bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis
Authors: Veres Boglárka , Fehérvári Péter , Engh Marie Anne , Hegyi Péter , Gharehdaghi Sara , Zima Endre , Duray Gábor , Merkely Béla , Kosztin Annamária 
Published: September 2023

Abstract

Aims
This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades.

Methods and results
PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76–0.94; P &lt; 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80–0.87; P &lt; 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79–1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96–1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients’ characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time.

Conclusion
The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.
Hyaluronan synthases; mechanisms, myths, & mysteries of three types of unique bifunctional glycosyltransferases
Authors: DeAngelis Paul L , Zimmer Jochen 
Published: September 2023

Abstract
Hyaluronan (HA), the essential [-3-GlcNAc-1-β-4-GlcA-1-β-]n matrix polysaccharide in vertebrates and molecular camouflage coating in select pathogens, is polymerized by “HA synthase” (HAS) enzymes. The first HAS identified three decades ago opened the window for new insights and biotechnological tools. This review discusses current understanding of HA biosynthesis, its biotechnological utility, and addresses some misconceptions in the literature.
HASs are fascinating enzymes that polymerize two different UDP-activated sugars via different glycosidic linkages. Therefore, these catalysts were the first examples to break the “one enzyme/one sugar transferred” dogma. Three distinct types of these bifunctional glycosyltransferases (GTs) with disparate architectures and reaction modes are known. Based on biochemical and structural work, we present an updated classification system. Class I membrane-integrated HASs employ a processive chain elongation mechanism and secrete HA across the plasma membrane. This complex operation is accomplished by functionally integrating a cytosolic catalytic domain with a channel-forming transmembrane region. Class I enzymes, containing a single GT family-2 (GT-2) module that adds both monosaccharide units to the nascent chain, are further subdivided into two groups that construct the polymer with opposite molecular directionalities: Class I-R and I-NR elongate the HA polysaccharide at either the reducing or the non-reducing end, respectively. In contrast, Class II HASs are membrane-associated peripheral synthases with a non-processive, non-reducing end elongation mechanism using two independent GT-2 modules (one for each type of monosaccharide) and require a separate secretion system for HA export. We discuss recent mechanistic insights into HA biosynthesis that promise biotechnological benefits and exciting engineering approaches.
Effects of vertical integration on the healthcare system in China: a systematic review and meta-analysis
Authors: Wang Xin , Yang Enming , Zheng Caiyun , Yuan Shasha 
Published: September 2023

Abstract
Vertical integration is one possible way to improve the performance of a healthcare system; however, its effects are inconsistent, and there is a lack of evidence from undeveloped nations. This study aims to systematically review the evidence regarding effects of vertical integration on healthcare systems in China. We searched PubMed, Embase, Cochrane Library, Web of Science, ProQuest Health & Medicine Collection, China Knowledge Resource Integrated Database and Wanfang databases from April 2009 (initiation of new healthcare reform) to May 2021 for randomized controlled trials (RCTs), controlled before and after (CBA) trials, cohort studies and interrupted time series (ITS) trials. Vertical integration in the included studies must involve both primary health institutions and secondary or tertiary hospitals. After screening 3109 records, we ultimately analysed 47 studies, including 27 CBA trials, 18 RCTs and 2 ITS trials. The narrative synthesis shows that all but three studies indicated that vertical integration improved efficiency (utilization and cost of health services), quality of public health services and medical services, health provider-centred outcomes (knowledge and skill) and patient-centred outcomes (patients’ clinical outcomes, behaviour and satisfaction). Despite the heterogeneity of vertical integration interventions across different studies, the meta-analysis reveals that it lowered diastolic blood pressure (mean difference (MD) −8.41, 95% confidence interval (CI) −15.18 to −1.65) and systolic blood pressure (MD-5.83, 95% CI −9.25 to −2.40) among hypertension patients, and it lowered HbA1c levels (MD −1.95, 95% CI −2.69 to −1.21), fasting blood glucose levels (MD −1.02, 95% CI −1.53 to −0.50) and 2-hour postprandial blood glucose levels (MD −1.78, 95% CI −2.67 to −0.89). The treatment compliance behaviour was improved for hypertension participants (risk ratio (RR) 1.08, 95% CI 1.04–1.13) and for diabetes patients (RR 1.32, 95% CI 1.08–1.61). Vertical integration in China can improve efficiency, quality of care, health provider-centred outcomes and patient-centred outcomes, but high-quality original studies are highly needed.
Translation reinitiation in c.453delC frameshift mutation of KCNH2 producing functional hERG K+ channels with mild dominant negative effect in the heterozygote patient-derived iPSC cardiomyocytes
Authors: Park Na Kyeong , Park Soon-Jung , Park Yun-Gwi , Moon Sung-Hwan , Woo JooHan , Kim Hyun Jong , Kim Sung Joon , Choi Seong Woo 
Published: September 2023

Abstract
The c.453delC (p.Thr152Profs*14) frameshift mutation in KCNH2 is associated with an elevated risk of Long QT syndrome (LQTS) and fatal arrhythmia. Nevertheless, the loss-of-function mechanism underlying this mutation remains unexplored and necessitates an understanding of electrophysiology. To gain insight into the mechanism of the LQT phenotype, we conducted whole-cell patch-clamp and immunoblot assays, utilizing both a heterologous expression system and patient-derived induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) with 453delC-KCNH2. We also explored the site of translational reinitiation by employing LC/MS mass spectrometry. Contrary to the previous assumption of early termination of translation, the findings of this study indicate that the 453delC-KCNH2 leads to an N-terminally truncated hERG channel, a potential from a non-canonical start codon, with diminished expression and reduced current (IhERG). The co-expression with wildtype KCNH2 produced heteromeric hERG channel with mild dominant-negative effect. Additionally, the heterozygote patient-derived iPSC-CMs exhibited prolonged action potential duration and reduced IhERG, which was ameliorated with the use of a hERG activator, PD-118057. The results of our study offer novel insights into the mechanisms involved in congenital LQTS associated with the 453delC mutation of KCNH2. The mutant results in the formation of less functional N-terminal-truncated channels with reduced amount of membrane expression. A hERG activator is capable of correcting abnormalities in both the heterologous expression system and patient-derived iPSC-CMs.
Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcomes
Authors: Selvaratnam Roshan J , Sovio Ulla , Cook Emma , Gaccioli Francesca , Charnock-Jones D Stephen , Smith Gordon C S 
Published: September 2023

Abstract

Background
In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes.

Methods
We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age. Objective smoking status was defined based on detectable cotinine levels at each time point and objective caffeine exposure was based on tertiles of paraxanthine levels at each time point. We used logistic and linear regression to examine the association between cotinine, paraxanthine and the risk of pre-eclampsia, spontaneous pre-term birth (sPTB), fetal growth restriction (FGR), gestational diabetes mellitus and birthweight.

Results
There were 914 and 915 women in the smoking and caffeine analyses, respectively. Compared with no exposure to smoking, consistent exposure to smoking was associated with an increased risk of sPTB [adjusted odds ratio (aOR) = 2.58, 95% CI: 1.14 to 5.85)] and FGR (aOR = 4.07, 95% CI: 2.14 to 7.74) and lower birthweight (β = –387 g, 95% CI: –622 g to –153 g). On univariate analysis, consistently high levels of paraxanthine were associated with an increased risk of FGR but that association attenuated when adjusting for maternal characteristics and objective—but not self-reported—smoking status.

Conclusions
Based on objective data, consistent exposure to smoking throughout pregnancy was strongly associated with sPTB and FGR. High levels of paraxanthine were not independently associated with any of the studied outcomes and were confounded by smoking.
Risk of diabetes and cardiovascular diseases in women with vaginal bleeding before 20 gestational weeks: Danish population-based cohort study
Authors: Dudukina Elena , Horváth-Puhó Erzsébet , Sørensen Henrik Toft , Ehrenstein Vera 
Published: September 2023

Abstract

Background
Women’s reproductive health is associated with cardiovascular morbidity. However, an association of vaginal bleeding (VB) in pregnancy with diabetes and cardiovascular outcomes has scarcely been investigated.

Methods
We conducted a population-based cohort study in Denmark (1994–2018). Using nationwide registries, among 903 327 women we identified 1 901 725 pregnancies: 39 265 ended in childbirth and were affected by VB; 1 389 285 ended in childbirth and were unaffected by VB; 333 785 ended in a termination, and 139 390 ended in a miscarriage. The outcomes were diabetes types 1 and 2, hypertension, ischaemic heart disease including myocardial infarction, atrial fibrillation or flutter, heart failure and ischaemic and haemorrhagic stroke. We computed incidence rates and hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, calendar year of pregnancy end, morbidities and reproductive and socioeconomic factors, using inverse probability of treatment-weighted Cox proportional hazards regression.

Results
In analyses of VB-affected vs VB-unaffected pregnancies, aHRs were 1.15 (1.03–1.28) for diabetes type 1, 1.19 (1.13–1.26) for diabetes type 2, 1.19 (1.14–1.25) for hypertension, 1.26 (1.16–1.37) for ischaemic heart disease, 1.21 (1.03–1.42) for myocardial infarction, 1.32 (1.14–1.51) for atrial fibrillation or flutter and 1.23 (0.99–1.52) for heart failure. aHRs were 1.41 (1.26–1.57) and 1.46 (1.23–1.72) for ischaemic and haemorrhagic stroke, respectively. When contrasting VB-affected pregnancies with terminations, aHRs were up to 1.3-fold increased for diabetes and hypertension; however, when contrasting VB-affected pregnancies with miscarriages, estimates were below or close to the null value.

Conclusions
Women’s risks of diabetes and cardiovascular outcomes later in life were increased following VB-affected vs VB-unaffected pregnancy or termination, but not following VB-affected pregnancy vs miscarriage.
Deep sequential neural network models improve stratification of suicide attempt risk among US veterans
Authors: Martinez Carianne , Levin Drew , Jones Jessica , Finley Patrick D , McMahon Benjamin , Dhaubhadel Sayera , Cohn Judith ,   Million Veteran Program,   MVP Suicide Exemplar Workgroup, Oslin David W , Kimbrel Nathan A , Beckham Jean C 
Published: September 2023

Abstract

Objective
To apply deep neural networks (DNNs) to longitudinal EHR data in order to predict suicide attempt risk among veterans. Local explainability techniques were used to provide explanations for each prediction with the goal of ultimately improving outreach and intervention efforts.

Materials and methods
The DNNs fused demographic information with diagnostic, prescription, and procedure codes. Models were trained and tested on EHR data of approximately 500 000 US veterans: all veterans with recorded suicide attempts from April 1, 2005, through January 1, 2016, each paired with 5 veterans of the same age who did not attempt suicide. Shapley Additive Explanation (SHAP) values were calculated to provide explanations of DNN predictions.

Results
The DNNs outperformed logistic and linear regression models in predicting suicide attempts. After adjusting for the sampling technique, the convolutional neural network (CNN) model achieved a positive predictive value (PPV) of 0.54 for suicide attempts within 12 months by veterans in the top 0.1% risk tier. Explainability methods identified meaningful subgroups of high-risk veterans as well as key determinants of suicide attempt risk at both the group and individual level.

Discussion and conclusion
The deep learning methods employed in the present study have the potential to significantly enhance existing suicide risk models for veterans. These methods can also provide important clues to explore the relative value of long-term and short-term intervention strategies. Furthermore, the explainability methods utilized here could also be used to communicate to clinicians the key features which increase specific veterans’ risk for attempting suicide.
Domestication is associated with increased interspecific hybrid compatibility in landfowl (order: Galliformes)
Authors: Alfieri James M , Hingoranee Reina , Athrey Giridhar N , Blackmon Heath 
Published: September 2023

Abstract
Some species are able to hybridize despite being exceptionally diverged. The causes of this variation in accumulation of reproductive isolation remain poorly understood, and domestication as an impetus or hindrance to reproductive isolation remains to be characterized. In this study, we investigated the role of divergence time, domestication, and mismatches in morphology, habitat, and clutch size among hybridizing species on reproductive isolation in the bird order Galliformes. We compiled and analyzed hybridization occurrences from literature and recorded measures of postzygotic reproductive isolation. We used a text-mining approach leveraging a historical aviculture magazine to quantify the degree of domestication across species. We obtained divergence time, morphology, habitat, and clutch size data from open sources. We found 123 species pairs (involving 77 species) with known offspring fertility (sterile, only males fertile, or both sexes fertile). We found that divergence time and clutch size were significant predictors of reproductive isolation (McFadden’s Pseudo-R2 = 0.59), but not habitat or morphological mismatch. Perhaps most interesting, we found a significant relationship between domestication and reproductive compatibility after correcting for phylogeny, removing extreme values, and addressing potential biases (F1,74 = 5.43, R2 = 0.06, P-value = 0.02). We speculate that the genetic architecture and disruption in selective reproductive regimes associated with domestication may impact reproductive isolation, causing domesticated species to be more reproductively labile.
Lysosomal control of dendritic cell function
Authors: Yang Jia , Rong Shan-Jie , Zhou Hai-Feng , Yang Chao , Sun Fei , Li Jun-Yi 
Published: September 2023

AbstractLysosomal compartments undergo extensive remodeling during dendritic cell (DC) activation to meet the dynamic functional requirements of DCs. Instead of being regarded as stationary and digestive organelles, recent studies have increasingly appreciated the versatile roles of lysosomes in regulating key aspects of DC biology. Lysosomes actively control DC motility by linking calcium efflux to the actomyosin contraction, while enhanced DC lysosomal membrane permeability contributes to the inflammasome activation. Besides, lysosomes provide a platform for the transduction of innate immune signaling and the intricate host-pathogen interplay. Lysosomes and lysosome-associated structures are also critically engaged in antigen presentation and cross-presentation processes, which are pivotal for the induction of antigen-specific adaptive immune response. Through the current review, we emphasize that lysosome targeting strategies serve as vital DC-based immunotherapies in fighting against tumor, infectious diseases, and autoinflammatory disorders.
Artificial intelligence–based image analysis in clinical testing: lessons from cervical cancer screening
Authors: Egemen Didem , Perkins Rebecca B , Cheung Li C , Befano Brian , Rodriguez Ana Cecilia , Desai Kanan , Lemay Andreanne , Ahmed Syed Rakin , Antani Sameer , Jeronimo Jose , Wentzensen Nicolas , Kalpathy-Cramer Jayashree , De Sanjose Silvia , Schiffman Mark 
Published: September 2023

Abstract
Novel screening and diagnostic tests based on artificial intelligence (AI) image recognition algorithms are proliferating. Some initial reports claim outstanding accuracy followed by disappointing lack of confirmation, including our own early work on cervical screening. This is a presentation of lessons learned, organized as a conceptual step-by-step approach to bridge the gap between the creation of an AI algorithm and clinical efficacy. The first fundamental principle is specifying rigorously what the algorithm is designed to identify and what the test is intended to measure (eg, screening, diagnostic, or prognostic). Second, designing the AI algorithm to minimize the most clinically important errors. For example, many equivocal cervical images cannot yet be labeled because the borderline between cases and controls is blurred. To avoid a misclassified case-control dichotomy, we have isolated the equivocal cases and formally included an intermediate, indeterminate class (severity order of classes: case&gt;indeterminate&gt;control). The third principle is evaluating AI algorithms like any other test, using clinical epidemiologic criteria. Repeatability of the algorithm at the borderline, for indeterminate images, has proven extremely informative. Distinguishing between internal and external validation is also essential. Linking the AI algorithm results to clinical risk estimation is the fourth principle. Absolute risk (not relative) is the critical metric for translating a test result into clinical use. Finally, generating risk-based guidelines for clinical use that match local resources and priorities is the last principle in our approach. We are particularly interested in applications to lower-resource settings to address health disparities. We note that similar principles apply to other domains of AI-based image analysis for medical diagnostic testing.
Specific antioxidant enzymes are involved in the freeze-thawing response of industrial baker’s yeasts
Authors: Kronberg María F , Terlizzi Natalia L , Galvagno Miguel A 
Published: September 2023

Abstract
In this study, the biochemical basis of resistance to slow freezing and thawing (F-T) stress was explored in two baker yeast industrial strains of Saccharomyces cerevisiae that presented differential tolerance to freezing in order to be in the frozen bakery industry. Strain Y8, used commercially in sweet baking doughs, exhibited greater stress tolerance than Y9, a strain employed in regular doughs. Survival of Y8 was higher than that of Y9 (30% vs 12%) after F-T or other reactive oxygen species (ROS) inducing stresses compared to their non-stressed controls. The superior F-T tolerance of Y8 was related to its lower ROS accumulation capacity, determined by fluorometry in cell-free extracts and in vivo, by fluorescence microscopy upon F-T, being Y8 ROS accumulation 2-fold lower than that of Y9. That, in turn, could be positively associated with Y8’s higher constitutive activities of cytosolic catalase (CAT) and superoxide dismutase by a significant activation (25%) of Y8 CAT after F-T. That would complement the protective effects of other protectant molecules like trehalose, present at high concentration in this strain.
Myocardial Ischemia
Authors: Bursian Alberto , Mohamed Basma 
Published: September 2023

Abstract
Perioperative myocardial ischemia or myocardial injury is the most common cause of perioperative cardiac complications in patients undergoing noncardiac surgery. Perioperative cardiac complications include cardiac death, heart failure, ventricular tachycardia, and nonfatal myocardial infarction. These complications occur in up to 5% of noncardiac surgery patients. Also, there is a larger group of patients who have a rise in troponin, a biomarker of cardiac injury, but no symptoms and no evidence of myocardial ischemia on electrocardiogram. In this chapter, we will focus on the evaluation and management of perioperative myocardial ischemia or infarction in patients undergoing noncardiac surgery. The etiology of perioperative myocardial ischemia can be plaque rupture versus supply-demand mismatch as a result of different factors including the stress of surgery and hemodynamic changes. Plaque rupture as a result may present as ST-elevation myocardial infarction, and this would warrant urgent involvement of the cardiologists for a possible intervention. Perioperative non-ST-elevation myocardial infarction may result from supply-demand mismatch. This would need modification of risk factors perioperatively and can extend to postoperative care that includes observation and possible intervention. As a result of the high risk of perioperative cardiac morbidity, patients are better screened using different risk assessment tools and referred to preoperative assessment based on their risk factors and the risk of surgery. It is advised to be proactive in the management of patients at high risk of perioperative major adverse cardiac events.