bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Cell-Free DNA After Embolization
Authors: Sun Yi , Cai Ren , Wang Zhenfeng , Wang Deming , Zhao Xiong , Yue Xiaojie , Gu Hao , Shi Hao , Liu Yun , Fan Xindong , Su Lixin 
Published: February 2023

Objectives:
To identify genetic variants in venous malformations for noninvasive diagnosis using peripheral plasma Cell-free DNA (cfDNA) after ethanol embolization.

Method:
In this prospective, multicenter and cross-sectional study with a total of 121 patients with venous malformation, next-generation sequencing with a targeted panel of 40 specific genes was conducted to detect variants. We collected peripheral blood samples, cfDNA samples isolated from peripheral plasma before and 1 hour after ethanol embolization in 24 patients in a pilot study, and paired lesion plasma samples in 7 of those patients. Then variant profiles of peripheral postembolization plasma cfDNA were prospectively collected and analyzed from 97 patients in an independent validation group.

Results:
Variants were detected in cfDNA samples, but none was detected in paired peripheral blood. The prevalence of TEK/PIK3CA variant in peripheral pre-embolization, postembolization, and lesion plasma cfDNA were 12.5%, 87.5%, and 71.4% (P < .0001), respectively, which areas under the ROC curve of 0.5625 (P = .4579), 0.9375 (P < .0001), and 0.8571 (P = .0253), respectively. In a prospective independent validation group with postembolization cfDNA analysis in 97 patients, 119 variants were identified in 90.7% (88/97) of patients with areas under the ROC curve of 0.9545 (P < .0001).

Conclusion:
cfDNA from peripheral postembolization plasma bears safe, sensitive, and reliable diagnostic potential for venous malformations.
Can Referees Assess Head Contact Penalties Correctly in Canadian Youth Ice Hockey? A Video Analysis Study
Authors: Williamson Rylen A. , Kolstad Ash T. , Eliason Paul H. , Hagel Brent E. , Emery Carolyn A. 
Published: February 2023

Objective:To help address the high concussion burden in Canadian youth ice hockey, our primary objective was to examine the concurrent validity of youth ice hockey referees' ability to assess head contacts (HCs) and associated penalties using video analysis methods after implementation of the “zero tolerance for HC” policy by Hockey Canada.Study Design:Cross-sectional study.Participants:Certified Level II-III referees in Alberta, Canada.Intervention:A secured online survey with 60 videos (10 to 15 seconds) containing a player-to-player physical contact with or without a HC from elite U15 (ages 13 to 14) youth ice hockey games.Outcome Measures:Survey questions were completed by all referees for each video, including (1). ‘Did you see a player-to-player contact?’, (2). ‘Should a penalty be assessed?’, and if yes, (3). ‘Which player, penalty type, and penalty intensity?’ Referee assessments were compared with a consensus agreement from 2 national and member (top level) gold standard referees for concurrent validity through percent agreement and sensitivity/specificity measures.Results:Complete-case analysis of 100 referees (131 recruited) showed an overall median agreement of 83.5% (sensitivity = 0.74; specificity = 0.69) with the gold standard. Agreement with the gold standard was highest for HC infractions [85.1% (sensitivity = 0.80; specificity = 0.69)], followed by HC penalty type (81.5%) and penalty intensity (53.7%).Conclusions:Concurrent validity through percent agreement was high (>80%) compared with the gold standard for identifying both HC and other infractions; however, it was moderate for penalty intensity. Although knowledge of identifying HCs and penalties in this survey was acceptable, this study suggests in-game factors (eg, game management and positioning) may be a primary limitation for HC enforcement.
King-Devick Test in Wheelchair Sports: Identifying Normative Values and Effects of Exertion on Outcomes
Authors: Barfield Jean-Paul , Linens Shelley , Mickle Angela 
Published: February 2023

Objective:To establish normative baseline values on the King-Devick (KD) Test for contact wheelchair sport participants. The secondary purpose was to examine the effect of physical exertion on test score.Design:Quasiexperimental.Setting:Competitive disability sport venues before practices or games.Participants:One-hundred 43 wheelchair rugby or wheelchair basketball (WBB) players completed the study. Participants were predominantly men (87.5%) and played WBB (84%).Intervention:30-m wheelchair sprint test to fatigue.Main Outcome Measure:King-Devick Baseline Score.Results:Mean KD baseline score was 59.16 ± 15.56 seconds with significant differences (P< 0.05) identified by sport and impairment type, but not sex. Athletes with spina bifida and cerebral palsy had significantly higher mean baseline KD times than athletes with spinal cord injury. KD scores improved by 3.5% in athletes who reported “light” to “somewhat hard” exertion (RPE = 13). In a subset of athletes who performed sprints until an RPE of 18 was reached, 8 of 12 players (66.7%) demonstrated an improvement in KD score; however, large increases by a few participants caused the noticeable change.Conclusions:Normative values for wheelchair contact sport athletes are meaningfully slower than able-bodied sports participants. KD score improved with exertion with the greater improvement after moderate-intensity compared with vigorous-intensity exercise. These findings can be applied clinically to monitor athlete safety.
Does low-density lipoprotein fully explain atherosclerotic risk in familial hypercholesterolemia?
Authors: Clarke Shoa L. 
Published: February 2023

Purpose of review
Familial hypercholesterolemia (FH) is a monogenic disorder of elevated low-density lipoprotein cholesterol (LDL-C) from birth leading to increased risk for atherosclerotic cardiovascular disease. However, not all carriers of FH variants display an FH phenotype. Despite this fact, FH variants confer increased risk for atherosclerotic disease in population cohorts. An important question to consider is whether measurements of LDL-C can fully account for this risk.

Recent findings
The atherosclerotic risk associated with FH variants is independent of observed adult LDL-C levels. Modeling adult longitudinal LDL-C accounts for more of this risk compared to using a single measurement. Still, even when adjusting for observed longitudinal LDL-C in adult cohorts, FH variant carriers are at increased risk for coronary artery disease. Genetic analyses, observational studies, and clinical trials all suggest that cumulative LDL-C is a critical driver of cardiovascular risk that may not be fully appreciated by routine LDL-C measurements in adulthood. As such, FH variants confer risk independent of adult LDL-C because these variants increase cumulative LDL-C exposure starting from birth.

Summary
Both research and clinical practice focus on LDL-C measurements in adults, but measurements during adulthood do not reflect lifelong cumulative exposure to LDL-C. Genetic assessments may compliment clinical assessments by better identifying patients who have experienced greater longitudinal LDL-C exposure.
Nonalcoholic fatty liver disease: an update
Authors: Bedogni Giorgio , Palmese Francesco , Foschi Francesco Giuseppe 
Published: February 2023

Purpose of review
We discuss two recent controversial issues in the research field of fatty liver: the proposal to replace nonalcoholic fatty liver disease (NAFLD) with metabolically associated fatty liver disease (MAFLD) and the suggestion to extend to primary care the noninvasive testing for liver fibrosis that was developed for secondary care.

Recent findings
There is preliminary evidence that MAFLD-only patients are at greater risk of fibrosis than NAFLD-only patients. There are a large number of false positives associated with the downshift of noninvasive testing for liver fibrosis from secondary to primary care.

Summary
More studies are needed to compare the MAFLD and NAFLD operational definitions. Noninvasive testing of liver fibrosis also needs further evaluation before it can be used in primary care or in the general population.
THE EFFECTS OF DNASE I AND LOW-MOLECULAR-WEIGHT HEPARIN IN A MURINE MODEL OF POLYMICROBIAL ABDOMINAL SEPSIS
Authors: Medeiros Sarah K. , Sharma Neha , Dwivedi Dhruva , Cani Erblin , Zhou Ji , Dwivedi Naviya , Sohrabipour Sahar , Liaw Patricia C. 
Published: February 2023

ABSTRACT

Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. Previous studies have targeted CFDNA or histones in animal models of sepsis using DNase I or heparins, respectively, which has reduced inflammatory and thrombosis markers, thereby improving survival. In this study, we explored the possibility that the combination of DNase I and a low-molecular weight heparin (LMWH) may be a better therapeutic approach than monotherapy in a murine model of abdominal sepsis. Methods: C57Bl/6 mice (8–12 weeks old, both sexes) were subjected to either cecal ligation and puncture or sham surgery. Mice were given antibiotics, fluids, and either saline, DNase I (intraperitoneally, 20 mg/kg/8 h), LMWH (dalteparin, subcutaneously 500 IU/kg/12 h), or a combination of both (n = 12–31). Mice were monitored over 72 h for survival. Organs and blood were harvested for analysis. Levels of LMWH, CFDNA, IL-6, citrullinated histone-H3, thrombin-antithrombin complexes, and protein C were measured in plasma. Results: Administration of either DNase I (81.8%) or LMWH (83.3%, prophylactic range of 0.12 ± 0.07 IU/mL achieved) improved the survival of septic mice compared with saline- (38.7%) and combination-treated mice (48.8%, P < 0.05). Combination-treated mice also showed a small but insignificant improvement in survival compared with saline-treated cecal ligation and puncture mice. Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis.
LOW DOSE OF ESMOLOL ATTENUATES SEPSIS-INDUCED IMMUNOSUPPRESSION VIA MODULATING T-LYMPHOCYTE APOPTOSIS AND DIFFERENTIATION
Authors: Ma Ying , Cheng Zhenshun , Zheng Yong , Wang Wei , He Shaojun , Zhou Xiaolian , Yang Jiong , Wei Chaojie 
Published: February 2023

ABSTRACT

Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (TH2) and T helper 1 cells (TH1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. Methods: Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (esmolol: 5 mg·kg−1·h−1) and CLP + E-18 (esmolol: 18 mg·kg−1·h−1) groups. Eight rats were underwent sham operation. Eighteen hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and T-lymphocyte subsets counts were determined by flow cytometry, and the expression of p-Akt, Bcl-2, cleaved Caspase-3, and p-Erk1/2 in splenic CD4+ T-lymphocytes was determined by western blot and immunohistochemistry. β1-Adrenoreceptor expressions were evaluated using real-time polymerase chain reaction and immunohistochemistry. Results: Cecal ligation and puncture induced tachycardia, hypotension, hyperlactatemia, and multiple organ injury. Heart rate was unchanged in the CLP + E-5 group but decreased in the CLP + E-18 group. Hypotension, lactatemia, and multiple organ injuries were improved only in the CLP + E-5 group. T-lymphocyte apoptosis and TH2/TH1 ratio was decreased in CLP + E-5 but not in CLP + E-18. p-Akt and Bcl-2 expressions were increased, while cleaved Caspase-3 and p-Erk1/2 expressions were decreased in CLP + E-5. β1-Adrenoreceptor expressions were unchanged in both CLP + E-5 and CLP + E-18 groups. Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored TH2/TH1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease TH0 differentiation to TH2. Esmolol may be a potential immunoregulator of septic shock.
EFFECTS OF MESENCHYMAL STEM CELLS ON POSTRESUSCITATION RENAL AND INTESTINAL INJURIES IN A PORCINE CARDIAC ARREST MODEL
Authors: Chen Chuang , Ma Shuangshuang , Liao Lyuzhao , Xiao Yu , Dai Haiwen 
Published: February 2023

ABSTRACT

Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 106/kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid–binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid–binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.
Population structure and antimicrobial resistance patterns ofSalmonellaTyphi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India
Authors: Da Silva Kesia Esther , Date Kashmira , Hirani Nilma , LeBoa Christopher , Jayaprasad Niniya , Borhade Priyanka , Warren Joshua , Shimpi Rahul , Hoffman Seth Ari Sim-Son , Mikoleit Matthew , Bhatnagar Pankaj , Cao Yanjia , Dutta Shanta , Luby Stephen P , Andrews Jason R. 
Published: February 2023

ABSTRACTWe performed whole genome sequencing of 174SalmonellaTyphi and 54SalmonellaParatyphi A isolates collected through prospective and retrospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patters of emergence and spread of antimicrobial resistance. Additionally, we evaluated the relationship between the spatial distance between households and genetic clustering of isolates using hierarchical Bayesian models. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 mutations in the quinolone resistance determining region, conferring high-level resistance. Two H58 isolates carried an IncX3 resistance plasmid containingblaSHV-12, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistantS. Typhi isolates from India have evolved independently on multiple occasions. AmongS. Typhi isolates, we identified two main clades circulating in Navi Mumbai (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (OR 0.72 per km; 95% CrI: 0.66-0.79). This effect was seen for distances up to 5 km (OR 0.65 per km; 95% CrI: 0.59-0.73) but was not seen for distances beyond 5 km (OR 1.02 per km; 95% CrI: 0.83-1.26). Our findings indicate thatS. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial-genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission.
Neurocognitive Dysfunction in Children and Adolescents with Mental Illness
Authors: Nesamoney Sean , Hilton Rachel A. , Tozzi Leonardo , Williams Leanne M. 
Published: February 2023

AbstractIntroductionRobust evidence from adult samples indicates that neurocognitive dysfunction is a hallmark of many mental illnesses, contributing to the loss of daily function and quality of life that these illnesses cause. However, it is still unclear whether neurocognitive deficits associated with mental illnesses begin to manifest well before adulthood. The current study addresses this gap by evaluating neurocognitive function in four groups of children and adolescents with different mental illnesses compared to their matched healthy peers.MethodsWe evaluated the neurocognitive performance of four samples of youth diagnosed with ADHD (N=343), Anorexia (N=40), First-onset psychosis (N=25), and Conversion Disorder (N=56) with age-matched healthy controls. Performance was assessed using an objective assessment battery designed for use across diagnoses and settings and validated for its correlations with underlying brain structure and function. The resulting analyses assessed accuracy and reaction time performance for neurocognitive domains well established in the adult literature, such as cognitive flexibility, executive function, response inhibition, verbal fluency, verbal memory, visual memory, sustained attention, and working memory. Clinical and healthy group performance was compared using non-parametric testing.ResultsDistinct profiles of neurocognitive dysfunction were detected for each diagnosis. Particularly, children and adolescents with ADHD diffusely performed worse than their healthy counterparts, with exceptional impairment in working memory. Children and adolescents with anorexia displayed more specific impairments limited to response inhibition and verbal memory. While youth with ADHD had the most cognitive domains affected, youth with first-onset psychosis displayed the most severe impairments compared to healthy controls. Finally, deficits in conversion disorder were limited to cognitive flexibility, executive function, decision making, response inhibition, and working memory. These findings suggest that neurocognitive impairment in mental illness is transdiagnostic and can be detected as early as childhood or adolescence with standardized computerized testing.
Heart disease mortality in cancer survivors: A population-based study in Japan
Authors: Gon Yasufumi , Zha Ling , Sasaki Tsutomu , Morishima Toshitaka , Ohno Yuko , Mochizuki Hideki , Sobue Tomotaka , Miyashiro Isao 
Published: February 2023

AbstractBackgroundThe association between cancer survivors and heart disease mortality remains unclear. This study analyzed the risk of fatal heart disease in cancer survivors.MethodsData from the Osaka Cancer Registry collected between 1985 and 2013 and data from the vital statistics in Japan were retrospectively analyzed. Causes of death were investigated.Standardized mortality ratios (SMRs) were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Poisson regression models were used to estimate the risk of fatal heart disease in patients with cancer and other cancer subgroups.ResultsIn total, 688,473 cancer patients were included in the analysis, and 337,117 patients died during the study period. Among them, 10,781 patients died of heart disease, with 5,020 of these patients having ischemic heart disease; 3,602 patients, heart failure; 441 patients, hypertensive disease; and 1,718 patients, other heart diseases. The SMR (95% confidence interval [CI]) for heart disease was 2.85 (2.80–2.91). The SMRs (95% CIs) for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (3.17–3.35); 2.69 (2.60–2.78), and 4.47 (4.07–4.90), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. The multivariable Poisson regression model showed that males were more likely to die of heart disease than females (relative risk, 1.39; 95% CI, 1.34–1.45). Notably, the risk of fatal heart disease among cancer survivors has decreased in recent years.ConclusionsCancer survivors have a higher risk of fatal heart disease than the general population.
Towards a major methodological shift in depression research by assessing continuous scores of recurrence of illness, lifetime and current suicidal behaviors and phenome features: focus on atherogenicity and adverse childhood experiences
Authors: Maes Michael , Jirakran Ketsupar , Vasupanrajit Asara , Boonchaya-Anant Patchaya , Tunvirachaisakul Chavit 
Published: February 2023

AbstractBackgroundThe binary major depressive disorder (MDD) diagnosis is inadequate and should never be used in research.AimsThe study’s objective is to explicate our novel precision nomothetic strategy for constructing depression models based on adverse childhood experiences (ACEs), lifetime and current phenome, and biomarker (atherogenicity indices) scores.MethodsThis study assessed recurrence of illness (ROI: namely recurrence of depressive episodes and suicidal behaviors), lifetime and current suicidal behaviors and the phenome of depression, neuroticism, dysthymia, anxiety disorders, and lipid biomarkers (including ApoA, ApoB, free cholesterol and cholesteryl esters, triglycerides, high density lipoprotein cholesterol) in 67 normal controls and 66 MDD patients. We computed atherogenic and reverse cholesterol transport indices.ResultsWe were able to extract one factor from a) the lifetime phenome of depression comprising ROI, and traits such as neuroticism, dysthymia and anxiety disorders, and b) the phenome of the acute phase (based on depression, anxiety and quality of life scores). PLS analysis showed that 55.7% of the variance in the lifetime + current phenome factor was explained by increased atherogenicity, neglect and sexual abuse, while atherogenicity partially mediated the effects of neglect. Cluster analysis generated a cluster of patients with major dysmood disorder, which was externally validated by increased atherogenicity and characterized by increased scores of all clinical features.ConclusionsThe outcome of depression should not be represented as a binary variable (MDD or not), but rather as multiple dimensional scores based on biomarkers, ROI, subclinical depression traits, and lifetime and current phenome scores including suicidal behaviors.