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The search strategy will be performed following the Peer Review of Electronic Search Strategies. The search strategy will be conducted in CINAHL, MEDLINE, Embase, PsycINFO, SciELO and Open Grey. Two review authors will independently appraise the full-text articles according to the COSMIN Risk of Bias checklist. Quality ratings and evidence synthesis will be performed using a modified Grading of Recommendations Assessment, Development and Evaluation approach.

Ethical approval is not necessary for systematic review protocols. The results will be disseminated by publication in a peer-reviewed journal and presented at a relevant conference.

CRD42020207586.

CRD42020207586.

To investigate the literature and determine if prematurity has an impact on long-term adverse kidney outcomes.

Systematic review.

OVID Medline, PubMed, SCOPUS, CINAHL and EMBASE databases were searched for studies relating to the adverse outcomes of prematurity from 1990 to April 2021.

All articles published between January 1990 and April 2021 that investigated whether premature infants developed long-term adverse renal outcomes were included in this review. learn more Articles must have been human studies and written in English. Case series with less than 20 participants and case studies were excluded.

One reviewer completed the database searches. Article selection was performed independently and in a non-blinded manner by both reviewers. Initial screening was by title and abstract. Full texts of remaining articles were reviewed. Articles for which inclusion was unclear were re-reviewed by both reviewers, and a unanimous decision was taken as to whether they should be included. The Newcastle-Ottawa Scale was . Premature birth conferred a twofold increased risk of CKD and extremely premature birth conferred a threefold increased risk of CKD. However, further larger multicentre studies are needed to draw definitive conclusions on the long-term kidney outcomes of prematurity.

Research has established that various forms of stigma (HIV stigma, gender non-conforming stigma and same-gender sex stigma) exist across Sub-Saharan Africa and have consequences for the utilisation of HIV prevention and care services. Stigmas are typically investigated in HIV literature individually or through investigating individual populations and the various stigmas they may face. The concept of intersectionality highlights the interconnected nature of social categorisations and their ability to create interdependent systems of discrimination based on gender, race, sexuality and so on. Drawing from perspectives on intersectionality, intersectional stigma denotes the convergence of multiple marginalised identities within an individual or a group, the experiences of stigma associated with these identities as well as the synergistic impact of these experiences on health and well-being. With respect to HIV, public health scholars can examine the impacts of intersectional stigmas on HIV prevention and care uate findings through peer-reviewed manuscripts, conferences and webinars.

Ethics approval is not required as there will be no human participants and no protected data will be used in this study. We will disseminate findings through peer-reviewed manuscripts, conferences and webinars.

Women living with HIV (WLWH) experience accelerated ageing and an increased risk of age-associated diseases earlier in life, compared with women without HIV. This is likely due to a combination of viral factors, gender differences, hormonal imbalance and psychosocial and structural conditions. This interdisciplinary cohort study aims to understand how biological, clinical and sociostructural determinants of health interact to modulate healthy ageing in WLWH.

The British Columbia

hildren and Women

nti

etroviral therapy and

arkers of

ging-

anadian

V

omen's Sexual and Reproductive Health Cohort

tudy (CARMA-CHIWOS) Collaboration (BCC3) study will enrol WLWH (n=350) and sociodemographically matched HIV-negative women (n=350) living in British Columbia. A subset of BCC3 participants will be past participants of CARMA, n≥1000 women and children living with and without HIV, 2008-2018 and/or CHIWOS, n=1422 WLWH, 2013-2018. Over two study visits, we will collect biological specimens for virus serolo knowledge translation. A Community Advisory Board will advise the research team throughout the study.

This study has been approved by the University of British Columbia Children's and Women's Research Ethics Board (H19-00896). Results will be shared in peer-reviewed journals, conferences and at community events as well as at www.hivhearme.ca and @HIV_HEAR_me. WLWH are involved in study design, survey creation, participant recruitment, data collection and knowledge translation. A Community Advisory Board will advise the research team throughout the study.

Hypertension and diabetes mellitus are important risk factors for cardiovascular diseases (CVDs). Once identified with these conditions, individuals need to be linked to primary healthcare system for initiation of lifestyle modifications, pharmacotherapy and maintenance of therapies to achieve optimal blood pressure and glycaemic control. In the current study, we evaluated predictors and barriers for non-linkage to primary-care public health facilities for CVD risk reduction.

We conducted a community-based longitudinal study in 16 urban slum clusters in central India. Community health workers (CHWs) in each urban slum cluster screened all adults, aged 30 years or more for hypertension and diabetes, and those positively screened were sought to be linked to urban primary health centres (UPHCs). We performed univariate and multivariate analysis to identify independent predictors for non-linkage to primary-care providers. We conducted in-depth assessment in 10% of all positively screened, to identify key barring linkages to primary-care facilities.

This study demonstrates feasibility of CHW-based strategy in promoting linkages to primary-care facilities.

Self-harm is the most common risk factor for suicide, and so those who present to hospital following self-harm provide an opportunity for targeted clinical care interventions. Observational studies evaluating such interventions may be useful in overcoming limitations of controlled trials, but study design, statistical analyses and outcomes used must be appropriate. This methodological systematic review will describe, categorise, synthesise and compare the methodological aspects of studies evaluating interventions and aspects of clinical management following hospital-presenting self-harm in both observational and experimental (ie, controlled trials or quasi-experimental studies) study designs.

Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocol guidelines were followed in drafting this protocol. Search terms were developed (related to self-harm, hospital presentation and evaluation studies) and adapted for MEDLINE, PsycINFO, EMBASE, CINAHL, Cochrane Central Register of Controlled Tr-reviewed journal. Findings will be used to inform future studies in the area of hospital-presenting self-harm. Ethical approval is not required for this review.

CRD42020208714.

CRD42020208714.Transforming growth factor-β (TGF-β) is pro-metastatic in advanced cancers and its biological activities are mainly mediated by the Smad family of proteins. Smad4 is the central signal transducer and transcription factor in the TGF-β pathway, yet the underlying mechanisms that govern transcriptional activities of Smad4 are not fully understood. Here, we show that AMBRA1, a member of the DDB1 and CUL4-associated factor (DCAF) family of proteins, serves as the substrate receptor for Smad4 in the CUL4-RING (CRL4) ubiquitin ligase complex. The CRL4-AMBRA1 ubiquitin ligase mediates non-proteolytic polyubiquitylation of Smad4 to enhance its transcriptional functions. Consequently, AMBRA1 potentiated TGF-β signaling and critically promoted TGF-β-induced epithelial-to-mesenchymal transition, migration, and invasion of breast cancer cells. Mouse models of breast cancer demonstrated that AMBRA1 promotes metastasis. Collectively, these results show that CRL4-AMBRA1 facilitates TGF-β-driven metastasis by increasing Smad4 polyubiquitylation, suggesting AMBRA1 may serve as a new therapeutic target in metastatic breast cancer.Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the "lipidome" in prostate tumors with matched benign tissues (n=21), independent unmatched tissues (n=47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n=43). Significant differences in lipid composition were detected and spatially visualized in tumors compared to matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This first characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting.Pseudogenes may play important roles in cancer. Here, we explore the mechanism and function of a pseudogene WTAPP1 in the progress of pancreatic ductal adenocarcinoma (PDAC). WTAPP1 RNA was significantly elevated in PDAC and was associated with poor prognosis in patients. Overexpression of WTAPP1 RNA promoted PDAC proliferation and invasiveness in vitro and in vivo. Mechanistically, N6-methyladenosine (m6A) modification stabilized WTAPP1 RNA via CCHC-type zinc finger nucleic acid binding protein (CNBP), resulting in increased levels of WTAPP1 RNA in PDAC cells. Excessive WTAPP1 RNA bound its protein-coding counterpart WT1 associated protein (WTAP) mRNA and recruited more EIF3 translation initiation complex to promote WTAP translation. Increased WTAP protein enhanced the activation of Wnt signaling and provoked the malignant phenotypes of PDAC. Decreasing WTAPP1 RNA significantly suppressed the in vivo growth and metastasis of PDAC cell lines and patient-derived xenografts. These results indicate that m6A-mediated increases in WTAPP1 expression promotes PDAC progression and thus may serve as a therapeutic target.Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score less then 3 (risk ratio (RR) 0.

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