bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceived stress in Chinese patients with coronary heart disease: a cross-sectional study
Authors: Gao Yifan , Hu Rong , Zhang Yingyue , Yuan Menghan , Xu Yong , Ma Jing 
Published: March 2022

ObjectiveStudies have shown that chronic stress is closely linked to the occurrence and development of cardiovascular disease. To date, few studies have focused on perceived stress in coronary heart diseases (CHD) patients and the possible factors influencing the stress. This study aims to investigate the perceived stress of patients with CHD and determine the individual attributes closely associated with it.DesignA cross-sectional study.ParticipatesA total of 2215 patients with CHD were enrolled and perceived stress was assessed with the Chinese version Perceived Stress Scale (CPSS). Participants were divided into two groups due to CPSS score and binary logistic regression was applied to analyse the factors that affected perceived stress level.ResultsThe mean CPSS score of Chinese patients with CHD was 27.16±6.35 Compared with participants who received senior middle school education or below, those with a university degree had a higher probability of high perceived stress (OR 1.453, 95% CI 1.206 to 1.750); this difference was more evident in participants with a master or doctoral degree (OR 1.928, 95% CI 1.290 to 2.882). Also engaging in mental labour (OR 1.389, 95% CI 1.144 to 1.686), having children (OR 2.226, 95% CI 1.098 to 4.515) and having a habit of risky alcohol consumption (OR 1.492, 95% CI 1.146 to 1.944) were associated with perceived stress.ConclusionPatients who had higher educational attainment, engaged in mental labour, had children, and had a habit of risky alcohol consumption were much easier to perceive the stress.
Effect of daily consumption of probiotic yoghurt on albumin to creatinine ratio, eGFR and metabolic parameters in patients with type 2 diabetes with microalbuminuria: study protocol for a randomised controlled clinical trial
Authors: Ghoreishy Seyed Mojtaba , Shirzad Nooshin , Nakhjavani Manouchehr , Esteghamati Alireza , Djafarian Kurosh , Esmaillzadeh Ahmad 
Published: March 2022

IntroductionTo alleviate clinical symptoms of diabetic nephropathy (DN), several dietary and non-dietary strategies have been suggested. Probiotic-enriched foods, through their effects on modulating microflora, might help these patients control the adverse effects. The current study will be done to examine the effects of probiotic yoghurt consumption on albumin to creatinine ratio, estimated glomerular filtration rate (eGFR) and metabolic parameters in patients with type 2 diabetes with nephropathy.Methods and analysisSixty patients with DN will be recruited in this study. After block matching for sex, body mass index and age, patients will be randomly assigned to receive 300 g/day probiotic yoghurt containing 106 CFU/g Lactobacillus acidophilus and Bifidobacterium lactis strains or 300 g/day plain yoghurt daily for 8 weeks. Weight, height and waist circumference will be measured at study baseline and after the intervention. Biochemical indicators including glycaemic measures (haemoglobin A1c (HbA1c), fasting blood sugar (FBS)), inflammatory markers (high sensitivity-C reactive protein), lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL)) and finally renal makers (creatinine, albumin to creatinine ratio, eGFR) will be assessed at study baseline and at the end of the trial.DiscussionImproving the condition of a person with DN is a serious clinical challenge. The use of probiotic supplements has been considered in these people, but the use of probiotic-enriched foods has received less attention.Trial registration numberIranian Registry of Clinical Trials (www.irct.ir) (IRCT20201125049491N1).
Treating hypertension with a pill containing very low doses of four antihypertensive agents compared with standard dose irbesartan
Authors: Eltayeb Abubaker , Khong Teck K 
Published: March 2022

AbstractCommentary on:Chow CK, Atkins ER, Hillis GS,et al. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial.Lancet. 2021;398:1043–52.Series co-ordinator:Dr Teck Khong, DTB Associate Editor Clinical Pharmacology, St George’s, University of London, UK
Airflow obstruction and small airway dysfunction following pulmonary tuberculosis: a cross-sectional survey
Authors: Xing Zhenzhen , Sun Tieying , Janssens Jean-Paul , Chai Di , Liu Weiming , Tong Yaqi , Wang Yuxia , Ma Yali , Pan Mingming , Cui Jia , Wang Chen , Guo YanFei 
Published: March 2022

ObjectivesPulmonary function impairment and chronic respiratory symptoms after tuberculosis are relatively common in low-income and middle-income countries. We aimed to estimate the impact of post-tuberculosis (post-TB) on pulmonary function.MethodsThis large cross-sectional, population-based study included subjects aged 15 years or older with technically acceptable postbronchodilator spirometry measurements. Post-TB was diagnosed on the basis of radiological evidence and/or medical history. Airflow obstruction was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal of Global Lung Function Initiative (GLI) lung function equations. Small airway dysfunction was diagnosed if at least two of the following indicators were less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50% or FEF 75%.ResultsIn this population sample (N=8680, mean age: 40.1 years), 610 (7.0% (95% CI 6.5 to 7.6) participants were post-TB. Post-TB subjects had more frequent respiratory symptoms (46.8% vs 28.3%). Among post-TB subjects, 130 (21.3% (95% CI 18.1 to 24.8)) had airflow obstruction; OR of airflow obstruction was significantly associated with post-TB after adjustment for other confounding factors (OR 1.31, 95% CI 1.05 to 1.62). Post-TB was also associated with small airway dysfunction (OR 1.28, 95% CI1.07 to 1.53), which was present in 297 (48.9% (95% CI 33.9 to 53.0)) post-TB subjects.ConclusionsOur findings support existing knowledge that post-TB is positively associated with pulmonary function impairment and make for frequent respiratory symptoms. Post-TB should be considered as a potentially important cause of airflow obstruction and respiratory symptoms in patients originating from countries with a high burden of tuberculosis.
Effects of caffeinated energy drinks on cardiovascular responses during exercise in healthy adults: a systematic review and meta-analysis of randomized controlled trials
Authors: Grinberg Nancy , Benkhedda Karima , Barber Jennifer , Krahn Andrew D. , La Vieille Sébastien 
Published: March 2022

The impact of caffeinated energy drinks (CEDs) on the cardiovascular (CV) response to exercise has not been well described. A systematic review and meta-analysis was conducted on the acute effects of CEDs on CV responses during dynamic, aerobic exercise in 296 healthy adult males (224) and females (72) in 21 randomized controlled trials. During exercise, there was an increase in heart rate (HR) (mean difference (MD), 2.86 bpm, 95% CI, 2.39–3.34 bpm, I2 = 0%, p < 0.00001), and systolic blood pressure (SBP) (MD, 9.02 mm Hg, 95% CI, 4.25–13.79 mm Hg, I2 = 0%, p = 0.0002) with consumption of CEDs, compared with controls, but diastolic blood pressure was similar. Insufficient data were available to evaluate rate pressure product (HR × SBP) and exercise-induced arrhythmia. Though changes to HR during exercise were modest, the significant increase in exercise SBP highlights the importance of directly assessing CV effects of CEDs with exercise, especially in individuals prone to hypertension.Novelty: Exercise SBP in healthy adults is significantly increased during exercise with the consumption of CEDs compared with controls, despite limited data. The direct assessment of CV effects of CEDs with exercise highlights the particular relevance to individuals prone to hypertension.
Search for low-energy signals from fast radio bursts with the Borexino detector
Authors: Appel S. , Bagdasarian Z. , Basilico D. , Bellini G. , Benziger J. , Biondi R. , Caccianiga B. , Calaprice F. , Caminata A. , Chepurnov A. , D’Angelo D. , Derbin A. , Giacinto A. Di , Marcello V. Di , Ding X. F. , Ludovico A. Di , Noto L. Di , Drachnev I. , Franco D. , Galbiati C. , Ghiano C. , Giammarchi M. , Goretti A. , Göttel A. S. , Gromov M. , Guffanti D. , Ianni Aldo , Ianni Andrea , Jany A. , Kobychev V. , Korga G. , Kumaran S. , Laubenstein M. , Litvinovich E. , Lombardi P. , Lomskaya I. , Ludhova L. , Lukyanchenko G. , Machulin I. , Martyn J. , Meroni E. , Miramonti L. , Misiaszek M. , Muratova V. , Nugmanov R. , Oberauer L. , Orekhov V. , Ortica F. , Pallavicini M. , Pelicci L. , Penek Ö. , Pietrofaccia L. , Pilipenko N. , Pocar A. , Raikov G. , Ranalli M. T. , Ranucci G. , Razeto A. , Re A. , Redchuk M. , Rossi N. , Schönert S. , Semenov D. , Settanta G. , Skorokhvatov M. , Singhal A. , Smirnov O. , Sotnikov A. , Tartaglia R. , Testera G. , Unzhakov E. , Vishneva A. , Vogelaar R. B. , Feilitzsch F. von , Wojcik M. , Wurm M. , Zavatarelli S. , Zhutikov I. , Zuber K. , Zuzel G. ,   Borexino Collaboration
Published: March 2022

AbstractThe search for neutrino events in correlation with 42 most intense fast radio bursts (FRBs) has been performed using the Borexino dataset from 05/2007 to 06/2021. We have searched for signals with visible energies above 250 keV within a time window of $$\pm \, 1000$$

±

1000

s corresponding to detection time of a particular FRB. We also applied an alternative approach based on searching for specific shapes of neutrino-electron scattering spectra in the full exposure data of the Borexino detector. In particular, two incoming neutrino spectra were considered: the monoenergetic line and the spectrum expected from supernovae. The same spectra were considered for electron antineutrinos detected through inverse beta-decay reaction. No statistically significant excess over the background was observed. As a result, the strongest upper limits on FRB-associated neutrino fluences of all flavors have been obtained in the 0.5–50 MeV neutrino energy range.
The semi-classical limit with a delta-prime potential
Authors: Cacciapuoti Claudio , Fermi Davide , Posilicano Andrea 
Published: March 2022

We consider the quantum evolution [Formula: see text] of a Gaussian coherent state [Formula: see text] localized close to the classical state [Formula: see text], where [Formula: see text] denotes a self-adjoint realization of the formal Hamiltonian [Formula: see text], with [Formula: see text] the derivative of Dirac’s delta distribution at [Formula: see text] and [Formula: see text] a real parameter. We show that in the semi-classical limit such a quantum evolution can be approximated (with respect to the [Formula: see text]-norm, uniformly for any [Formula: see text] away from the collision time) by [Formula: see text], where [Formula: see text], [Formula: see text] and [Formula: see text] is a suitable self-adjoint extension of the restriction to [Formula: see text], [Formula: see text], of ([Formula: see text] times) the generator of the free classical dynamics. While the operator [Formula: see text] here utilized is similar to the one appearing in our previous work [C. Cacciapuoti, D. Fermi and A. Posilicano, The semi-classical limit with a delta potential, Ann. Mat. Pura Appl. 200 (2021) 453–489], in the present case the approximation gives a smaller error: it is of order [Formula: see text], [Formula: see text], whereas it turns out to be of order [Formula: see text], [Formula: see text], for the delta potential. We also provide similar approximation results for both the wave and scattering operators.
Homoclinic Boundary-Saddle Bifurcations in Planar Nonsmooth Vector Fields
Authors: Andrade Kamila da S. , Jeffrey Mike R. , Martins Ricardo M. , Teixeira Marco A. 
Published: March 2022

In a smooth dynamical system, a homoclinic connection is an orbit connecting a saddle equilibrium to itself. Under perturbation, homoclinics are associated with bifurcations of periodic orbits, and chaos in higher dimensions. Homoclinic connections in nonsmooth systems are complicated by their interactions with discontinuities in their vector fields. A connection may involve a regular saddle outside a discontinuity set, or a pseudo-saddle on a discontinuity set, with segments of the connection to cross or slide along the discontinuity. Even the simplest case of connection to a regular saddle, which hits a discontinuity as a parameter is varied, is surprisingly complex. In this paper, we construct bifurcation diagrams for nonresonant saddles in the plane, unfolding the homoclinic connection to a boundary saddle in a nonsmooth dynamical system. As an application, we exhibit such diagrams for a model of a forced pendulum.
Building a Fast and Efficient LSM-tree Store by Integrating Local Storage with Cloud Storage
Authors: Xu Peng , Zhao Nannan , Wan Jiguang , Liu Wei , Chen Shuning , Zhou Yuanhui , Albahar Hadeel , Liu Hanyang , Tang Liu , Tan Zhihu 
Published: March 2022

The explosive growth of modern web-scale applications has made cost-effectiveness a primary design goal for their underlying databases. As a backbone of modern databases, LSM-tree based key–value stores (LSM store) face limited storage options. They are either designed for local storage that is relatively small, expensive, and fast or for cloud storage that offers larger capacities at reduced costs but slower. Designing an LSM store by integrating local storage with cloud storage services is a promising way to balance the cost and performance. However, such design faces challenges such as data reorganization, metadata overhead, and reliability issues. In this article, we propose
RocksMash
, a fast and efficient LSM store that uses local storage to store frequently accessed data and metadata while using cloud to hold the rest of the data to achieve cost-effectiveness. To improve metadata space-efficiency and read performance,
RocksMash
uses an LSM-aware persistent cache that stores metadata in a space-efficient way and stores popular data blocks by using compaction-aware layouts. Moreover,
RocksMash
uses an extended write-ahead log for fast parallel data recovery. We implemented
RocksMash
by embedding these designs into RocksDB. The evaluation results show that
RocksMash
improves the performance by up to 1.7

\( \times \)

compared to the state-of-the-art schemes and delivers high reliability, cost-effectiveness, and fast recovery.
GENESIS: Gene-Specific Machine Learning Models for Variants of Uncertain Significance Found in Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome-Associated Genes
Authors: Draelos Rachel L. , Ezekian Jordan E. , Zhuang Farica , Moya-Mendez Mary E. , Zhang Zhushan , Rosamilia Michael B. , Manivannan Perathu K.R. , Henao Ricardo , Landstrom Andrew P. 
Published: March 2022

Background:

Cardiac channelopathies such as catecholaminergic polymorphic tachycardia and long QT syndrome predispose patients to fatal arrhythmias and sudden cardiac death. As genetic testing has become common in clinical practice, variants of uncertain significance (VUS) in genes associated with catecholaminergic polymorphic ventricular tachycardia and long QT syndrome are frequently found. The objective of this study was to predict pathogenicity of catecholaminergic polymorphic ventricular tachycardia-associated
RYR2
VUS and long QT syndrome-associated VUS in
KCNQ1
,
KCNH2
, and
SCN5A
by developing gene-specific machine learning models and assessing them using cross-validation, cellular electrophysiological data, and clinical correlation.

Methods:

The GENe-specific EnSemble grId Search framework was developed to identify high-performing machine learning models for
RYR2
,
KCNQ1
,
KCNH2
, and
SCN5A
using variant- and protein-specific inputs. Final models were applied to datasets of VUS identified from ClinVar and exome sequencing. Whole cell patch clamp and clinical correlation of selected VUS was performed.

Results:

The GENe-specific EnSemble grId Search models outperformed alternative methods, with area under the receiver operating characteristics up to 0.87, average precisions up to 0.83, and calibration slopes as close to 1.0 (perfect) as 1.04. Blinded voltage-clamp analysis of HEK293T cells expressing 2 predicted pathogenic variants in
KCNQ1
each revealed an ≈80% reduction of peak Kv7.1 current compared with WT. Normal Kv7.1 function was observed in KCNQ1-V241I HEK cells as predicted. Though predicted benign, loss of Kv7.1 function was observed for KCNQ1-V106D HEK cells. Clinical correlation of 9/10 variants supported model predictions.

Conclusions:
Gene-specific machine learning models may have a role in post-genetic testing diagnostic analyses by providing high performance prediction of variant pathogenicity.
Generalizability of Cardiovascular Disease Clinical Prediction Models: 158 Independent External Validations of 104 Unique Models
Authors: Gulati Gaurav , Upshaw Jenica , Wessler Benjamin S. , Brazil Riley J. , Nelson Jason , van Klaveren David , Lundquist Christine M. , Park Jinny G. , McGinnes Hannah , Steyerberg Ewout W. , Van Calster Ben , Kent David M. 
Published: March 2022

Background:
While clinical prediction models (CPMs) are used increasingly commonly to guide patient care, the performance and clinical utility of these CPMs in new patient cohorts is poorly understood.

Methods:
We performed 158 external validations of 104 unique CPMs across 3 domains of cardiovascular disease (primary prevention, acute coronary syndrome, and heart failure). Validations were performed in publicly available clinical trial cohorts and model performance was assessed using measures of discrimination, calibration, and net benefit. To explore potential reasons for poor model performance, CPM-clinical trial cohort pairs were stratified based on relatedness, a domain-specific set of characteristics to qualitatively grade the similarity of derivation and validation patient populations. We also examined the model-based C-statistic to assess whether changes in discrimination were because of differences in case-mix between the derivation and validation samples. The impact of model updating on model performance was also assessed.

Results:

Discrimination decreased significantly between model derivation (0.76 [interquartile range 0.73–0.78]) and validation (0.64 [interquartile range 0.60–0.67],
P
<0.001), but approximately half of this decrease was because of narrower case-mix in the validation samples. CPMs had better discrimination when tested in related compared with distantly related trial cohorts. Calibration slope was also significantly higher in related trial cohorts (0.77 [interquartile range, 0.59–0.90]) than distantly related cohorts (0.59 [interquartile range 0.43–0.73],
P
=0.001). When considering the full range of possible decision thresholds between half and twice the outcome incidence, 91% of models had a risk of harm (net benefit below default strategy) at some threshold; this risk could be reduced substantially via updating model intercept, calibration slope, or complete re-estimation.

Conclusions:
There are significant decreases in model performance when applying cardiovascular disease CPMs to new patient populations, resulting in substantial risk of harm. Model updating can mitigate these risks. Care should be taken when using CPMs to guide clinical decision-making.
Loss of Endothelial Cytochrome P450 Reductase Induces Vascular Dysfunction in Mice
Authors: Malacarne Pedro Felipe , Ratiu Corina , Gajos-Draus Anna , Müller Niklas , Lopez Melina , Pflüger-Müller Beatrice , Ding Xinxin , Warwick Timothy , Oo James , Siragusa Mauro , Angioni Carlo , Günther Stefan , Weigert Andreas , Geißlinger Gerd , Lütjohann Dieter , Schunck Wolf-Hagen , Fleming Ingrid , Brandes Ralf P. , Rezende Flávia 
Published: March 2022

Background:
POR (cytochrome P450 reductase) provides electrons for the catalytic activity of the CYP (cytochrome P450) monooxygenases. CYPs are dual-function enzymes as they generate protective vasoactive mediators derived from polyunsaturated fatty acids but also reactive oxygen species. It is not known in which conditions the endothelial POR/CYP system is beneficial versus deleterious. Here, the activity of all CYP enzymes was eliminated in the vascular endothelium to examine its impact on vascular function.

Methods:

An endothelial-specific, tamoxifen-inducible POR knockout mouse (ecPOR
−
/−
) was generated. Vascular function was studied by organ chamber experiments. eNOS (endothelial nitric oxide synthase) activity was accessed by heavy arginine/citrulline LC-MS/MS detection and phosphorylation of serine1177 in aortic rings. CYP-derived epoxyeicosatrienoic acids and prostanoids were measured by LC-MS/MS. Gene expression of aorta and endothelial cells was profiled by RNA sequencing. Blood pressure was measured by telemetry.

Results:

Acetylcholine-induced endothelium-dependent relaxation was attenuated in isolated vessels of ecPOR
−/−
as compared with control mice. Additionally, ecPOR
−/−
mice had attenuated eNOS activity and eNOS/AKT phosphorylation. POR deletion reduced endothelial stores of CYP-derived epoxyeicosatrienoic acids but increased vascular prostanoids. This phenomenon was paralleled by the induction of genes implicated in eicosanoid generation. In response to Ang II (angiotensin II) infusion, blood pressure increased significantly more in ecPOR
−
/−
mice. Importantly, the cyclooxygenase inhibitor Naproxen selectively lowered the Ang II–induced hypertension in ecPOR
−
/−
mice.

Conclusions:
POR expression in endothelial cells maintains eNOS activity and its loss results in an overactivation of the vasoconstrictor prostanoid system. Through these mechanisms, loss of endothelial POR induces vascular dysfunction and hypertension.