bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of TGR5 protects blood brain barrier via the BRCA1/Sirt1 pathway after middle cerebral artery occlusion in rats
Authors: Liang Hui , Matei Nathanael , McBride Devin W. , Xu Yang , Tang Jiping , Luo Benyan , Zhang John H. 
Published: May 2020

Abstract
Background
The disruption of the blood–brain barrier (BBB) plays a critical event in the pathogenesis of ischemia stroke. TGR5 is recognized as a potential target for the treatment for neurologic disorders.

Methods
This study investigated the roles of TGR5 activation in attenuating BBB damage and underlying mechanisms after middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were subjected to model of MCAO and TGR5 agonist, INT777, was administered intranasally. Small interfering RNA (siRNA) for TGR5 and BRCA1 were administered through intracerebroventricular injection 48 h before MCAO. Infarct volumes, brain water content, BBB permeability, neurological scores, Western blot, immunofluorescence staining and co- immunoprecipitation were evaluated.

Results
Endogenous TGR5 and BRCA1 were upregulated in the injured hemisphere after MCAO and TGR5 expressed in endothelial cells. Treatment with INT777 alleviated brain water content and BBB permeability, reduced infarction volume and improved neurological scores at 24 h and 72 h after ischemia. INT777 administration increased BRCA1 and Sirt1 expression, as well as upregulated expressions of tight junction proteins. Ischemic damage induced interaction of TGR5 with BRCA1. TGR5 siRNA and BRCA1 siRNA significantly inhibited expressions of BRCA1 and Sirt1, aggravated BBB permeability and exacerbated stroke outcomes after MCAO. The protective effects of INT777 at 24 h after MCAO were also abolished by TGR5 siRNA or BRCA1 siRNA.

Conclusions
Our findings demonstrate that activating TGR5 could reduce BBB breakdown and improve neurological functions through BRCA1/Sirt1 signaling pathway after MCAO. TGR5 may serve as a potential new candidate to relieve brain injury after MCAO.
Effects of fish oil supplementation on glucose control and lipid levels among patients with type 2 diabetes mellitus: a Meta-analysis of randomized controlled trials
Authors: Gao Chao , Liu Yang , Gan Yong , Bao Wei , Peng Xiaolin , Xing Qingbin , Gao Huiyu , Lai Jianqiang , Liu Liegang , Wang Zhu , Yang Yuexin 
Published: May 2020

Abstract
Background
Previous studies have yielded inconsistent findings on the role of fish oil in type 2 diabetes mellitus (T2DM). We systematically summarized the available evidence from randomized controlled trials (RCT) and aimed to investigate the effects of fish oil supplementation on glucose control and lipid levels among patients with T2DM.

Methods
A comprehensive literature search was performed in electronic databases (PubMed, ProQuest, Cochrane Library, CNKI, VIP, and Wanfang) to identify all relevant RCTs which were published up to May 31st, 2019. We used Modified Jadad Score system to evaluate the quality of each included RCT. The pooled effects were estimated using random-effects model and presented as standardized mean differences with 95% confidence intervals.

Results
A total of 12 RCTs were included in this meta-analysis. There was no significant difference in glucose control outcomes comparing fish oil supplementation to placebo. The effect size of fasting plasma glucose (FPG) was 0.13 (95% CI: − 0.03 to 0.28, p > 0.05). No marked change was observed in fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and HOMA of insulin resistance (HOMA-IR) levels. Fish oil supplementation was associated with a decrease of triglyceride (TG) level by − 0.40 (95%CI: − 0.53 to − 0.28, p < 0.05), and an increase of high density lipoprotein (HDL) cholesterol level by 0.21 (95%CI: 0.05 to 0.37, p < 0.05). In subgroup analysis, HDL cholesterol level was higher among Asian and low-dose(< 2 g/d n-3 PUFA) subgroups compared to their counterparts (p < 0.05). TG level was lower in mid and long duration groups, along with an inconspicuous difference in short duration group.

Conclusions
This meta-analysis shows that among patients with T2DM, fish oil supplementation leads to a favorable blood lipids profile but does not improve glucose control.
Application of droplet digital PCR for the detection of vector copy number in clinical CAR/TCR T cell products
Authors: Lu Alex , Liu Hui , Shi Rongye , Cai Yihua , Ma Jinxia , Shao Lipei , Rong Victor , Gkitsas Nikolaos , Lei Hong , Highfill Steven L. , Panch Sandhya , Stroncek David F. , Jin Ping 
Published: May 2020

Abstract
Background
Genetically engineered T cells have become an important therapy for B-cell malignancies. Measuring the efficiency of vector integration into the T cell genome is important for assessing the potency and safety of these cancer immunotherapies.

Methods
A digital droplet polymerase chain reaction (ddPCR) assay was developed and evaluated for assessing the average number of lenti- and retroviral vectors integrated into Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR)-engineered T cells.

Results
The ddPCR assay consistently measured the concentration of an empty vector in solution and the average number of CAR and TCR vectors integrated into T cell populations. There was a linear relationship between the average vector copy number per cell measured by ddPCR and the proportion of cells transduced as measured by flow cytometry. Similar vector copy number measurements were obtained by different staff using the ddPCR assay, highlighting the assays reproducibility among technicians. Analysis of fresh and cryopreserved CAR T and TCR engineered T cells yielded similar results.

Conclusions
ddPCR is a robust tool for accurate quantitation of average vector copy number in CAR and TCR engineered T cells. The assay is also applicable to other types of genetically engineered cells including Natural Killer cells and hematopoietic stem cells.
Bibliometric analysis of peer-reviewed literature on climate change and human health with an emphasis on infectious diseases
Authors: Sweileh Waleed M. 
Published: May 2020

Abstract
Background
Assessing research activity is important for planning future protective and adaptive policies. The objective of the current study was to assess research activity on climate change and health with an emphasis on infectious diseases.

Method
A bibliometric method was applied using SciVerse Scopus. Documents on climate change and human health were called “health-related literature” while documents on climate change and infectious diseases were called “infection-related literature”. The study period was from 1980 to 2019.

Results
The search query found 4247 documents in the health-related literature and 1207 in the infection-related literature. The growth of publications showed a steep increase after 2007. There were four research themes in the health-related literature: (1) climate change and infectious diseases; (2) climate change, public health and food security; (3) heat waves, mortality, and non-communicable diseases; and (4) climate change, air pollution, allergy, and respiratory health. The most frequently encountered pathogens/infectious diseases in the infection-related literature were malaria and dengue. Documents in infection-related literature had a higher h-index than documents in the health-related literature. The top-cited documents in the health-related literature focused on food security, public health, and infectious diseases while those in infection-related literature focused on water-, vector-, and mosquito-borne diseases. The European region had the highest contribution in health-related literature (n = 1626; 38.3%) and infection-related literature (n = 497; 41.2%). The USA led with 1235 (29.1%) documents in health-related literature and 365 (30.2%) documents in infection-related literature. The Australian National University ranked first in the health-related literature while the London School of Hygiene & Tropical Medicine ranked first in the infection-related literature. International research collaboration was inadequate. Documents published in the Environmental Health Perspectives journal received the highest citations per document. A total of 1416 (33.3%) documents in the health-related literature were funded while 419 (34.7%) documents in the infection-related literature were funded.

Conclusion
Research on climate change and human health is on the rise with research on infection-related issues making a good share. International research collaboration should be funded and supported. Future research needs to focus on the impact of climate change on psychosocial, mental, innovations, policies, and preparedness of health systems.
Huanglian Jiedu Decoction ameliorates DSS-induced colitis in mice via the JAK2/STAT3 signalling pathway
Authors: Lu Zhuo , Xiong Wanna , Xiao Simeng , Lin Yilong , Yu Kai , Yue Guihua , Liu Qiaoming , Li Fang , Liang Jianqin 
Published: May 2020

Abstract
Background
Ulcerative colitis (UC) is an intestinal disease which was characterized by intestinal inflammation, mucosal injury and fibrosis. In this paper, the effect of Huanglian Jiedu Decoction (HJD), a well-known traditional Chinese medicine with significant anti-inflammatory effect, on dextran sulphate sodium (DSS)-induced UC in mice and inhibition of JAK2/STAT3 pathway were investigated.

Methods
BALB/c mice were randomly divided into 6 groups: HJD group (high, medium and low dose), USAN group, UC group, and control group. UC in mice were induced through free access to 3% DSS solution. After being treated with HJD for 8 days, all animals were sacrifice. Pathological examination of colonic specimen was performed by H&E staining. Cytokines (TNF-α, IL-6, and IL-1β) in colon were assayed by ELISA and immunofluorescence, MPO in colon and ATT in serum were detected by ELISA. Moreover, mice in HJD group and UC group were treated with AG490 to inhibit the expression of JAK2 protein, then the expression of JAK2 and STAT3 protein in colon was determined by western blotting and immunofluorescence staining. Furthermore, KI67 in colon was examined by immunohistochemistry, and apoptosis was detected by TUNEL staining, and collagen deposition was assayed by Masson staining after JAK2/STAT3 pathway in UC mice was inhibited by HJD.

Results
After mice being treated with HJD, the symptoms (weight loss and haematochezia) of UC were alleviated, and the contents of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and MPO in colon were significantly decreased. The expression of JAK2 and STAT3 protein was reduced after administration with HJD. After JAK2/STAT3 pathway being inhibited with HJD, the cell apoptosis, collagen deposition and immunoreactivity of macrophage in colon were significantly reduced, but the expression of Ki67 was markedly enhanced in both UC group and HJD group compare with control group.

Conclusions
HJD treatment can alleviate intestinal mucosal damage and has the protective effect on UC by downregulating JAK2 and STAT3 expression to reduce inflammation via JAK2/STAT3 pathway.
COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review
Authors: Kowalewski Mariusz , Fina Dario , Słomka Artur , Raffa Giuseppe Maria , Martucci Gennaro , Lo Coco Valeria , De Piero Maria Elena , Ranucci Marco , Suwalski Piotr , Lorusso Roberto 
Published: May 2020

AbstractInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza’s characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.
RRNPP-type quorum-sensing systems regulate solvent formation, sporulation and cell motility in Clostridium saccharoperbutylacetonicum
Authors: Feng Jun , Zong Wenming , Wang Pixiang , Zhang Zhong-Tian , Gu Yanyan , Dougherty Mark , Borovok Ilya , Wang Yi 
Published: May 2020

Abstract
Background
Clostridium saccharoperbutylacetonicum N1-4 (HMT) is a strictly anaerobic, spore-forming Gram-positive bacterium capable of hyper-butanol production through the well-known acetone–butanol–ethanol fermentation process. Recently, five putative RRNPP-type QSSs (here designated as QSS1 to QSS5) were predicted in this bacterial strain, each of which comprises a putative RRNPP-type regulator (QssR1 to QssR5) and a cognate signaling peptide precursor (QssP1 to QssP5). In addition, both proteins are encoded by the same operon. The functions of these multiple RRNPP-type QSSs are unknown.

Results
To elucidate the function of multiple RRNPP-type QSSs as related to cell metabolism and solvent production in N1-4 (HMT), we constructed qssR-deficient mutants ΔR1, ΔR2, ΔR3 and ΔR5 through gene deletion using CRISPR–Cas9 and N1-4-dcas9-R4 (with the QssR4 expression suppressed using CRISPR–dCas9). We also constructed complementation strains by overexpressing the corresponding regulator gene. Based on systematic characterization, results indicate that QSS1, QSS2, QSS3, and QSS5 positively regulate the sol operon expression and thus solvent production, but they likely negatively regulate cell motility. Consequently, QSS4 might not directly regulate solvent production, but positively affect cell migration. In addition, QSS3 and QSS5 appear to positively regulate sporulation efficiency.

Conclusions
Our study provides the first insights into the roles of multiple RRNPP-type QSSs of C. saccharoperbutylacetonicum for the regulation of solvent production, cell motility, and sporulation. Results of this study expand our knowledge of how multiple paralogous QSSs are involved in the regulation of essential bacterial metabolism pathways.
Comparison of device-based physical activity and sedentary behaviour following percutaneous coronary intervention in a cohort from Sweden and Australia: a harmonised, exploratory study
Authors: Freene Nicole , Borg Sabina , McManus Margaret , Mair Tarryn , Tan Ren , Davey Rachel , Öberg Birgitta , Bäck Maria 
Published: May 2020

Abstract
Background
Few studies have measured device-based physical activity and sedentary behaviour following a percutaneous coronary intervention (PCI), with no studies comparing these behaviours between countries using the same methods. The aim of the study was to compare device-based physical activity and sedentary behaviour, using a harmonised approach, following a PCI on-entry into centre-based cardiac rehabilitation in two countries.

Methods
A cross-sectional study was conducted at two outpatient cardiac rehabilitation centres in Australia and Sweden. Participants were adults following a PCI and commencing cardiac rehabilitation (Australia n = 50, Sweden n = 133). Prior to discharge from hospital, Australian participants received brief physical activity advice (< 5 mins), while Swedish participants received physical activity counselling for 30 min. A triaxial accelerometer (Actigraph GT3X/ActiSleep) was used to objectively assess physical activity (light (LPA), moderate-to-vigorous (MVPA)) and sedentary behaviour. Outcomes included daily minutes of physical activity and sedentary behaviour, and the proportion and distribution of time spent in each behaviour.

Results
There was no difference in age, gender or relationship status between countries. Swedish (S) participants commenced cardiac rehabilitation later than Australian (A) participants (days post-PCI A 16 vs S 22, p < 0.001). Proportionally, Swedish participants were significantly more physically active and less sedentary than Australian participants (LPA A 27% vs S 30%, p < 0.05; MVPA A 5% vs S 7%, p < 0.01; sedentary behaviour A 68% vs S 63%, p < 0.001). When adjusting for wear-time, Australian participants were doing less MVPA minutes (A 42 vs S 64, p < 0.001) and more sedentary behaviour minutes (A 573 vs S 571, p < 0.001) per day. Both Swedish and Australian participants spent a large part of the day sedentary, accumulating 9.5 h per day in sedentary behaviour.

Conclusion
Swedish PCI participants when commencing cardiac rehabilitation are more physically active than Australian participants. Potential explanatory factors are differences in post-PCI in-hospital physical activity education between countries and pre-existing physical activity levels. Despite this, sedentary behaviour is high in both countries. Internationally, interventions to address sedentary behaviour are indicated post-PCI, in both the acute setting and cardiac rehabilitation, in addition to traditional physical activity and cardiac rehabilitation recommendations.

Trial registrations
Australia: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12615000995572. Registered 22 September 2015, Sweden: World Health Organization Trial Registration Data Set: NCT02895451.
Periodized resistance training for persistent non-specific low back pain: a mixed methods feasibility study
Authors: Tjøsvoll Svein O. , Mork Paul J. , Iversen Vegard M. , Rise Marit B. , Fimland Marius S. 
Published: May 2020

Abstract
Background
We investigated the feasibility of a 16-week supervised heavy resistance training program with weekly undulating periodization for individuals with persistent non-specific low-back pain (LBP).

Methods
Twenty-five adults with persistent non-specific LBP participated in this mixed methods feasibility study. Participants trained a whole-body program consisting of squat, bench press, deadlift and pendlay row two times per week for 16 weeks. We assessed pain intensity, pain-related disability, pain self-efficacy and one-repetition maximum strength at baseline, 8 weeks and 16 weeks. Three focus group interviews were conducted at the end of the program. Linear mixed models were used to assess changes in outcomes, and the qualitative data was assessed using systematic text condensation.

Results
We observed clinically meaningful reductions in pain intensity after 8 and 16 weeks of training. The mean difference on the numeric pain rating scale (0–10) in the last 2 weeks from baseline to 8 weeks was 2.6 (95% CI: 1.8–3.6) and from baseline to 16 weeks 3.4 (95% CI: 2.5–4.4). In addition, there were improvements in pain-related disability (3.9, 95% CI: 2.3–5.5), pain self-efficacy (7.7, 95% CI: 5.4–10.1) and muscle strength. In the focus group interviews, participants talked about challenges regarding technique, the importance of supervision and the advantages of periodizing the training. Perceived benefits were improved pain, daily functioning, energy level and sleep, and changes in views on physical activity.

Conclusion
Periodized resistance training with weekly undulating periodization is a feasible training method for this group of individuals with persistent non-specific LBP. A randomized clinical trial should assess the efficacy of such an intervention.

Trial registration
clinicaltrials.gov/ Identifier – NCT04284982, Registered on February 24th 2020.
Systematic review of patient-oriented interventions to reduce unnecessary use of antibiotics for upper respiratory tract infections
Authors: Mortazhejri Sameh , Hong Patrick Jiho , Yu Ashley M. , Hong Brian Younho , Stacey Dawn , Bhatia R. Sacha , Grimshaw Jeremy M. 
Published: May 2020

AbstractBackgroundAntibiotics are prescribed frequently for upper respiratory tract infections (URTIs) even though most URTIs do not require antibiotics. This over-prescription contributes to antibiotic resistance which is a major health problem globally. As physicians’ prescribing behaviour is influenced by patients’ expectations, there may be some opportunities to reduce antibiotic prescribing using patient-oriented interventions. We aimed to identify these interventions and to understand which ones are more effective in reducing unnecessary use of antibiotics for URTIs.MethodsWe conducted a systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), CINAHL, and the Web of Science. We included English language randomized controlled trials (RCTs), quasi-RCTs, controlled before and after studies, and interrupted time series (ITS) studies. Two authors screened the abstract/titles and full texts, extracted data, and assessed study risk of bias. Where pooling was appropriate, a meta-analysis was performed by using a random-effects model. Where pooling of the data was not possible, a narrative synthesis of results was conducted.ResultsWe included 13 studies (one ITS, one cluster RCTs, and eleven RCTs). All interventions could be classified into two major categories: delayed prescriptions (seven studies) and patient/public information and education interventions (six studies). Our meta-analysis of delayed prescription studies observed significant reductions in the use of antibiotics for URTIs (OR = 0.09, CI 0.03 to 0.23; six studies). A subgroup analysis showed that prescriptions that were given at a later time and prescriptions that were given at the index consultation had similar effects. The studies in the patient/public information and education group varied according to their methods of delivery. Since only one or two studies were included for each method, we could not make a definite conclusion on their effectiveness. In general, booklets or pamphlets demonstrated promising effects on antibiotic prescription, if discussed by a practitioner.ConclusionsPatient-oriented interventions (especially delayed prescriptions) may be effective in reducing antibiotic prescription for URTIs. Further research is needed to investigate the costs and feasibility of implementing these interventions as part of routine clinical practice.Systematic review registrationPROSPEROCRD42016048007.
Adherence to drug therapy for hypertensive disorders of pregnancy: a cross-sectional survey
Authors: Chen Haihong , Tang Yuqing , Liu Chenxi , Liu Junjie , Wang Kang , Zhang Xinping 
Published: May 2020

Abstract
Background
Hypertensive disorders of pregnancy (HDPs) are a major contributor to maternal mortality worldwide, and drug therapy for HDPs is complicated and special. Clinical guidelines help physicians optimize the care for HDPs, but little is known about whether physicians adhere to drug therapy guidelins well, especially in China. This study aims to evaluate adherence to the drug therapy guidelines of the Chinese Obstetricians and Gynecologists Association (COGA) for HDPs and to explore the corresponding associations with recommendation evidence.

Methods
A cross-sectional design was executed for 306 women with HDPs hospitalized in a maternity ward of a tertiary hospital from August 2014 to July 2015 in Hubei, China. Adherence to the COGA guidelines was evaluated according to six items: the time of use and route of administration and dosage of antihypertensive drugs, MgSO4, and corticosteroids. Binary logistic regression was adopted to explore the associations between adherence to clinical decisions and recommendation evidence.

Results
The average adherence rate for drug therapy for HDPs was 48.22%. The adherence rate for the time of antihypertensive drug and corticosteroid use scored 95.65 and 86.75%, whereas the other four items of the time of MgSO4 use and the routes of administration and dosages of antihypertensive drugs, MgSO4, and corticosteroids scored < 50.00%. High- and low-evidence-based recommendations were followed in 40.00 and 54.70% of the decisions, respectively. Logistic regression revealed that recommendation evidence (OR = 0.588, P = 0.003) was associated with adherence.

Conclusions
Further improvement is still needed to achieve good adherence, especially regarding the time of MgSO4 use and drug dosage. High-evidence-based management of drug therapy for HDPs should be strengthened.