bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes
Authors: Oliver-Williams Clare , Stevens David , Payne Rupert A. , Wilkinson Ian B. , Smith Gordon C. S. , Wood Angela 
Published: January 2022

Abstract
Background
Hypertensive disorders of pregnancy are common pregnancy complications that are associated with greater cardiovascular disease risk for mothers. However, risk of cardiovascular disease subtypes associated with gestational hypertension or pre-eclampsia is unclear. The present study aims to compare the risk of cardiovascular disease outcomes for women with and without a history of gestational hypertension and pre-eclampsia using national hospital admissions data.

Methods
This was a retrospective cohort study of national medical records from all National Health Service hospitals in England. Women who had one or more singleton live births in England between 1997 and 2015 were included in the analysis. Risk of total cardiovascular disease and 19 pre-specified cardiovascular disease subtypes, including stroke, coronary heart disease, cardiomyopathy and peripheral arterial disease, was calculated separately for women with a history of gestational hypertension and pre-eclampsia compared to normotensive pregnancies.

Results
Amongst 2,359,386 first live births, there were 85,277 and 74,542 hospital admissions with a diagnosis of gestational hypertension and pre-eclampsia, respectively. During 18 years (16,309,386 person-years) of follow-up, the number and incidence of total CVD for normotensive women, women with prior gestational hypertension and women with prior pre-eclampsia were n = 8668, 57.1 (95% CI: 55.9–58.3) per 100,000 person-years; n = 521, 85.8 (78.6–93.5) per 100,000 person-years; and n = 518, 99.3 (90.9–108.2) per 100,000 person-years, respectively. Adjusted HRs (aHR) for total CVD were aHR (95% CI) = 1.45 (1.33–1.59) for women with prior gestational hypertension and aHR = 1.62 (1.48–1.78) for women with prior pre-eclampsia.
Gestational hypertension was strongly associated with dilated cardiomyopathy, aHR = 2.85 (1.67–4.86), and unstable angina, aHR = 1.92 (1.33–2.77). Pre-eclampsia was strongly associated with hypertrophic cardiomyopathy, aHR = 3.27 (1.49–7.19), and acute myocardial infarction, aHR = 2.46 (1.72–3.53). Associations were broadly homogenous across cardiovascular disease subtypes and increased with a greater number of affected pregnancies.

Conclusions
Women with either previous gestational hypertension or pre-eclampsia are at greater risk of a range of cardiovascular outcomes. These women may benefit from clinical risk assessment or early interventions to mitigate their greater risk of various cardiovascular outcomes.
Green tea-derived theabrownin induces cellular senescence and apoptosis of hepatocellular carcinoma through p53 signaling activation and bypassed JNK signaling suppression
Authors: Xu Jiaan , Xiao Xiujuan , Yan Bo , Yuan Qiang , Dong Xiaoqiao , Du Quan , Zhang Jin , Shan Letian , Ding Zhishan , Zhou Li , Efferth Thomas 
Published: January 2022

Abstract
Background
Theabrownin (TB) is a bioactive component of tea and has been reported to exert effects against many human cancers, but its efficacy and mechanism on hepatocellular carcinoma (HCC) with different p53 genotypes remains unclarified.

Methods
MTT assay, DAPI staining, flow cytometry and SA-β-gal staining were applied to evaluate the effects of TB on HCC cells. Quantitative real time PCR (qPCR) and Western blot (WB) were conducted to explore the molecular mechanism of TB. A xenograft model of zebrafish was established to evaluate the anti-tumor effect of TB.

Results
MTT assays showed that TB significantly inhibited the proliferation of SK-Hep-1, HepG2, and Huh7 cells in a dose-dependent manner, of which SK-Hep-1 was the most sensitive one with the lowest IC50 values. The animal data showed that TB remarkably suppressed SK-Hep-1 tumor growth in xenograft model of zebrafish. The cellular data showed TB's pro-apoptotic and pro-senescent effect on SK-Hep-1 cells. The molecular results revealed the mechanism of TB that p53 signaling pathway (p-ATM, p-ATR, γ-H2AX, p-Chk2, and p-p53) was activated with up-regulation of downstream senescent genes (P16, P21, IL-6 and IL-8) as well as apoptotic genes (Bim, Bax and PUMA) and proteins (Bax, c-Casp9 and c-PARP). The p53-mediated mechanism was verified by using p53-siRNA. Moreover, by using JNK-siRNA, we found JNK as a bypass regulator in TB's mechanism.

Conclusions
To sum up, TB exerted tumor-inhibitory, pro-senescent and pro-apoptotic effects on SK-Hep-1 cells through ATM-Chk2-p53 signaling axis in accompany with JNK bypass regulation. This is the first report on the pro-senescent effect and multi-target (p53 and JNK) mechanism of TB on HCC cells, providing new insights into the underlying mechanisms of TB's anti-HCC efficacy.
Psychometric analysis of the questionnaires for the assessment of upper limbs available in their Italian version: a systematic review of the structural and psychometric characteristics
Authors: Barni Luca , Ruiz-Muñoz María , Gonzalez-Sanchez Manuel , Cuesta-Vargas Antonio I. , Merchan-Baeza Jose , Freddolini Marco 
Published: January 2022

Abstract
Introduction
There is no systematic review that analyzes the psychometric properties of questionnaires in Italian. Previous studies have analyzed the psychometric characteristics of instruments for the measurement of pathologies of upper limbs and their joints in different languages. The aim of the present study was to analyze the psychometric properties of the questionnaires published in Italian for the evaluation of the entire upper limb or some of its specific regions and related dysfunctions.

Evidence acquisition
For the development of this systematic review, the following databases were used: PubMed, Scopus, Cochrane, Dialnet, Cinahl, Embase and PEDro. The selection criteria used in this study were: studies of transcultural adaptation to Italian of questionnaires oriented to the evaluation of upper limbs or any of their structures (specifically shoulder, elbow and wrist/hand), and contribution of psychometric variables of the questionnaire in its Italian version.

Evidence synthesis
After reading the titles and applying the inclusion and exclusion criteria to the complete documents, 16 documents were selected: 3 for the upper limb, 8 for the shoulder, 1 for the elbow and 4 for the wrist and hand. The cross-sectional psychometric variables show levels between good and excellent in all the questionnaires. Longitudinal psychometric variables had not been calculated in the vast majority of the analyzed questionnaires.

Conclusions
Italian versions of the questionnaires show good basic structural and psychometric characteristics for the evaluation of patients with musculoskeletal disorders of the upper limb and its joints (shoulder, elbow and wrist/hand).
Taste and chemical composition as drives for utilitarian redundancy and equivalence: a case study in local medical systems in Northeastern Brazil
Authors: Reinaldo Rafael Corrêa Prota dos Santos , Santoro Flávia Rosa , Albuquerque Ulysses Paulino , de Medeiros Patrícia Muniz 
Published: January 2022

Abstract
Background
We aimed to verify whether the taste and chemical composition influence the selection of plants in each medicinal category, whether within a socio-ecological system or between different socio-ecological systems. To this end, we use the theoretical bases of the Utilitarian Redundancy Model and the Utilitarian Equivalence Model. We studied the local medical systems of four rural communities in northeastern Brazil, used as models to test our assumptions.

Methods
The data on medicinal plants and local therapeutic function were obtained from semi-structured interviews associated with the free-listing method, allowing to generate indexes of similarity of therapeutic use between the plants cited in each region. During the interviews, each informer was also asked to report the tastes of the plants cited. Subsequently, we classified each plant in each region according to the most cited taste. The data about the chemical composition of each plant were obtained from a systematic review, using Web of Knowledge and Scopus databases.

Results
Pairs of plants with similar tastes are 1.46 times more likely to have the same therapeutic function within a local medical system (redundancy), but not between medical systems (equivalence). We also find that chemical compounds are not primarily responsible for utilitarian redundancy and equivalence. However, there was a tendency for alkaloids to be doubly present with greater expressiveness in pairs of equivalent plants.

Conclusions
The results indicate that each social group can create its means of using the organoleptic characteristics as clues to select new species as medicinal. Furthermore, this study corroborates the main prediction of the Utilitarian Equivalence Model, that people in different environments choose plants with traits in common for the same functions.
MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC)
Authors: Pavic M. , Niyazi M. , Wilke L. , Corradini S. , Vornhülz M. , Mansmann U. , Al Tawil A. , Fritsch R. , Hörner-Rieber J. , Debus J. , Guckenberger M. , Belka C. , Mayerle J. , Beyer G. 
Published: January 2022

Abstract
Background
Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial.

Methods
This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the “mean cumulative pain index” rated every 4 weeks until death or end of study using numeric rating scale.

Discussion
An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life.

Trial registration

German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213.
Red yeast rice ameliorates non-alcoholic fatty liver disease through inhibiting lipid synthesis and NF-κB/NLRP3 inflammasome-mediated hepatic inflammation in mice
Authors: Zou Jian , Yan Chunyan , Wan Jian-Bo 
Published: January 2022

Abstract
Background
Red yeast rice (RYR), a nutraceutical with a profound cholesterol-lowering effect, was found to attenuate non-alcoholic fatty liver disease (NAFLD) in mice. Despite monacolin K in RYR being a specific inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMCGR), the mechanisms underlying the protective effects of RYR against NAFLD are not fully elucidated.

Methods
Using a mouse model of high-fat diet (HFD) feeding and a cellular model of HepG2 cells challenged by lipopolysaccharide (LPS) and palmitic acid (PA), the possible molecular mechanisms were exploited in the aspects of NF-κB/NLRP3 inflammasome and mTORC1-SREBPs signaling pathways by examining the relevant gene/protein expressions. Subsequently, the correlation between these two signals was also verified using cellular experiments.

Results
RYR ameliorated lipid accumulation and hepatic inflammation in vivo and in vitro. RYR improved lipid metabolism through modulating mTORC1-SREBPs and their target genes related to triglyceride and cholesterol synthesis. Furthermore, RYR suppressed hepatic inflammation by inhibiting the NF-κB/NLRP3 inflammasome signaling. Interestingly, the treatment with RYR or MCC950, a specific NLRP3 inhibitor, resulted in the reduced lipid accumulation in HepG2 cells challenged by LPS plus PA, suggesting that the inhibitory effects of RYR on NLRP3 inflammasome-mediated hepatic inflammation may partially, in turn, contribute to the lipid-lowering effect of RYR.

Conclusions
The modulation of NF-κB/NLRP3 inflammasome and lipid synthesis may contribute to the ameliorative effects of RYR against HFD-induced NAFLD.
Lessons to be learned: identifying high-risk medication and circumstances in patients at risk for suicidal self-poisoning
Authors: Geith Stefanie , Didden Christiane , Rabe Christian , Zellner Tobias , Ott Armin , Eyer Florian 
Published: January 2022

Abstract
Background
Although the total number of suicides decreased since the beginning of the 1980s, the number of suicide-related behaviors using self-intoxication increased. Therefore, research on the characteristics of individuals committing self-intoxication becomes of growing importance for risk assessments and the development of preventive measures.

Methods
In this prospective, observational, monocentric cohort study, all incoming calls at our Poisons Control Centre reporting suicide-related behaviors through self-intoxication, were analyzed via a standardized questionnaire over 12 months. Both univariate and bivariate analyses were performed.

Results
1238 cases of deliberate intoxication were included in the study. The majority of cases occurred in the age group between 18 and 44 (n = 607/49%), two-thirds were female (n = 817/66%). The main substances used were antidepressants (n = 420/34%), peripheral analgesics (n = 322/26%) and neuroleptics (n = 282/23%). The majority of patients ingested substances from their prescribed medication (n = 640/82%) with the highest proportion in those aged over 64 years (n = 72/113; 91%, p < 0.001). Substance use was reported for the minority of patients (n = 175/23%). For 704 cases (79%), a psychiatric disorder was documented. Factors associated with recurrent suicide-related behaviors were an underlying psychiatric disorder (OR = 6.2; 95% CI 3.8–10.4), substance use (OR = 2.4; 95% CI 1.5–3.8), and ingestion of neuroleptics (OR = 2.1, 95% CI 1.4–3.0) or antidepressants (OR = 1.6; 95% CI 1.2–2.3).

Conclusion
This study might contribute to identifying individuals with an increased risk of suicide-related behaviors by deliberate intoxication and to developing preventive strategies for future suicide attempt(s).
Staffing and patient-related factors affecting inpatient falls in a psychiatric hospital: a 5-year retrospective matched case–control study
Authors: Seeherunwong Acharaporn , Thunyadee Chanya , Vanishakije Wipa , Thanabodee-tummajaree Pavinee 
Published: January 2022

Abstract
Background
The frequency and severity of falls of psychiatric inpatients in Thailand have not been previously reported. Also, the risk factors of falls have been numerous and complicated. This study aimed to investigate the staffing factors and patient-related factors that increase the likelihood of falls among psychiatric inpatients.

Methods
A five-year retrospective matched case–control study was conducted that selected cases of inpatients who fell and which were reported to the hospital risk management system. Subjects were compared to two control patients from the same hospital (1:2) by age (± 5 years), sex, and admission the same year. The total sample consisted of 240 patients. Univariate and multivariate conditional logistic regression was used to analyze the data.

Results
Of the eighty falls, 86.3% resulted in temporary harm and required intervention. The multivariate model showed that three patient-related factors were associated with increased inpatient falls: (1) having an acute psychotic condition (adjusted odds ratio (AOR) = 4.34; 95% CI 1.45, 13.05; p < 0.05), (2) polypharmacy with more than four types of medicines (AOR = 3.06; 95% CI 1.59, 5.88; p < 0.05), and (3) taking atypical psychiatric drugs (AOR = 2.74; 95% CI 1.35, 5.58; p < 0.05). Staffing for 26–50 patients in the wards was more protective for falls than with 25 or fewer patients (AOR = .17; 95% CI 0.04, 0.72; p < 0.05).

Conclusions
The risk factors found may help assess fall risk and manage the number of patients in psychiatric units. Drug dosage and drug interaction of antipsychotic drugs and cardiovascular agents with other medications and drug administration timing before falls are recommended for further investigation. Also, staff ratio per patient and the proportion of staff mix in psychiatric units need further study to establish adequate levels of surveillance to prevent inpatient falls.
KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway
Authors: Yin Lijuan , Li Qinlong , Mrdenovic Stefan , Chu Gina Chia-Yi , Wu Boyang Jason , Bu Hong , Duan Peng , Kim Jayoung , You Sungyong , Lewis Michael S. , Liang Gangning , Wang Ruoxiang , Zhau Haiyen E. , Chung Leland W. K. 
Published: January 2022

Abstract
Background
Keratins (KRTs) are intermediate filament proteins that interact with multiple regulatory proteins to initiate signaling cascades. Keratin 13 (KRT13) plays an important role in breast cancer progression and metastasis. The objective of this study is to elucidate the mechanism by which KRT13 promotes breast cancer growth and metastasis.

Methods
The function and mechanisms of KRT13 in breast cancer progression and metastasis were assessed by overexpression and knockdown followed by examination of altered behaviors in breast cancer cells and in xenograft tumor formation in mouse mammary fat pad. Human breast cancer specimens were examined by immunohistochemistry and multiplexed quantum dot labeling analysis to correlate KRT13 expression to breast cancer progression and metastasis.

Results
KRT13-overexpressing MCF7 cells displayed increased proliferation, invasion, migration and in vivo tumor growth and metastasis to bone and lung. Conversely, KRT13 knockdown inhibited the aggressive behaviors of HCC1954 cells. At the molecular level, KRT13 directly interacted with plakoglobin (PG, γ-catenin) to form complexes with desmoplakin (DSP). This complex interfered with PG expression and nuclear translocation and abrogated PG-mediated suppression of c-Myc expression, while the KRT13/PG/c-Myc signaling pathway increased epithelial to mesenchymal transition and stem cell-like phenotype. KRT13 expression in 58 human breast cancer tissues was up-regulated especially at the invasive front and in metastatic specimens (12/18) (p < 0.05). KRT13 up-regulation in primary breast cancer was associated with decreased overall patient survival.

Conclusions
This study reveals that KRT13 promotes breast cancer cell growth and metastasis via a plakoglobin/c-Myc pathway. Our findings reveal a potential novel pathway for therapeutic targeting of breast cancer progression and metastasis.
Pediatric Tuina in children with autism spectrum disorder: a study protocol for a randomized controlled trial
Authors: Feng Xiang , Jiang Quanrui , Zhang Yuxing , Li Tao , Wei Wei , Yu Jun , Li Wu , Li Jiangshan 
Published: January 2022

Abstract
Background
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by repetitive stereotypical behavior and communication deficits. Currently, it lacks a specific clinical treatment method. Pediatric Tuina is a recent therapy in traditional Chinese medicine (TCM) and has been used to treat children with ASD. Nonetheless, it remains uncommon given the lack of large-scale evidence-based medical studies. This study aims to compare the efficacy of Tuina and conventional treatment in children with ASD.

Methods
Eligible children will be randomly assigned to either the pediatric Tuina plus conventional treatment group or to the conventional treatment alone group based on a random table at a ratio of 1:1. The effectiveness of the Tuina intervention for ASD will be evaluated by a third-party organization. The pre- and post-intervention scores on the Childhood Autism Rating Scale comprised the primary outcome, whereas pre- and post-intervention scores on the Autism Treatment Evaluation Checklist were the secondary outcomes to assess improvement in symptoms. Baseline values of the participants will be determined at the time of registration. Outcomes will be evaluated after the 30th treatment session. The follow-up period will last for 6 months after treatment.

Discussion
This study will evaluate the effectiveness and safety of Tuina in the treatment of ASD. The results of this study could provide reliable evidence to improve the management of patients with ASD.

Trial registration
Chinese Clinical Trial Registry (CHICTR), ChiCTR2000040452. Registered on 28 November 2020.