bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men
Authors: Manikpurage Hasanga D. , Eslami Aida , Perrot Nicolas , Li Zhonglin , Couture Christian , Mathieu Patrick , Bossé Yohan , Arsenault Benoit J. , Thériault Sébastien 
Published: October 2021

Background:
Several risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.

Methods:

A PRS
CAD
including the weighted effects of >1.14 million single nucleotide polymorphisms associated with CAD was calculated in UK Biobank (n=408 422), using LDpred. Cox regressions were performed, stratified by age quartiles and sex, for incident myocardial infarction (MI) and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRS
CAD
to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI
0.02
) and continuous NRI (NRI
>0
).

Results:

From 7746 incident MI cases and 393 725 controls, hazard ratio for MI reached 1.53 (95% CI, 1.49–1.56;
P
=2.69×10
−296
) per SD increase of PRS
CAD
. PRS
CAD
was significantly associated with MI in both sexes, with a stronger association in men (interaction
P
=0.002), particularly in those aged between 40 and 51 years (hazard ratio, 2.00 [95% CI, 1.86–2.16],
P
=1.93×10
−72
). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI
0.02
, 0.199 [95% CI, 0.157–0.248] and NRI
>0
, 0.602 [95% CI, 0.525–0.683]). From 23 982 deaths, hazard ratio for mortality was 1.08 (95% CI, 1.06–1.09;
P
=5.46×10
−30
) per SD increase of PRS
CAD
, with a stronger association in men (interaction
P
=1.60×10
−6
).

Conclusions:

Our PRS
CAD
predicts MI incidence and all-cause mortality, especially in men aged between 40 and 51 years. PRS could optimize the identification and management of individuals at risk for CAD.
Mediating Capitalism’s ‘Rules of Reproduction’ with Historical Agency
Authors: Evans Jessica 
Published: October 2021

Abstract
This article responds to Samuel Knafo and Benno Teschke’s recent critique of Political Marxism and their proposal for an alternative, ‘radical agency-centred’ historicism. While sympathetic to the critiques raised by the authors, I am less convinced by the conclusions they reach. Rather than abandon Political Marxism altogether, I argue that there remains much of value in the tradition. Through an analysis of the differential path of capitalist development in settler-colonial Canada, I suggest that bringing the methodological insights of Uneven and Combined Development to bear on the theoretical material of Political Marxism can alleviate the problems identified by the authors.
Why the All-Affected Principle Is Groundless
Authors: Bengtson Andreas , Lippert-Rasmussen Kasper 
Published: October 2021

Abstract
The all-affected principle is a widely accepted solution to the problem of constituting the demos. Despite its popularity, a basic question in relation to the principle has not received much attention: why does the fact that an individual is affected by a certain decision ground a right to inclusion in democratic decision-making about that matter? An answer to this question must include a reason that explains why an affected individual should be included because she is affected. We identify three such reasons in the literature – to wit, interest protection, self-government and welfare – and show why they all fail. We then propose two alternative reasons, equal relations and fairness, and show why they are also deficient. Surprisingly, the all-affected principle then appears groundless, which supports withholding belief in the all-affected principle or(/and) investing future research in identifying the thus-far unidentified reason why being affected grounds a claim to inclusion.
Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature
Authors: Brignardello-Petersen Romina , El Alayli Abdallah , Husainat Nedaa , Kalot Mohamad A. , Shahid Shaneela , Aljabirii Yazan , Britt Alec , Alturkmani Hani , El-Khechen Hussein , Motaghi Shahrzad , Roller John , Abdul-Kadir Rezan , Couper Susie , Kouides Peter , Lavin Michelle , Ozelo Margareth C. , Weyand Angela , James Paula D. , Connell Nathan T. , Flood Veronica H. , Mustafa Reem A. 
Published: October 2021

Abstractvon Willebrand disease (VWD) disproportionately affects women because of the potential for heavy menstrual bleeding (HMB), delivery complications, and postpartum hemorrhage (PPH). To systematically synthesize the evidence regarding first-line management of HMB, treatment of women requiring or desiring neuraxial analgesia, and management of PPH. We searched Medline and EMBASE through October 2019 for randomized trials, comparative observational studies, and case series comparing the effects of desmopressin, hormonal therapy, and tranexamic acid (TxA) on HMB; comparing different von Willebrand factor (VWF) levels in women with VWD who were undergoing labor and receiving neuraxial anesthesia; and measuring the effects of TxA on PPH. We conducted duplicate study selection, data abstraction, and appraisal of risk of bias. Whenever possible, we conducted meta-analyses. We assessed the quality of the evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We included 1 randomized trial, 3 comparative observational studies, and 10 case series. Moderate-certainty evidence showed that desmopressin resulted in a smaller reduction of menstrual blood loss (difference in mean change from baseline, 41.6 [95% confidence interval, 16.6-63.6] points in a pictorial blood assessment chart score) as compared with TxA. There was very-low-certainty evidence about how first-line treatments compare against each other, the effects of different VWF levels in women receiving neuraxial anesthesia, and the effects of postpartum administration of TxA. Most of the evidence relevant to the gynecologic and obstetric management of women with VWD addressed by most guidelines is very low quality. Future studies that address research priorities will be key when updating such guidelines.
Systemic administration of choline acetyltransferase decreases blood pressure in murine hypertension
Authors: Stiegler Andrew , Li Jian-Hua , Shah Vivek , Tsaava Tea , Tynan Aisling , Yang Huan , Tamari Yehuda , Brines Michael , Tracey Kevin J. , Chavan Sangeeta S. 
Published: October 2021

AbstractAcetylcholine (ACh) decreases blood pressure by stimulating endothelium nitric oxide-dependent vasodilation in resistance arterioles. Normal plasma contains choline acetyltransferase (ChAT) and its biosynthetic product ACh at appreciable concentrations to potentially act upon the endothelium to affect blood pressure. Recently we discovered a T-cell subset expressing ChAT (TChAT), whereby genetic ablation of ChAT in these cells produces hypertension, indicating that production of ACh by TChAT regulates blood pressure. Accordingly, we reasoned that increasing systemic ChAT concentrations might induce vasodilation and reduce blood pressure. To evaluate this possibility, recombinant ChAT was administered intraperitoneally to mice having angiotensin II-induced hypertension. This intervention significantly and dose-dependently decreased mean arterial pressure. ChAT-mediated attenuation of blood pressure was reversed by administration of the nitric oxide synthesis blocker l-nitro arginine methyl ester, indicating ChAT administration decreases blood pressure by stimulating nitic oxide dependent vasodilation, consistent with an effect of ACh on the endothelium. To prolong the half life of circulating ChAT, the molecule was modified by covalently attaching repeating units of polyethylene glycol (PEG), resulting in enzymatically active PEG-ChAT. Administration of PEG-ChAT to hypertensive mice decreased mean arterial pressure with a longer response duration when compared to ChAT. Together these findings suggest further studies are warranted on the role of ChAT in hypertension.
Primary high-grade serous ovarian cancer cells are sensitive to senescence induced by carboplatin and paclitaxel in vitro
Authors: Uruski Paweł , Sepetowska Agnieszka , Konieczna Corinna , Pakuła Martyna , Wyrwa Michał , Tussupkaliyev Akylbek , Tykarski Andrzej , Mikuła-Pietrasik Justyna , Książek Krzysztof 
Published: October 2021

Abstract
Background
Various types of normal and cancer cells undergo senescence in response to carboplatin and paclitaxel, which are considered the gold standard treatments in ovarian cancer management. Surprisingly, the effect of these drugs on ovarian cancer cell senescence remained unknown.

Methods
The experiments were conducted on primary high-grade serous ovarian cancer cells. Molecular markers of senescence were evaluated using cytochemistry and immunofluorescence. Cell cycle distribution was analyzed using flow cytometry. Expression of cyclins and signaling pathways was tested using western blot. Telomere length and telomerase activity were measured using qPCR, and the colocalization of telomeres with DNA damage foci using immuno-FISH. Oxidative stress-related parameters were quantified using appropriate fluorescence probes. Production of cancerogenic agents was analyzed using qPCR and ELISA.

Results
Carboplatin applied with paclitaxel induces senescence of ovarian cancer cells in vitro. This activity was reflected by permanent G2/M growth arrest, a high fraction of cells expressing senescence biomarkers (SA-β-Gal and γ-H2A.X), upregulated expression of p16, p21, and p53 cell cycle inhibitors, and decreased expression of cyclin B1. Neither telomere length nor telomerase activity changed in the senescent cells, and the majority of DNA damage was localized outside telomeres. Moreover, drug-treated cancer cells exhibited increased production of STAT3 protein, overproduced superoxide and peroxides, and increased mitochondrial mass. They were also characterized by upregulated ANG1, CCL11, IL-6, PDGF-D, TIMP-3, TSP-1, and TGF-β1 at the mRNA and/or protein level.

Conclusions
Our findings imply that conventional chemotherapy may elicit senescence in ovarian cancer cells, which may translate to the development of a cancer-promoting phenotype, despite the inability of these cells to divide.
Risk factors for mortality in patients undergoing continuous renal replacement therapy after cardiac surgery
Authors: Liu Chang , Zhang Hai-Tao , Yue Li-Jun , Li Ze-Shi , Pan Ke , Chen Zhong , Gu Su-Ping , Pan Tuo , Pan Jun , Wang Dong-Jin 
Published: October 2021

Abstract
Background
To investigate the risk factors for mortality in patients with acute kidney injury requiring continuous renal replacement therapy (AKI-CRRT) after cardiac surgery.

Methods
In this retrospective study, patients who underwent AKI-CRRT after cardiac surgery in our centre from January 2015 to January 2020 were included. Univariable and multivariable analyses were performed to identify the risk factors for in-hospital mortality.

Results
A total of 412 patients were included in our study. Of these, 174 died after AKI-CRRT, and the remaining 238 were included in the survival control group. Multivariable logistic regression analysis revealed that EuroSCORE > 7 (odds ratio [OR], 3.72; 95% confidence interval [CI], 1.92–7.24; p < 0.01), intraoperative bleeding > 1 L (OR, 2.14; 95% CI, 1.19–3.86; p = 0.01) and mechanical ventilation time > 70 h (OR, 5.03; 95% CI, 2.40–10.54; p < 0.01) were independent risk factors for in-hospital mortality in patients who had undergone AKI-CRRT. Our study also found that the use of furosemide after surgery was a protective factor for such patients (odds ratio, 0.48; 95% confidence interval, 0.25–0.92; p = 0.03).

Conclusions
In summary, the mortality of patients with AKI-CRRT after cardiac surgery remains high. The EuroSCORE, intraoperative bleeding and mechanical ventilation time were independent risk factors for in-hospital mortality. Continuous application of furosemide may be associated with a better outcome.
Hotspot mutation profiles of AKT1 in Asian women with breast and endometrial cancers
Authors: Shimoi Tatsunori , Hashimoto Jun , Sudo Kazuki , Shimomura Akihiko , Noguchi Emi , Shimizu Chikako , Yunokawa Mayu , Yonemori Kan , Yoshida Hiroshi , Yoshida Masayuki , Kato Tomoyasu , Kinoshita Takayuki , Fukuda Takahiro , Fujiwara Yasuhiro , Tamura Kenji 
Published: October 2021

Abstract
Background
The V-Akt murine thymoma viral oncogene (AKT) 1 (E17K) is a subfamily of serine/threonine protein kinases that affects the survival, proliferation, and invasion of cancer cells. The clinicopathological features and frequencies in Asian populations with AKT1 mutations in breast and endometrial cancers are unclear. Hence, we aimed to determine the frequencies and relationships between clinicopathological features and AKT1 mutations in Asian women with cancer.

Methods
We extracted DNA from 311 and 143 samples derived from patients with breast and endometrial cancers to detect the AKT1 point mutation (hotspot), E17K. We examined correlations between clinicopathological features and AKT1 mutation status.

Results
The frequency of AKT1 mutations in breast cancer was 7.4%, and they were found more frequently in human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtypes, although this was not statistically significant (P = 0.08). The frequency of AKT1 mutations in endometrial cancer was 4.1%, and the mutations were histologically detected only in endometrioid types. However, AKT1 mutations did not correlate with relapse-free or overall survival of patients with breast or endometrial cancer.

Conclusions
AKT1 mutations are associated with HER2-negative subtype in breast cancer and in endometrial cancer with endometrioid histology. The frequencies of AKT1 mutations in breast and endometrial cancers were similar between Asian and other regional women. The frequency of mutations is too low in both tumor types to talk about predictive significance.
Health risk behaviours among adolescents in Argentina: trends between 2007, 2012 and 2018 national cross-sectional school surveys
Authors: Peltzer Karl , Pengpid Supa 
Published: October 2021

Abstract
Background
The aim of this study was to assess trends of various health risk behaviours among adolescents across three different surveys in Argentina.

Methods
Data from 115,697 adolescents (mean age:14.6 years, SD=1.2) that participated in three cross-sectional national school surveys in 2007, 2012 and 2018 were analysed. In all, 27 health risk behaviours were assessed through a self-administered questionnaire. Significance of a linear trend was tested by treating study year as categorical variable in logistic regression analyses, adjusted by age group and food insecurity for boys and girls separately

Results
Among both sexes, four health risk behaviours (current cigarette use, passive smoking, trouble from alcohol use, and physically attacked) significantly reduced from 2007 to 2018. Among boys five health risk behaviours (experience of hunger, parental tobacco use, current alcohol use, involvement in physical fighting, and multiple sexual partners), and among girls, inadequate physical activity significantly reduced over time. Among both sexes, the prevalence of four health risk behaviours (overweight/obesity, obesity, leisure-time sedentary behaviour and insufficient fruit intake) significantly increased among both sexes, and among girls ten health risk behaviours (not walking/biking to school, current other tobacco use, bullying victimisation, lifetime drunkenness, having no close friends, suicide plan, suicidal ideation, worry-induced sleep disturbance, loneliness, and ever sexual intercourse) significantly increased over time.

Conclusion
Nine health risk behaviours among boys and five health risk behaviours among girls decreased, and four health risk behaviours among boys and 14 health compromising behaviours among girls increased over a period of 11 years. School health programmes for adolescents should be strengthened in Argentina.
Impact of COVID-19 on life expectancy at birth in India: a decomposition analysis
Authors: Yadav Suryakant , Yadav Pawan Kumar , Yadav Neha 
Published: October 2021

Abstract
Background
Quantifying excess deaths and their impact on life expectancy at birth (e0) provide a more comprehensive understanding of the burden of coronavirus disease of 2019 (COVID-19) on mortality. The study aims to comprehend the repercussions of the burden of COVID-19 disease on the life expectancy at birth and inequality in age at death in India.

Methods
The mortality schedule of COVID-19 disease in the pandemic year 2020 was considered one of the causes of death in the category of other infectious diseases in addition to other 21 causes of death in the non-pandemic year 2019 in the Global Burden of Disease (GBD) data. The measures e0 and Gini coefficient at age zero (G0) and then sex differences in e0 and G0 over time were analysed by assessing the age-specific contributions based on the application of decomposition analyses in the entire period of 2010–2020.

Results
The e0 for men and women decline from 69.5 and 72.0 years in 2019 to 67.5 and 69.8 years, respectively, in 2020. The e0 shows a drop of approximately 2.0 years in 2020 when compared to 2019. The sex differences in e0 and G0 are negatively skewed towards men. The trends in e0 and G0 value reveal that its value in 2020 is comparable to that in the early 2010s. The age group of 35–79 years showed a remarkable negative contribution to Δe0 and ΔG0. By causes of death, the COVID-19 disease has contributed − 1.5 and − 9.5%, respectively, whereas cardiovascular diseases contributed the largest value of was 44.6 and 45.9%, respectively, to sex differences in e0 and G0 in 2020. The outcomes reveal a significant impact of excess deaths caused by the COVID-19 disease on mortality patterns.

Conclusions
The COVID-19 pandemic has negative repercussions on e0 and G0 in the pandemic year 2020. It has severely affected the distribution of age at death in India, resulting in widening the sex differences in e0 and G0. The COVID-19 disease demonstrates its potential to cancel the gains of six to eight years in e0 and five years in G0 and has slowed the mortality transition in India.
Family-focused obesity prevention program implementation in urban versus rural communities: a case study
Authors: Flattum Colleen , Friend Sarah , Horning Melissa , Lindberg Rebecca , Beaudette Jennifer , Fulkerson Jayne A. 
Published: October 2021

Abstract
Purpose
Despite public health efforts to reduce childhood obesity, there remains an unequal distribution of obesity among rural and urban children, with higher rates in rural areas. However, few studies have compared differences in program delivery. This paper aims to describe differences between an urban and rural program delivery of a family-focused, community-based intervention program to prevent and reduce obesity among children.

Methods
This paper uses a case study format to provide a descriptive analysis of similar obesity prevention programs, designed by the same research team, implemented in Minnesota in different settings (i.e., an urban and rural setting) with significant community engagement in the adaptation process. The rural NU-HOME program is compared to HOME-Plus, an urban family-based obesity prevention program for school-aged children.

Results
Community engagement in the adaptation process of an urban program to a rural program confirmed some anticipated program content and delivery similarities while identifying key differences that were necessary for adaptation related to engagement with the community, recruitment and data collection, and intervention delivery.

Discussion
When adapting research-tested programs from urban to rural areas, it is important to identify the modifiable behavioral, social, and environmental factors associated with obesity to ensure the content of effective childhood obesity prevention programs is relevant. Customizing a program to meet the needs of the community may increase reach, engagement, and sustainability. In addition, long-term dissemination of a tailored program may significantly reduce childhood obesity in rural communities and be implemented in other rural settings nationally.
Associations between depressive symptoms, anxiety symptoms, their comorbidity and health-related quality of life: a large-scale cross-sectional study
Authors: Liao Wei , Luo Zhicheng , Dong Xiaokang , Wu Xueyan , Mei Yongxia , Cui Ningning , Kang Ning , Lan Yali , Liu Xiaotian , Huo Wenqian , Wang Fang , Wang Chongjian 
Published: October 2021

Abstract
Background
There were few studies exploring the associations between depressive symptoms, anxiety symptoms and health-related quality of life (HRQoL) in the general population, especially in resource limited area. The aims of this study were to assess the associations between depressive symptoms, anxiety symptoms, their comorbidity and HRQoL in rural area.

Methods
A total of 23,496 eligible participants from Henan rural cohort were included. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) were employed to assess depressive and anxiety symptoms, respectively. HRQoL was measured via European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L). Tobit regression and generalized linear model were utilized to explore the associations between depressive symptoms, anxiety symptoms, their comorbidity and HRQoL.

Results
A total of 1320 individuals were identified as depressive symptoms with a prevalence rate of 5.62%, while 1198 participants were classified as anxiety symptoms with a prevalence rate of 5.10%. After multiple adjustment, the regression coefficients (β) and 95% confidence interval (CI) of utility index for depressive and anxiety symptoms were − 0.166 (− 0.182, − 0.149) and − 0.132 (− 0.149, − 0.114), respectively. The β and 95% CI of VAS score for depressive and anxiety symptoms were − 7.65 (− 8.60, − 6.70) and − 5.79 (− 6.78, − 4.80), respectively. Additionally, the comorbidity was strongly associated with low utility index and VAS score. These findings were observed robustly in men and women.

Conclusion
Depressive symptoms, anxiety symptoms and their comorbidity were associated with low HRQoL in rural population, which needed further efforts on preventive and treatment interventions.

Clinical trial registration
The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015.