalic cats.
Human performance augmentation: the importance of integrative physiological quantification
Authors: Ryan Benjamin J. , Charkoudian Nisha , Joyner Michael J. 
Published: December 2022

AbstractIn recent years, there has been an explosion of new approaches (technological, methodological, pharmacological, etc.) designed to improve physical performance for athletes, the military and in other applications. The goal of the present discussion is to review and quantify several ways in which physiology can provide important insights about which tools may lead to improved performance (and may therefore be worth resource investment) and which tools are less likely to provide meaningful enhancement. To address these objectives, we review examples of technological solutions/approaches in terms of the magnitude of their potential (or actual) influences: transformational, moderate, ineffective or undetermined. As one example, if there were a technology which significantly increased arterial oxygen partial pressure by 10%, this would be relatively meaningless in healthy people resting at sea level, where it would have a minimal effect on arterial oxygen content. However, there might be specific situations where such an effect would be very helpful, including at high altitude or in some patient populations. We discuss the importance of quantitative evaluation of putative approaches to performance enhancement and highlight the important role of integrative physiologists in the development and critical appraisal of these approaches.
image
Toward stronger coupling between technical infrastructures and institutional processes in data-intensive science
Authors: Mayernik* Matthew S. 
Published: December 2022

ABSTRACT
The techniques and approaches within geoinformatics and data science rely on the effective coupling of supporting infrastructures and institutions. Without underlying infrastructures for data discovery, analysis, management, distribution, and preservation, new computational techniques wither on the vine for lack of input or remain isolated as niche tools that miss broader potential audiences. Likewise, without supporting institutions that enable governance of policies and finances, coordination of stakeholders, and validation of new knowledge and tools, technological advances become detached from the people and organizations that operate and use them. This paper centers on a case study of work within the National Center for Atmospheric Research (NCAR) and University Corporation for Atmospheric Research (UCAR) to develop effective systems and processes for research data curation, access, discovery, and preservation. By emphasizing iterative alignment of institutional work (policies, intermediaries, governance processes, routines, and financial instruments) and infrastructural work (data storage systems, repositories, tools, and interfaces), balanced progress has been made toward developing solutions to gaps in organizational data services.
Parent-reported factors associated with the emergency department presentation of children and adolescents with autism spectrum disorder and/or intellectual disability with behaviours of concern: a qualitative study
Authors: Pillai Jasmine , Dunn Karen , Efron Daryl 
Published: December 2022

ObjectiveWe aimed to examine the parent-reported factors contributing to the emergency department (ED) presentation of children and adolescents with autism spectrum disorder (autism) and/or intellectual disability (ID) with behaviours of concern (BOC).DesignQualitative study using semistructured interviews. Data were analysed phenomenologically using inductive thematic analysis.SettingThe ED of the Royal Children’s Hospital, Melbourne, Australia, a tertiary paediatric hospital.Participants14 parents and/or carers of children and adolescents with autism and/or ID who presented to ED for management of BOC.ResultsThree themes emerged from the data: (1) Parents and carers had difficulties navigating the healthcare system and accessing appropriate community supports prior to their child’s ED presentation; (2) Families presented to ED due to an inability to manage risk and/or contain their child’s behaviour, compounded by carer burn-out; (3) Presentation to ED was considered a last resort option for many families. The ED was generally unable to assist families in the ongoing management of their child’s BOC, leading to a potential need to re-present in future.ConclusionsThis study highlights the need for families of children with autism and ID and associated BOC to have improved access to appropriately skilled community health professionals, allowing their BOC to be addressed as they emerge rather than at crisis point. The findings additionally highlight the need for changes to the delivery of acute care in the management of BOC, to minimise patient distress and maximise safe and satisfactory patient outcomes.
Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease
Authors: Simon Tracey G , Roelstraete Bjorn , Alkhouri Naim , Hagström Hannes , Sundström Johan , Ludvigsson Jonas F 
Published: December 2022

ObjectiveLongitudinal evidence is lacking regarding the long-term risk of major adverse cardiovascular events (MACE) in children and young adults with non-alcoholic fatty liver disease (NAFLD).DesignThis nationwide cohort study included all Swedish children and young adults ≤25 years old with histologically confirmed NAFLD and without underlying cardiovascular disease (CVD) at baseline (1966–2016; n=699). NAFLD was defined from prospectively recorded histopathology, and further categorised as simple steatosis or non-alcoholic steatohepatitis (NASH). NAFLD patients were matched to ≤5 population controls without NAFLD or CVD (n=3353). Using Cox proportional hazards modelling, we calculated multivariable-adjusted HRs (aHRs) and 95% CIs for incident MACE (ie, ischaemic heart disease, stroke, congestive heart failure or cardiovascular mortality). In secondary analyses, we also explored rates of incident cardiac arrhythmias.ResultsOver a median follow-up of 16.6 years, incident MACE was confirmed in 33 NAFLD patients and 52 controls. NAFLD patients had significantly higher rates of MACE than controls (3.1 vs 0.9/1000 person-years (PY); difference=2.1/1000 PY; aHR=2.33, 95% CI=1.43 to 3.78), including higher rates of ischaemic heart disease (difference=1.4/1000 PY; aHR=3.07, 95% CI 1.62 to 5.83) and congestive heart failure (difference=0.5/1000 PY; aHR=3.89, 95% CI=1.20 to 12.64). Rates of incident MACE outcomes appeared to be further augmented with NASH (aHR=5.27, 95% CI=1.96 to 14.19). In secondary analyses, NAFLD patients also had significantly higher rates of cardiac arrythmias (aHR=3.16, 95% CI=1.49 to 6.68).ConclusionCompared with matched population controls, children and young adults with biopsy-proven NAFLD had significantly higher rates of incident MACE, including ischaemic heart disease and congestive heart failure. Research to better characterise cardiovascular risk in children and young adults with NAFLD should be prioritised.
Efficacy of implantable haemodynamic monitoring in heart failure across ranges of ejection fraction: a systematic review and meta-analysis
Authors: Curtain James P , Lee Matthew M Y , McMurray John JV , Gardner Roy S , Petrie Mark C , Jhund Pardeep S 
Published: December 2022

AimsWe conducted a meta-analysis of randomised controlled trials (RCTs) of implantable haemodynamic monitoring (IHM)-guided care.MethodsPubMed and Ovid MEDLINE were searched for RCTs of IHM in patients with heart failure (HF). Outcomes were examined in total (first and recurrent) event analyses.ResultsFive trials comparing IHM-guided care with standard care alone were identified and included 2710 patients across ejection fraction (EF) ranges. Data were available for 628 patients (23.2%) with heart failure with preserved ejection fraction (HFpEF) (EF ≥50%) and 2023 patients (74.6%) with heart failure with a reduced ejection fraction (HFrEF) (EF <50%). Chronicle, CardioMEMS and HeartPOD IHMs were used. In all patients, regardless of EF, IHM-guided care reduced total HF hospitalisations (HR 0.74, 95% CI 0.66 to 0.82) and total worsening HF events (HR 0.74, 95% CI 0.66 to 0.84). In patients with HFrEF, IHM-guided care reduced total worsening HF events (HR 0.75, 95% CI 0.66 to 0.86). The effect of IHM-guided care on total worsening HF events in patients with HFpEF was uncertain (fixed-effect model: HR 0.72, 95% CI 0.59 to 0.88; random-effects model: HR 0.60, 95% CI 0.32 to 1.14). IHM-guided care did not reduce mortality (HR 0.92, 95% CI 0.71 to 1.20). IHM-guided care reduced all-cause mortality and total worsening HF events (HR 0.80, 95% CI 0.72 to 0.88).ConclusionsIn patients with HF across all EFs, IHM-guided care reduced total HF hospitalisations and worsening HF events. This benefit was consistent in patients with HFrEF but not consistent in HFpEF. Further trials with pre-specified analyses of patients with an EF of ≥50% are required.PROSPERO registration numberCRD42021253905.
Characterisation of T cell receptor repertoires in coeliac disease
Authors: Lee Lik Wee , Shafiani Shahin , Crossley Beryl , Emerson Ryan O , Williamson David , Bunin Anna , Vargas Justin , Han Arnold S , Kaplan Ian M , Green Peter H R , Kirsch Ilan , Bhagat Govind 
Published: December 2022

AimsCharacterise T-cell receptor gene (TR) repertoires of small intestinal T cells of patients with newly diagnosed (active) coeliac disease (ACD), refractory CD type I (RCD I) and patients with CD on a gluten-free diet (GFD).MethodsNext-generation sequencing of complementarity-determining region 3 (CDR3) of rearranged T cell receptor β (TRB) and γ (TRG) genes was performed using DNA extracted from intraepithelial cell (IEC) and lamina propria cell (LPC) fractions and a small subset of peripheral blood mononuclear cell (PBMC) samples obtained from CD and non-CD (control) patients. Several parameters were assessed, including relative abundance and enrichment.ResultsTRB and TRG repertoires of CD IEC and LPC samples demonstrated lower clonality but higher frequency of rearranged TRs compared with controls. No CD-related differences were detected in the limited number of PBMC samples. Previously published LP gliadin-specific TRB sequences were more frequently detected in LPC samples from patients with CD compared with non-CD controls. TRG repertoires of IECs from both ACD and GFD patients demonstrated increased abundance of certain CDR3 amino acid (AA) motifs compared with controls, which were encoded by multiple nucleotide variants, including one motif that was enriched in duodenal IECs versus the PBMCs of CD patients.ConclusionsSmall intestinal TRB and TRG repertoires of patients with CD are more diverse than individuals without CD, likely due to mucosal recruitment and accumulation of T cells because of protracted inflammation. Enrichment of the unique TRG CDR3 AA sequence in the mucosa of patients with CD may suggest disease-associated changes in the TCRγδ IE lymphocyte (IEL) landscape.
Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy
Authors: Peng Peng , Lou Yue , Wang Shicheng , Wang Junjun , Zhang Zelu , Du Peishan , Zheng Jiamin , Liu Ping , Xu Lisa X 
Published: December 2022

BackgroundMyeloid‐derived suppressor cells (MDSCs) can potently inhibit T-cell activity, promote growth and metastasis of tumor and contribute to resistance to immunotherapy. Targeting MDSCs to alleviate their protumor functions and immunosuppressive activities is intimately associated with cancer immunotherapy. Natural killer (NK) cells can engage in crosstalk with multiple myeloid cells to alter adaptive immune responses, triggering T-cell immunity. However, whether the NK-cell-MDSC interaction can modulate the T-cell immune response requires further study. Cryo-thermal therapy could induce the maturation of MDSCs by creating an acute inflammatory environment to elicit a CD4+Th1-dominant immune response, but the mechanism regulating this process remains unclear.MethodsNK cells were depleted and NKG2D was blocked with monoclonal antibodies in vivo. MDSCs, NK cells and T cells were assessed by flow cytometry and isolated by magnetic-activated cell sorting (MACS). MDSCs and NK cells were cocultured with T cells to determine their immunological function. The transcriptional profiles of MDSCs were measured by qRT-PCR and RNA-sequencing. Isolated NK cells and MDSCs by MACS were cocultured to study the viability and maturation of MDSCs regulated by NK cells. TIMER was used to comprehensively examine the immunological, clinical, and genomic features of tumors.ResultsNK-cell activation after cryo-thermal therapy decreased MDSC accumulation and reprogrammed immunosuppressive MDSCs toward a mature phenotype to promote T cell antitumor immunity. Furthermore, we discovered that NK cells could kill MDSCs via the NKG2D-NKG2DL axis and promote MDSC maturation by interferon gamma (IFN-γ) in response to NKG2D. In addition, CD4+Th1-dominant antitumor immune response was dependent on NKG2D, which promoted the major histocompatibility complex Ⅱ pathway of MDSCs. High activated NK-cell infiltration and NKG2D level in tumors were positively correlated with better clinical outcomes.ConclusionsCryo-thermal therapy induces effective CD4+Th1-dominant antitumor immunity by activating NK cells to reprogram MDSCs, providing a promising therapeutic strategy for cancer immunotherapy.
A Size-Dependent Generalized Thermoelasticity Theory for Thermoelastic Damping in Vibrations of Nanobeam Resonators
Authors: Jalil Abduladheem Turki , Saleh Zuhra Muter , Imran Ahmed Falah , Yasin Yaser , Ruhaima Ali Abdul Kadhim , Gatea M. Abdulfadhil , Esmaeili Shahab 
Published: December 2022

Thermoelastic damping (TED) has been discerned as a definite source of intrinsic energy loss in miniaturized mechanical elements. The size-dependent structural and thermal behavior of these small-sized structures has been proven through experimental observations. As a first attempt, this article exploits nonlocal strain gradient theory (NSGT) and nonlocal dual-phase-lag (NDPL) heat conduction model simultaneously to acquire a mathematical formulation and analytical solution for TED in nanobeams that can accommodate size effect into both structural and heat transfer fields. For this purpose, the coupled equations of motion and heat conduction are firstly extracted via NSGT and NDPL model. Next, by deriving the distribution of temperature from heat conduction equation and substituting it in the motion equation, the unconventional thermoelastic frequency equation is established. By deriving the real and imaginary parts of the frequency from this equation and employing the definition of quality factor, an explicit solution is given for approximating TED value. The veracity of the proposed model is checked by comparing it with the solutions reported in the literature for specific and simpler cases. A diverse set of numerical results is then presented to appraise the influence of some factors like structural and thermal nonlocal parameters, strain gradient length scale parameter, geometrical parameters, mode number and material on the amount of TED. According to the results, use of NDPL model yields a smaller value for TED than DPL model, but prediction of NSGT about the magnitude of TED, in addition to the relative amounts of its two scale parameters, strongly depend on other factors such as aspect ratio, vibration mode and material type.
Divergent Roles of Ephrin-B2/EphB4 Guidance System in Pulmonary Hypertension
Authors: Crnkovic Slaven , Rittchen Sonja , Jandl Katharina , Gindlhuber Juergen , Zabini Diana , Mutgan Ayse Ceren , Valzano Francesco , Boehm Panja M. , Hoetzenecker Konrad , Toller Wolfgang , Veith Christine , Heinemann Akos , Schermuly Ralph T. , Olschewski Andrea , Marsh Leigh M. , Kwapiszewska Grazyna 
Published: December 2022

Background:
Smooth muscle cell (SMC) expansion is one key morphological hallmark of pathologically altered vasculature and a characteristic feature of pulmonary vascular remodeling in pulmonary hypertension. Normal embryonal vessel maturation requires successful coverage of endothelial tubes with SMC, which is dependent on ephrin-B2 and EphB4 ligand-receptor guidance system. In this study, we investigated the potential role of ephrin-B2 and EphB4 on neomuscularization in adult pulmonary vascular disease.

Methods and Results:
Ephrin-B2 and EphB4 expression is preserved in smooth muscle and endothelial cells of remodeled pulmonary arteries. Chronic hypoxia-induced pulmonary hypertension was not ameliorated in mice with SMC-specific conditional ephrin-B2 knockout. In mice with global inducible ephrin-B2 knockout, pulmonary vascular remodeling and right ventricular hypertrophy upon chronic hypoxia exposure were significantly diminished compared to hypoxic controls, while right ventricular systolic pressure was unaffected. In contrast, EphB4 receptor kinase activity inhibition reduced right ventricular systolic pressure in hypoxia-induced pulmonary hypertension without affecting pulmonary vascular remodeling. Genetic deletion of ephrin-B2 in murine pulmonary artery SMC, and pharmacological inhibition of EphB4 in human pulmonary artery smooth muscle cells, blunted mitogen-induced cell proliferation. Loss of EphB4 signaling additionally reduced RhoA expression and weakened the interaction between human pulmonary artery smooth muscle cells and endothelial cells in a three-dimensional coculture model.

Conclusions:
In sum, pulmonary vascular remodeling was dependent on ephrin-B2-induced Eph receptor (erythropoietin-producing hepatocellular carcinoma receptor) forward signaling in SMC, while EphB4 receptor activity was necessary for RhoA expression in SMC, interaction with endothelial cells and vasoconstrictive components of pulmonary hypertension.
Theoretical Foundation of the Linear Relationship between the Midlatitude Eddy Heat Flux and Fall-to-Spring Polar Ozone Buildup
Authors: Hasebe Fumio , Kodera Sayaka , Akiyoshi Hideharu 
Published: December 2022

Abstract
It has been demonstrated that there is a globally unified linear relationship between the interannual variations of the fall-to-spring polar ozone accumulation and the winter-mean poleward eddy heat flux on the 100 hPa pressure surface. The foundation of this relationship is investigated using time-slice experiments on a chemistry–climate model with two levels of ozone-depleting substances (ODSs). The features of the transport field are interpreted by decomposing the horizontal ozone flux caused by the residual circulation into contributing processes including the eddy heat flux with the aid of the transformed Eulerian-mean momentum equation followed by rearrangement of terms. The linear relationship between the interannual variations of the fall-to-spring ozone buildup integrated poleward and above a reference point Pref on a meridional plane and the poleward eddy heat flux during the corresponding period at Pref is realized for each hemisphere implying that the interhemispheric unification should be treated with caution. This relationship is interpreted using the fact that the interannual variation of poleward ozone transport in the upper stratosphere is captured well by the vertical convergence of the constituent-based Eliassen–Palm (EP) flux (), which is defined as the product of the constituent (ozone) mixing ratio and EP flux. The eddy momentum flux contributes to the meridional ozone transport in combination with the eddy heat flux in the form of the divergence of , although it is not responsible for realizing the linear relationship. The dependence of the linearity on the location of Pref and ODS levels is discussed.