bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salinity Mixing and Diahaline Exchange Flow in a Large Multi-Outlet Estuary with Islands
Authors: Li Xiangyu , Lorenz Marvin , Klingbeil Knut , Chrysagi Evridiki , Gräwe Ulf , Wu Jiaxue , Burchard Hans 
Published: June 2022

Abstract
The relationship between the salinity mixing, the diffusive salt transport, and the diahaline exchange flow is examined using salinity coordinates. The diahaline inflow and outflow volume transports are defined in this study as the integral of positive and negative values of the diahaline velocity. A numerical model of the Pearl River Estuary (PRE) shows that this diahaline exchange flow is analogous to the classical concept of estuarine exchange flow with inflow in the bottom layers and outflow at the surface. The inflow and outflow magnitudes increase with salinity, while the net transport equals the freshwater discharge Qr after sufficiently long temporal averaging. In summer, intensified salinity mixing mainly occurs in the surface layers and around the islands. The patchy distribution of intensified diahaline velocity suggests that the water exchange through an isohaline surface can be highly variable in space. In winter, the zones of intensification of salinity mixing occur mainly in deep channels. Apart from the impact of freshwater transport from rivers, the transient mixing is also controlled by an unsteadiness term due to estuarine storage of salt and water volume. In the PRE, the salinity mixing and exchange flow show substantial spring–neap variation, while the universal law of estuarine mixing m = 2SQr (with m being the sum of physical and numerical mixing per salinity class S) holds over longer averaging period (spring–neap cycle). The correlation between the patterns of surface mixing, the vorticity, and the salinity gradients indicates a substantial influence of islands on estuarine mixing in the PRE.
Radiographic outcomes of the treatment of complex femoral shaft fractures (AO/OTA 32-C) with intramedullary nailing: a retrospective analysis of different techniques
Authors: Chen Yu-Hung , Liao Hsiu-Jung , Lin Shang Ming , Chang Chih-Hung , Rwei Syang-Peng , Lan Tsung-Yu 
Published: June 2022

Objectives To assess the results of open versus closed reduction in intramedullary nailing (IMN) for complex femoral fractures (Arbeitsgemeinschaft für Osteosynthesefragen Foundation/Orthopaedic Trauma Association [AO/OTA]: 32-C) and to determine the factors involved in bone healing. Methods This retrospective study involved 47 consecutive patients with complex femoral diaphyseal fractures who underwent reduction and fixation. Results All open-reduction and 12 closed-reduction patients (52.17%) had an anatomical-to-small gap. The closed-small group had the highest bone union rate (100%), followed by the open-reduction (79.17%) and closed-large groups (72.73%); intergroup differences were significant. The closed-small group had the shortest mean union time (7.31 months), followed by the open-reduction group (7.58 months). The closed-large group had a significantly longer union time (9.75 months) than those in the closed-small and open-reduction groups. Femoral radiographic union scores in the closed-small and open-reduction groups were similar at three timepoints; scores were higher than those in the closed-large group, with a significant difference 6 and 9 months post-operatively. Conclusion IMN with closed reduction for complex femoral shaft fractures had better outcomes and fewer complications versus open reduction. For unsatisfactory closed reduction outcomes (i.e., residual gap >10 mm), minimally invasive techniques or open reduction with minimal stripping should be considered.
CZecking heart failure in patients with advanced chronic kidney disease (Czech HF-CKD): Study protocol
Authors: Malik Jan , Valerianova Anna , Pesickova Satu Sinikka , Hruskova Zdenka , Bednarova Vladimira , Michalek Pavel , Polakovic Vladimir , Tesar Vladimir 
Published: June 2022

Background: Heart failure (HF) is a frequent cause of morbidity and mortality of end-stage kidney disease (ESKD) patients on hemodialysis. It is not easy to distinguish HF from water overload. The traditional HF definition has low sensitivity and specificity in this population. Moreover, many patients on hemodialysis have exercise limitations unrelated to HF. Therefore, we postulated two new HF definitions ((1) Modified definition of the Acute Dialysis Quality Improvement working group; (2) Hemodynamic definition based on the calculation of the effective cardiac output). We hypothesize that the newer definitions will better identify patients with higher number of endpoints and with more advanced structural heart disease. Methods: Cohort, observational, longitudinal study with recording predefined endpoints. Patients ( n = 300) treated by hemodialysis in six collaborating centers will be examined centrally in a tertiary cardiovascular center every 6–12 months lifelong or till kidney transplantation by detailed expert echocardiography with the calculation of cardiac output, arteriovenous dialysis fistula flow volume calculation, bio-impedance, and basic laboratory analysis including NTproBNP. Effective cardiac output will be measured as the difference between measured total cardiac output and arteriovenous fistula flow volume and systemic vascular resistance will be also assessed non-invasively. In case of water overload during examination, dry weight adjustment will be recommended, and the patient invited for another examination within 6 weeks. A composite major endpoint will consist of (1) Cardiovascular death; (2) HF worsening/new diagnosis of; (3) Non-fatal myocardial infarction or stroke. The two newer HF definitions will be compared with the traditional one in terms of time to major endpoint analysis. Discussion: This trial will differ from others by: (1) detailed repeated hemodynamic assessment including arteriovenous access flow and (2) by careful assessment of adequate hydration to avoid confusion between HF and water overload.
Cancer Survivors, Oncology, and Primary Care Perspectives on Survivorship Care: An Integrative Review
Authors: Love Madeleine , Debay Marc , Hudley Anne Charity , Sorsby Todd , Lucero Linda , Miller Stuart , Sampath Sagus , Amini Arya , Raz Dan , Kim Jae , Pathak Ranjan , Chen Yi-Jen , Kaiser Andreas , Melstrom Kurt , Fakih Marwan , Sun Virginia 
Published: June 2022

Purpose: Evidence-based models of cancer survivorship care are lacking. Such models should take into account the perspectives of all stakeholders. The purpose of this integrative review is to examine the current state of the literature on cancer survivorship care from the cancer survivor, the oncology care team, and the primary care team perspectives. Methods: Using defined inclusion and exclusion criteria, we conducted a literature search of PubMed, PsycINFO, CINAHL, and Scopus databases to identify relevant articles on the stakeholders’ perspectives on cancer survivorship care published between 2010 and 2021. We reviewed and abstracted eligible articles to synthesize findings. Results: A total of 21 studies were included in the review. Barriers to the receipt and provision of cancer survivorship care quality included challenges with communication, cancer care delivery, and knowledge. Conclusion: Persistent stakeholder-identified barriers continue to hinder the provision of quality cancer survivorship care. Improved communication, delivery of care, knowledge/information, and resources are needed to improve the quality of survivorship care. Novel models of cancer survivorship care that address the needs of survivors, oncology teams, and PCPs are needed.
Risk Factors for COVID-19 Hospitalization in School-Age Children
Authors: O’Neill Liam , Chumbler Neale R. 
Published: June 2022

Introduction With the recent emergence of the Omicron variant, there has been a rapid and alarming increase in the number of COVID-19 cases among pediatric populations. Yet few US pediatric cohort studies have characterized the clinical features of children with severe COVID-19. The objective of this study was to identify those chronic comorbidities that increase the risk of hospitalization for pediatric populations with severe COVID-19. Methods A retrospective cohort study that utilized the Texas Inpatient Public Use Data file was conducted. The study included 1187 patients (ages 5 to 19) from 164 acute-care Texas hospitals with the primary or secondary ICD-10CM diagnosis code U07.1 (COVID-19, virus identified). The baseline comparison group included 38 838 pediatric patients who were hospitalized in 2020. Multivariable binary logistic regression, controlling for patient characteristics, sociodemographic factors, and health insurance, was used to estimate the adjusted risk of hospitalization for COVID-19. Results Obesity and type 1 diabetes increased the risk of hospitalization with COVID-19 among both children (5-12 years) and adolescents (13-19 years). Adolescents with morbid obesity were 10 times more likely to have severe COVID-19 (p < 0.001). Regardless of age, single-parent households (%) for the patient's zip code was associated with an increased risk of hospitalization with COVID-19 (AOR = 1.02, CI: 1.01-1.03, p < 0.01). Other risk factors included chronic kidney disease (p < 0.05), male gender (p < 0.001), Medicaid (p < 0.001), and charity care (p < 0.001). Conclusion Pediatric providers and public health officials should consider the need to tailor clinical management and mitigation efforts for pediatric populations with identifiable risk factors for severe COVID-19. These findings can be used to improve risk communication with families of children with underlying medical conditions and to prioritize prevention measures, including vaccinations.
The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
Authors: Leen N.A. , de Weijer A.D. , van Rooij S.J.H. , Kennis M. , Baas J.M.P. , Geuze E. 
Published: June 2022

Background Although current treatments for Post-Traumatic Stress Disorder (PTSD) in war veterans are effective, unfortunately 30–50% still do not benefit from these treatments. Trauma-focused therapies, eg exposure therapy, are primarily based on extinction processes in which the endocannabinoid system (ECS) plays a significant role. Therefore, it can be hypothesized that poor treatment response on trauma-focused therapy due to extinction deficits may be associated with a poorly functioning ECS. The present study examined whether the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) are associated with post-treatment symptom reduction. Methods Blood plasma levels of AEA and 2-AG were determined in war veterans with a PTSD diagnosis ( n = 54) and combat controls ( n = 26) before and after a 6–8 month interval. During this period veterans with PTSD received trauma-focused therapy (eg cognitive behavioral therapy with exposure or eye-movement desensitization and reprocessing). Clinical symptoms were assessed before and after therapy with the Clinician Administered PTSD Scale (CAPS), State-Trait Anxiety Inventory (STAI) and Mood and Anxiety Symptom Questionnaire (MASQ). Results Regression analysis demonstrated that pretreatment endocannabinoid levels were not predictive of PTSD symptom reduction. Additionally, baseline endocannabinoid levels did not differ between either PTSD and combat controls or between combat controls, treatment responders, and non-responders. Only cortisol levels significantly decreased over time from pre- to posttreatment ( p = .041). Endocannabinoid levels were significantly lower in individuals who reported cannabis use during their lifetime, independent of PTSD diagnosis. Furthermore, correlation analysis revealed that pretreatment 2-AG levels in PTSD were positively correlated with anxious arousal ( r  = .354, p = .015) and negatively with avoidance symptoms ( r  =  -.271, p = .048). Both posttreatment AEA and 2-AG were positively correlated with trait anxiety (AEA r  = .459, p = .003; 2-AG r  = .423, p = .006), anxious arousal (AEA r  = .351, p = .024; 2-AG r  = .311, p = .048) and general distress depression symptoms (AEA r  = .414, p = .007; 2-AG r  = .374, p = .016). Conclusion Since endocannabinoids are mainly generated ‘on demand’, future work could benefit by investigating endocannabinoid circulation under both baseline and stressful conditions. In line with previous research cannabis use was associated with lower endocannabinoid levels. The correlation analysis between pre- and posttreatment endocannabinoid levels and pre- and posttreatment clinical symptomatology were exploratory analysis and should be replicated in future research.
Predicting major bleeding during extended anticoagulation for unprovoked or weakly provoked venous thromboembolism
Authors: Wells Philip S. , Tritschler Tobias , Khan Faizan , Anderson David R. , Kahn Susan R. , Lazo-Langner Alejandro , Carrier Marc , Le Gal Grégoire , Castellucci Lana A. , Shah Vinay , Kaatz Scott , Kearon Clive , Solymoss Susan , Zide Russell , Schulman Sam , Chagnon Isabelle , Mallick Ranjeeta , Rodger Marc A. , Kovacs Michael J. 
Published: June 2022

Abstract
No clinical prediction model has been specifically developed or validated to identify patients with unprovoked venous thromboembolism (VTE) who are at high risk of major bleeding during extended anticoagulation. In a prospective multinational cohort study of patients with unprovoked VTE receiving extended anticoagulation after completing ≥3 months of initial treatment, we derived a new clinical prediction model using a multivariable Cox regression model based on 22 prespecified candidate predictors for the primary outcome of major bleeding. This model was then compared with modified versions of 5 existing clinical scores. A total of 118 major bleeding events occurred in 2516 patients (annual risk, 1.7%; 95% confidence interval [CI], 1.4-2.1). The incidences of major bleeding events per 100 person-years in high-risk and non–high-risk patients, respectively, were 3.9 (95% CI, 3.0-5.1) and 1.1 (0.8-1.4) using the newly derived creatinine, hemoglobin, age, and use of antiplatelet agent (CHAP) model; 3.3 (2.6-4.1) and 1.0 (0.7-1.3) using modified ACCP score, 5.3 (0.6-19.2) and 1.7 (1.4-2.0) using modified RIETE score, 3.1 (2.3-3.9) and 1.1 (0.9-1.5) using modified VTE-BLEED score, 5.2 (3.3-7.8) and 1.5 (1.2-1.8) using modified HAS-BLED score, and 4.8 (1.3-12.4) and 1.7 (1.4-2.0) using modified outpatient bleeding index score. Modified versions of the ACCP, VTE-BLEED, and HAS-BLED scores help identify patients with unprovoked VTE who are at high risk of major bleeding and should be considered for discontinuation of anticoagulation after 3 to 6 months of initial treatment. The CHAP model may further improve estimation of bleeding risk by using continuous predictor variables, but external validation is required before its implementation in clinical practice.
In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4
Authors: Wang Hongjie , Germond Audrey , Li Chang , Gil Sucheol , Kim Jiho , Kiem Hans-Peter , Lieber André 
Published: June 2022

Abstract
We developed a new in vivo hematopoietic stem cell (HSC) gene therapy approach that involves only IV injections and does not require myeloablation/conditioning and HSC transplantation. In this approach, HSCs are mobilized from the bone marrow into the peripheral bloodstream and transduced with IV injected helper-dependent adenovirus (HDAd) vectors. A fraction of transduced HSCs returns to the bone marrow and persists there long term. Here, we report desmoglein 2 (DSG2) as a new receptor that can be used for in vivo HSC transduction. HDAd5/3+ vectors were developed that use DSG2 as a high-affinity attachment receptor, and in vivo HSC transduction and safety after IV injection of an HDAd5/3+ vector expressing green fluorescent protein (GFP) in granulocyte colony-stimulating factor/AMD3100 (plerixafor)-mobilized rhesus macaques were studied. Unlike previously used CD46-targeting HDAd5/35++ vectors, HDAd5/3+ virions were not sequestered by rhesus erythrocytes and therefore mediated ∼10-fold higher GFP marking rates in primitive HSCs (CD34+/CD45RA–/CD90+ cells) in the bone marrow at day 7 after vector injection. To further increase the return of in vivo transduced, mobilized HSCs to the bone marrow, we transiently expressed cxcr4 in mobilized HSCs from the HDAd5/3+ vector. In vivo transduction with an HDAd5/3+GFP/cxcr4 vector at a low dose of 0.4 × 1012 viral particles/kg resulted in up to 7% of GFP-positive CD34+/CD45RA–/CD90+ cells in the bone marrow. This transduction rate is a solid basis for in vivo base or prime editing in combination with natural or drug-induced expansion of edited HSCs. Furthermore, our study provides new insights into HSC biology and trafficking after mobilization in nonhuman primates.
Inhaled seralutinib exhibits potent efficacy in models of pulmonary arterial hypertension
Authors: Galkin Anna , Sitapara Ravikumar , Clemons Bryan , Garcia Eduardo , Kennedy Michael , Guimond David , Carter Laura L. , Douthitt Ashley , Osterhout Robin , Gandjeva Aneta , Slee Deborah , Salter-Cid Luisa , Tuder Rubin M. , Zisman Lawrence S. 
Published: June 2022

BackgroundSignalling through platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor kit (c-KIT) plays a critical role in pulmonary arterial hypertension (PAH). We examined the preclinical efficacy of inhaled seralutinib, a unique small-molecule PDGFR/CSF1R/c-KIT kinase inhibitor in clinical development for PAH, in comparison to a proof-of-concept kinase inhibitor, imatinib.MethodsSeralutinib and imatinib potency and selectivity were compared. Inhaled seralutinib pharmacokinetics/pharmacodynamics were studied in healthy rats. Efficacy was evaluated in two rat models of PAH: SU5416/Hypoxia (SU5416/H) and monocrotaline pneumonectomy (MCTPN). Effects on inflammatory/cytokine signalling were examined. PDGFR, CSF1R and c-KIT immunohistochemistry in rat and human PAH lung samples and microRNA (miRNA) analysis in the SU5416/H model were performed.ResultsSeralutinib potently inhibited PDGFRα/β, CSF1R and c-KIT. Inhaled seralutinib demonstrated dose-dependent inhibition of lung PDGFR and c-KIT signalling and increased bone morphogenetic protein receptor type 2 (BMPR2). Seralutinib improved cardiopulmonary haemodynamic parameters and reduced small pulmonary artery muscularisation and right ventricle hypertrophy in both models. In the SU5416/H model, seralutinib improved cardiopulmonary haemodynamic parameters, restored lung BMPR2 protein levels and decreased N-terminal pro-brain natriuretic peptide (NT-proBNP), more than imatinib. Quantitative immunohistochemistry in human lung PAH samples demonstrated increased PDGFR, CSF1R and c-KIT. miRNA analysis revealed candidates that could mediate seralutinib effects on BMPR2.ConclusionsInhaled seralutinib was an effective treatment of severe PAH in two animal models, with improved cardiopulmonary haemodynamic parameters, a reduction in NT-proBNP, reverse remodelling of pulmonary vascular pathology and improvement in inflammatory biomarkers. Seralutinib showed greater efficacy compared to imatinib in a preclinical study.
SABA use as an indicator for asthma exacerbation risk: an observational cohort study (SABINA Canada)
Authors: Noorduyn Stephen G. , Qian Christina , Johnston Karissa M. , Soliman Mena , Talukdar Manisha , Walker Brandie L. , Hernandez Paul , Penz Erika 
Published: June 2022

BackgroundPatients with asthma use short-acting β-agonists (SABA) to relieve symptoms but SABA alone does not treat underlying inflammation. Thus, over-reliance on SABA may result in poor asthma control and negative health outcomes.ObjectiveTo describe use of SABA and characterise the relationship with severe exacerbations in the Canadian provinces of Nova Scotia (NS) and Alberta (AB).MethodsIn this longitudinal Canadian SABA In Asthma (SABINA) study, patients with an asthma diagnosis were identified between 2016 and 2020 within two provincial administrative datasets (Health Data Nova Scotia and Alberta Health Services). All patients were followed for ≥24 months, with the first 12 months used to measure baseline asthma severity. Medication use and the relationship of SABA overuse (three or more canisters per year) with severe asthma exacerbations were characterised descriptively andviaregression analysis.ResultsA total of 115 478 patients were identified (NS: n=8034; AB: n=107 444). SABA overuse was substantial across both provinces (NS: 39.4%; AB: 28.0%) and across all baseline disease severity categories. Patients in NS with SABA overuse had a mean±sdannual rate of 0.46±1.11 exacerbations, compared to 0.30±1.36 for those using fewer than three canisters of SABA. Patients in AB had mean±sdexacerbation rates of 0.31±0.86 and 0.17±0.62, respectively. The adjusted risk of severe exacerbation was associated with SABA overuse (NS: incidence ratio rate 1.36, 95% CI 1.18–1.56; AB: incidence ratio rate 1.32, 95% CI 1.27–1.38).ConclusionThis study supports recent updates to Canadian Thoracic Society and Global Initiative for Asthma guidelines for asthma care. SABA overuse is associated with increased risk of severe exacerbations and can be used to identify patients at a higher risk for severe exacerbations.
The dynamic cellular and molecular features during the development of radiation proctitis revealed by transcriptomic profiling in mice
Authors: Zeng Qingzhi , Cheng Jingyang , Wu Haiyong , Liang Wenfeng , Cui Yanmei 
Published: June 2022

Abstract
Background
Radiation proctitis (RP) is the most common complication of radiotherapy for pelvic tumor. Currently there is a lack of effective clinical treatment and its underlying mechanism is poorly understood. In this study, we aimed to dynamically reveal the mechanism of RP progression from the perspective of RNomics using a mouse model, so as to help develop reasonable therapeutic strategies for RP.

Results
Mice were delivered a single dose of 25 Gy rectal irradiation, and the rectal tissues were removed at 4 h, 1 day, 3 days, 2 weeks and 8 weeks post-irradiation (PI) for both histopathological assessment and RNA-seq analysis. According to the histopathological characteristics, we divided the development process of our RP animal model into three stages: acute (4 h, 1 day and 3 days PI), subacute (2 weeks PI) and chronic (8 weeks PI), which could recapitulate the features of different stages of human RP. Bioinformatics analysis of the RNA-seq data showed that in the acute injury period after radiation, the altered genes were mainly enriched in DNA damage response, p53 signaling pathway and metabolic changes; while in the subacute and chronic stages of tissue reconstruction, genes involved in the biological processes of vessel development, extracellular matrix organization, inflammatory and immune responses were dysregulated. We further identified the hub genes in the most significant biological process at each time point using protein-protein interaction analysis and verified the differential expression of these genes by quantitative real-time-PCR analysis.

Conclusions
Our study reveals the molecular events sequentially occurred during the course of RP development and might provide molecular basis for designing drugs targeting different stages of RP development.