bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guidelines and best practice recommendations on reproductive health services provision amid COVID-19 pandemic: scoping review
Authors: Tolu Lemi Belay , Feyissa Garumma Tolu , Jeldu Wondimu Gudu 
Published: February 2021

Abstract
Background
Policymakers and health professionals prefer to use summarized evidence of practice recommendations. The aim of this scoping review is therefore to identify available guidelines, consensus statements, the standard of practice, and practice recommendations on reproductive health service provision during the COVID-19 pandemics.

Methods
We searched guideline databases and websites of professional associations and international organizations working on sexual and reproductive health. We looked for practice recommendations on sexual reproductive health services (SRH) during COVID-19 pandemics. Additionally, we searched: MEDLINE, EMBASE, and Google Scholar. Data extraction was done by two independent reviewers using a customized tool that was developed to record the key information of the source that’s relevant to the review question. The difference between the two authors on data extraction was resolved by discussion.

Results
A total of 21 records were included in the review. Identified recommendations were classified into thematic areas. The records addressed approaches to antenatal care, labour and delivery, postnatal care, safe abortion, contraception, gender-based violence, and artificial reproduction.

Conclusions
There were consistent consensus statements and recommendations that there should be access to sexual and reproductive health services like antenatal care (ANC), postnatal care (PNC), contraception service, safe abortion care, and clinical management of rape survivors during the COVID-19 pandemics with the concerted effort of service re-organization. The practice recommendations focus on innovative ways of service provision to minimize patient and staff exposure to COVID-19 as well as alleviate the burden on the health care system. These include utilizing telemedicine and community/home-based care or self-care.
Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack
Authors: Ma Tian-Tian , Wong Ian C. K. , Whittlesea Cate , Man Kenneth K. C. , Lau Wallis , Wang Zixuan , Brauer Ruth , MacDonald Thomas M. , Mackenzie Isla S. , Wei Li 
Published: February 2021

Abstract
Background
To manage the risk factors and to improve clinical outcomes, patients with stroke commonly receive multiple cardiovascular medications. However, there is a lack of evidence on the optimum combination of medication therapy in the primary care setting after ischemic stroke. Therefore, this study aimed to investigate the effect of multiple cardiovascular medications on long-term survival after an incident stroke event (ischemic stroke or transient ischemic attack (TIA)).

Methods
This study consisted of 52,619 patients aged 45 and above with an incident stroke event between 2007 and 2016 in The Health Improvement Network database. We estimated the risk of all-cause mortality in patients with multiple cardiovascular medications versus monotherapy using a marginal structural model.

Results
During an average follow-up of 3.6 years, there were 9230 deaths (7635 in multiple cardiovascular medication groups and 1595 in the monotherapy group). Compared with patients prescribed monotherapy only, the HRs of mortality were 0.82 (95% CI 0.75–0.89) for two medications, 0.65 (0.59–0.70) for three medications, 0.61 (0.56–0.67) for four medications, 0.60 (0.54–0.66) for five medications and 0.66 (0.59–0.74) for ≥ six medications. Patients with any four classes of antiplatelet agents (APAs), lipid-regulating medications (LRMs), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, diuretics and calcium channel blockers (CCBs) had the lowest risk of mortality (HR 0.51, 95% CI 0.46–0.57) versus any one class. The combination containing APAs, LRMs, ACEIs/ARBs and CCBs was associated with a 61% (95% CI 53–68%) lower risk of mortality compared with APAs alone.

Conclusion
Our results suggested that combination therapy of four or five cardiovascular medications may be optimal to improve long-term survival after incident ischemic stroke or TIA. APAs, LRMs, ACEIs/ARBs and CCBs were the optimal constituents of combination therapy in the present study.
The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya
Authors:   LSHTM CMMID COVID-19 Working Group, Mburu C. N. , Ojal J. , Chebet R. , Akech D. , Karia B. , Tuju J. , Sigilai A. , Abbas K. , Jit M. , Funk S. , Smits G. , van Gageldonk P. G. M. , van der Klis F. R. M. , Tabu C. , Nokes D. J. , Scott JAG , Flasche S. , Adetifa IMO 
Published: February 2021

AbstractBackgroundThe COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.MethodsCombining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.ResultsIn February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8–54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19–54), 46% (30–59), and 54% (43–64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25–56), 54% (43–63), and 67% (59–72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives.ConclusionWhile contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.
Modifiable lifestyle factors and severe COVID-19 risk: a Mendelian randomisation study
Authors: Li Shuai , Hua Xinyang 
Published: February 2021

Abstract
Background
Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death. However, whether these relationships are causal is not well known; neither for the relationships between COVID-19 severe illness and other common lifestyle factors, such as physical activity and alcohol consumption.

Methods
Genome-wide significant genetic variants associated with body mass index (BMI), lifetime smoking, physical activity and alcohol consumption identified by large-scale genome-wide association studies (GWAS) of up to 941,280 individuals were selected as instrumental variables. Summary statistics of the genetic variants on severe illness of COVID-19 were obtained from GWAS analyses of up to 6492 cases and 1,012,809 controls. Two-sample Mendelian randomisation analyses were conducted.

Results
Both per-standard deviation (SD) increase in genetically predicted BMI and lifetime smoking were associated with about two-fold increased risks of severe respiratory COVID-19 and COVID-19 hospitalization (all P < 0.05). Per-SD increase in genetically predicted physical activity was associated with decreased risks of severe respiratory COVID-19 (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.05, 0.74; P = 0.02), but not with COVID-19 hospitalization (OR = 0.44; 95% CI 0.18, 1.07; P = 0.07). No evidence of association was found for genetically predicted alcohol consumption. Similar results were found across robust Mendelian randomisation methods.

Conclusions
Evidence is found that BMI and smoking causally increase and physical activity might causally decrease the risk of COVID-19 severe illness. This study highlights the importance of maintaining a healthy lifestyle in protecting from COVID-19 severe illness and its public health value in fighting against COVID-19 pandemic.
Temporarily switching from oral to intravenous selexipag in patients with pulmonary arterial hypertension: safety, tolerability, and pharmacokinetic results from an open-label, phase III study
Authors: Klose Hans , Chin Kelly M. , Ewert Ralf , Gall Henning , Parambil Joseph , Poch David , Seyfarth Hans-Jürgen , Axelsen Lene N. , Hsu Schmitz Shu-Fang , Stein Claudia , Preston Ioana R. 
Published: February 2021

Abstract
Background
The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov).

Methods
PAH patients receiving stable oral selexipag doses were enrolled. Following three consecutive IV selexipag infusions patients resumed oral selexipag. Corresponding IV and oral doses were selected to achieve comparable exposure to the active metabolite of selexipag. Safety outcomes were monitored throughout, and pharmacokinetic samples were obtained after oral and IV administration.

Results
All 20 patients completed the study. Fifteen patients had adverse events (AEs), most were mild, and none resulted in discontinuation. Headache was the most common AE throughout the study (four patients). Three serious AEs occurred in two patients with underlying comorbidities when oral dosing had resumed. There were no changes in WHO functional class for any patient and no clinically symptomatic changes in blood pressure were observed. Comparable exposure to the active metabolite of selexipag was demonstrated following corresponding oral and IV selexipag doses.

Conclusions
Temporarily switching between corresponding doses of oral and IV selexipag was well-tolerated with no unexpected safety findings and comparable exposure to the active metabolite. Treatment with IV selexipag is a feasible option to bridge temporary oral selexipag treatment interruptions.
Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach
Authors: Lezmi Guillaume , Vibhushan Shamila , Bevilaqua Claudia , Crapart Nicolas , Cagnard Nicolas , Khen-Dunlop Naziha , Boyle-Freyssaut Christine , Hadchouel Alice , Delacourt Christophe 
Published: February 2021

AbstractBackgroundThe pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood.AimThis study aimed to identify more precisely the molecular mechanisms limited to a compartment of lung tissue, through a transcriptomic analysis of the epithelium of macrocystic forms.MethodsTissue fragments displaying CCAM were obtained during planned surgical resections. Epithelial mRNA was obtained from cystic and normal areas after laser capture microdissection (LCM). Transcriptomic analyses were performed and the results were confirmed by RT-PCR and immunohistochemistry in independent samples.ResultsAfter controlling for RNA quality, we analysed the transcriptomes of six cystic areas and five control areas. In total, 393 transcripts were differentially expressed in the epithelium, between CCAM and control areas. The most highly redundant genes involved in biological functions and signalling pathways differentially expressed between CCAM and control epithelium includedTGFB2, TGFBR1, andMAP 2 K1. These genes were considered particularly relevant as they have been implicated in branching morphogenesis. RT-qPCR analysis confirmed in independent samples thatTGFBR1was more strongly expressed in CCAM than in control tissues (p < 0.03). Immunohistochemistry analysis showed TGFBR1 (p = 0.0007) and TGFB2 (p < 0.02) levels to be significantly higher in the epithelium of CCAM than in that of control tissues.ConclusionsThis compartmentalised transcriptomic analysis of the epithelium of macrocystic lung malformations identified a dysregulation of TGFB signalling at the mRNA and protein levels, suggesting a possible role of this pathway in CCAM pathogenesis.Trial registrationClinicalTrials.gov Identifier:NCT01732185.
LINC00963 affects the development of colorectal cancer via MiR-532-3p/HMGA2 axis
Authors: Ye Jinjun , Liu Jidong , Tang Tao , Xin Le , Bao Xing , Yan Yukuang 
Published: February 2021

Abstract
Background
LINC00963 is high-expressed in various carcinomas, but its expression and function in colorectal cancer (CRC) have not been explored. This study explored the role and mechanism of LINC00963 in CRC.

Methods
The expression of LINC00963 in CRC and its relationship with prognosis were examined by starBase and survival analysis. The effects of LINC00963, miR-532-3p and HMGA2 on the biological characteristics and EMT-related genes of CRC cells were studied by RT-qPCR, CCK-8, clone formation experiments, flow cytometry, scratch test, Transwell, and Western blot. Xenograft assay and immunohistochemistry were performed to verify the effect of LINC00963 on tumor growth. The correlation among LINC00963, miR-532-3p, and HMGA2 was analyzed by bioinformatics analysis, luciferase assay, and Pearson test.

Results
LINC00963 was high-expressed in CRC, and this was associated with poor prognosis of CRC. Silencing LINC00963 inhibited the activity, proliferation, migration, and invasion of CRC cells, MMP-3 and MMP-9 expressions, moreover, it also blocked cell cycle progression, and inhibited tumor growth and Ki67 expression. However, overexpression of LINC00963 showed the opposite effects to silencing LINC00963. LINC00963 targeted miR-532-3p to regulate HMGA2 expression. Down-regulation of miR-532-3p promoted cell proliferation, migration and invasion, and expressions of MMP-3 and MMP-9, and knockdown of HMGA2 reversed the effect of miR-532-3p inhibitor. Up-regulation of miR-532-3p inhibited the biological functions of CRC cells, and overexpression of HMGA2 reversed the miR-532-3p mimic effect.

Conclusion
LINC00963 affects the development of CRC through the miR-532-3p/HMGA2 axis.
circ-ANXA7 facilitates lung adenocarcinoma progression via miR-331/LAD1 axis
Authors: Wang Yu 
Published: February 2021

Abstract
Background
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, with a poor prognosis. The roles of circular RNAs (circRNAs) in tumors have been initially clarified. In this study, we probed into the functions and underlying molecular mechanisms of circ-ANXA7 in LUAD.

Methods
According to circRNA microarray analysis based on 40 pairs of LUAD tissues and non-tumor tissues, a novel circ-ANXA7 was up-regulated in LUAD, which was verified in LUAD tissues and cells by RT-qPCR. Correlation between its expression and clinical features of LUAD was analyzed. When transfected with sh-circ-ANXA7, proliferation, invasion, and migration of LUAD cells were determined by a series of functional assays. Furthermore, tumor growth was investigated in nude mice injected with sh-circ-ANXA7. Dual luciferase report and gain and loss assays were used to confirm the relationships between circ-ANXA7 and miR-331, miR-331 and LAD1.

Results
circ-ANXA7 was up-regulated in LUAD tissues and cells. Its high expression promoted proliferation, migration, and invasion of LUAD cells as well as tumor growth. High circ-ANXA7 expression usually predicted a poorer prognosis for LUAD patients. Furthermore, circ-ANXA7 could accelerate proliferation and invasion of LUAD cells by targeting miR-331. miR-331 directly bound to the 3′-UTR of LAD1. LAD1 induced proliferation and invasion of LUAD cells, which was reversed after co-transfection with circ-ANXA7 knockdown. LAD1 expression could be an independent prognostic marker for LUAD by univariate and multivariate analysis.

Conclusions
Our research identified a novel circ-ANXA7 for LUAD, which could facilitate proliferation, migration, and invasion of LUAD cells by miR-331/ LAD1 axis. circ-ANXA7 could become a promising prognosis and treatment target for LUAD.
Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer
Authors: Long Fei , Lin Zhi , Li Liang , Ma Min , Lu Zhixing , Jing Liang , Li Xiaorong , Lin Changwei 
Published: February 2021

AbstractColorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.
2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy
Authors: Zhao Jiayan , Wu Hang , Zhao Jiulong , Yin Yichen , Zhang Zhilun , Wang Shige , Lin Kun 
Published: February 2021

AbstractOwing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg–Mn–Al layered double hydroxides (LDH) clay with MoS2doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2and imaging and catalytic functions of Mg–Mn–Al LDH. The designed LDH-MoS2(LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg–Mn–Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.
Peer driven or driven peers? A rapid review of peer involvement of people who use drugs in HIV and harm reduction services in low- and middle-income countries
Authors: Chang Judy , Shelly Shaun , Busz Machteld , Stoicescu Claudia , Iryawan Arif Rachman , Madybaeva Dinara , de Boer Yuri , Guise Andy 
Published: February 2021

Abstract
Introduction
Peer involvement of people who use drugs within HIV and harm reduction services is widely promoted yet under-utilised. Alongside political and financial barriers is a limited understanding of the roles, impacts, contexts and mechanisms for peer involvement, particularly in low- and middle-income settings. We conducted a rapid review of available literature on this topic.

Methods
Within a community-academic partnership, we used a rapid review approach, framed by realist theory. We used a network search strategy, focused on core journals and reference lists of related reviews. Twenty-nine studies were included. We developed thematic summaries framed by a realist approach of exploring interventions, their mechanisms, outcomes and how they are shaped by contexts.

Results
Reported outcomes of peer involvement included reduced HIV incidence and prevalence; increased service access, acceptability and quality; changed risk behaviours; and reduced stigma and discrimination. Mechanisms via which these roles work were trust, personal commitment and empathy, using community knowledge and experience, as well as ‘bridge’ and ‘role model’ processes. Contexts of criminalisation, under-resourced health systems, and stigma and discrimination were found to shape these roles, their mechanisms and outcomes. Though contexts and mechanisms are little explored within the literature, we identified a common theme across contexts, mechanisms and outcomes. Peer outreach interventions work through trust, community knowledge and expertise, and ‘bridge’ mechanisms (M) to counter criminalisation and constraining clinic and service delivery environments (C), contributing towards changed drug-using behaviours, increased access, acceptability and quality of harm reduction services and decreased stigma and discrimination (O).

Conclusion
Peer involvement in HIV and harm reduction services in low- and middle-income settings is linked to positive health outcomes, shaped by contexts of criminalisation, stigma, and resource scarcity. However, peer involvement is under-theorised, particularly on how contexts shape mechanisms and ultimately outcomes. Efforts to study peer involvement need to develop theory and methods to evaluate the complex mechanisms and contexts that have influence. Finally, there is a need to expand the range of peer roles, to embrace the capacities and expertise of people who use drugs.