bluuebunny/crossref_metadata_2025 huggingface dataset:
circ_0061265 competitively binds to microRNA-885-3p to promote the development of gastric cancer by upregulating AURKA expression
Authors: Fei Qian , Lin Yuhe , Zhang Mi , Guo Jinshuai , Liang Yuan
Published: September 2022

Background

Circular RNAs (circRNAs) represent a class of newly identified transcripts that act as competing endogenous RNAs (ceRNAs) to modulate gene expression by competing for the shared microRNAs (miRNAs) in humans. In this study, we set out to investigate the role of the circRNA-miRNA-mRNA ceRNA network in gastric cancer (GC).

Methods

A differential analysis on GC-related circRNAs, miRNAs and mRNAs was performed utilizing the R language “limma” package, followed by GO and KEGG enrichment analyses. The Cytoscape visualization software was used to construct the circRNA-miRNA-mRNA ceRNA network. RT-qPCR, Western blot assay, immunohistochemistry, RNA pull down, RIP and dual luciferase gene reporter assay were conducted to verify the expression of the related circRNA, miRNA and mRNA and their interaction in GC tissues and cells.

Results

The bioinformatics analysis screened 13 circRNAs, 241 miRNAs and 7483 mRNAs related to GC. Ten DEmRNAs (AURKA, BUB1, CCNF, FEN1, FGF2, ITPKB, CDKN1A, TRIP13, KNTC1 and KIT) were identified from the constructed PPI network and module analysis, among which AURKA was the most critical. A circ_0061265-miRNA-885-3p-AURKA ceRNA network was constructed. In vitro cell experiment demonstrated significantly upregulated circ_0061265 and AURKA, but downregulated miR-885-3p in GC. Moreover, circ_0061265 promoted the occurrence of GC by competitively binding to miRNA-885-3p to regulate AURKA expression.

Conclusion

Our work validated that circ_0061265 may increase AURKA expression by competitively binding to miRNA-885-3p, thereby promoting GC development.
Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer
Authors: Lei Kunjian , Luo Min , Tu Zewei , Lv Shigang , Liu Junzhe , Gong Chuandong , Ye Minhua , Wu Miaojing , Sheng Yilei , Long Xiaoyan , Li Jingying , Zhu Xingen , Huang Kai
Published: September 2022

Background

The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored.

Methods

We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx).

Results

Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells.

Conclusions

Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.
Prostate cancer in omics era
Authors: Gholami Nasrin , Haghparast Amin , Alipourfard Iraj , Nazari Majid
Published: September 2022

Recent advances in omics technology have prompted extraordinary attempts to define the molecular changes underlying the onset and progression of a variety of complex human diseases, including cancer. Since the advent of sequencing technology, cancer biology has become increasingly reliant on the generation and integration of data generated at these levels. The availability of multi-omic data has transformed medicine and biology by enabling integrated systems-level approaches. Multivariate signatures are expected to play a role in cancer detection, screening, patient classification, assessment of treatment response, and biomarker identification. This review reports current findings and highlights a number of studies that are both novel and groundbreaking in their application of multi Omics to prostate cancer.
Challenges to the right to health in sub-Saharan Africa: reflections on inequities in access to dialysis for patients with end-stage kidney failure
Authors: Ashu James Tataw , Mwangi Jackline , Subramani Supriya , Kaseje Daniel , Ashuntantang Gloria , Luyckx Valerie A.
Published: September 2022

Realization of the individual’s right to health in settings such as sub-Saharan Africa, where health care adequate resources are lacking, is challenging. This paper demonstrates this challenge by illustrating the example of dialysis, which is an expensive but life-saving treatment for people with kidney failure. Dialysis resources, if available in sub-Saharan Africa, are generally limited but in high demand, and clinicians at the bedside are faced with deciding who lives and who dies. When resource limitations exist, transparent and objective priority setting regarding access to such expensive care is required to improve equity across all health needs in a population. This process however, which weighs individual and population health needs, denies some the right to health by limiting access to health care.

This paper unpacks what it means to recognize the right to health in sub-Saharan Africa, acknowledging the current resource availability and scarcity, and the larger socio-economic context. We argue, the first order of the right to health, which should always be realized, includes protection of health, i.e. prevention of disease through public health and health-in-all policy approaches. The second order right to health care would include provision of universal health coverage to all, such that risk factors and diseases can be effectively and equitably detected and treated early, to prevent disease progression or development of complications, and ultimately reduce the demand for expensive care. The third order right to health care would include equitable access to expensive care. In this paper, we argue that recognition of the inequities in realization of the right to health between individuals with “expensive” needs versus those with more affordable needs, countries must determine if, how, and when they will begin to provide such expensive care, so as to minimize these inequities as rapidly as possible. Such a process requires good governance, multi-stakeholder engagement, transparency, communication and a commitment to progress. We conclude the paper by emphasizing that striving towards the progressive realization of the right to health for all people living in SSA is key to achieving equity in access to quality health care and equitable opportunities for each individual to maximize their own state of health.
Migrants in Swedish sexual and reproductive health and rights related policies: a critical discourse analysis
Authors: Amroussia Nada , Holmström Charlotta , Ouis Pernilla
Published: September 2022

Background

Previous research has shown that migrants in Sweden are disadvantaged in terms of sexual and reproductive health and rights (SRHR). SRHR policies might play a crucial role in shaping migrants’ SRHR outcomes. The purpose of the study was to critically examine: a) how migrants were represented in the discourses embedded within Swedish SRHR-related policies, and b) how migrants’ SRHR-related issues were framed and addressed within these discourses.

Methods

Critical discourse analysis (CDA) was used to analyze a total of 54 policy documents. Following Jäger’s approach to CDA, discourse strands and entanglements between different discourse strands were examined.

Results

Our findings consisted of three discourse strands: 1) “Emphasizing vulnerability”, 2) “Constructing otherness”, and 3) “Prioritizing the structural level or the individual level?”.

Migrants’ representation in Swedish SRHR-related policies is often associated with the concept of vulnerability, a concept that can hold negative connotations such as reinforcing social control, stigma, and disempowerment. Alongside the discourse of vulnerability, the discourse of otherness appears when framing migrants’ SRHR in relation to what is defined as honor-related violence and oppression. Furthermore, migrant SRHR issues are occasionally conceptualized as structural issues, as suggested by the human rights-based approach embraced by Swedish SRHR-related policies. Relevant structural factors, namely migration laws and regulations, are omitted when addressing, for example, human trafficking and HIV/AIDS.

Conclusions

We conclude that the dominant discourses favor depictions of migrants as vulnerable and as the Other. Moreover, despite the prevailing human rights-based discourse, structural factors are not always considered when framing and addressing migrants’ SRHR issues. This paper calls for a critical analysis of the concept of vulnerability in relation to migrants’ SRHR. It also highlights the importance of avoiding othering and paying attention to the structural factors when addressing migrants’ SRHR.
Diagnosis of pathogens causing bacterial meningitis using Nanopore sequencing in a resource-limited setting
Authors: Pallerla Srinivas Reddy , Van Dong Do , Linh Le Thi Kieu , Van Son Trinh , Quyen Dao Thanh , Hoan Phan Quoc , Trung Ngo Tat , The Nguyen Trong , Rüter Jule , Boutin Sébastien , Nurjadi Dennis , Sy Bui Tien , Kremsner Peter G. , Meyer Christian G. , Song Le Huu , Velavan Thirumalaisamy P.
Published: September 2022

Aim

The aim of the present study is to compare the performance of 16S rRNA Nanopore sequencing and conventional culture in detecting infectious pathogens in patients with suspected meningitis in a resource-limited setting without extensive bioinformatics expertise.

Methods

DNA was isolated from the cerebrospinal fluid (CSF) of 30 patients with suspected bacterial meningitis. The isolated DNA was subjected to 16S sequencing using MinION™. The data were analysed in real time via the EPI2ME cloud platform. The Nanopore sequencing was done in parallel to routine microbiological diagnostics.

Results

Nanopore sequencing detected bacterial pathogens to species level in 13 of 30 (43%) samples. CSF culture showed 40% (12/30) positivity. In 21 of 30 patients (70%) with suspected bacterial meningitis, both methods yielded concordant results. About nine of 30 samples showed discordant results, of these five were false positive and four were false negative. In five of the culture negative results, nanopore sequencing was able to detect pathogen genome, due to the higher sensitivity of the molecular diagnostics. In two other samples, the CSF culture revealed Cryptococcus neoformans and Streptococcus pneumoniae, which were not detected by Nanopore sequencing. Overall, using both the cultures and 16S Nanopore sequencing, positivity rate increased from 40% (12/30) to 57% (17/30).

Conclusion

Next-generation sequencing could detect pathogens within six hours and could become an important tool for both pathogen screening and surveillance in low- and middle-income countries (LMICs) that do not have direct access to extensive bioinformatics expertise.
Immunomolecular assay based on selective virion capture by spike antibody and viral nucleic acid amplification for detecting intact SARS-CoV-2 particles
Authors: Wu Xiaoli , Liu Junye , Zhang Hongpeng , Zhou Hua , Wang Wen , Ma Yuanyan , Shen Shimei , Cai Xuefei , Huang Ailong , Wang Deqiang
Published: September 2022

Background

Effective therapeutics and vaccines for coronavirus disease 2019 (COVID-19) are currently lacking because of the mutation and immune escape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the propagation characteristics of SARS-CoV-2, rapid and accurate detection of complete virions from clinical samples and the environment is critical for assessing infection risk and containing further COVID-19 outbreaks. However, currently applicable methods cannot achieve large-scale clinical application due to factors such as the high viral load, cumbersome virus isolation steps, demanding environmental conditions, and long experimental periods. In this study, we developed an immuno molecular detection method combining capture of the viral spike glycoprotein with monoclonal antibodies and nucleic acid amplification via quantitative reverse transcription PCR to rapidly and accurately detect complete virions.

Results

After constructing a novel pseudovirus, screening for specific antibodies, and optimizing the detection parameters, the assay achieved a limit of detection of 9 × 102 transduction units/mL of viral titer with high confidence (~ 95%) and excellent stability against human serum and common virus/pseudovirus. The coefficients of variation were 1.0 ~ 2.0% for intra-assay and inter-assay analyses, respectively. Compared with reverse transcription-PCR, the immunomolecular method more accurately quantified complete virions. SARS-CoV-2/pseudovirus was more stable on plastic and paper compared with aluminum and copper in the detection of SARS-CoV-2 pseudovirus under different conditions. Complete virions were detected up to 96 h after they were applied to these surfaces (except for copper), although the titer of the virions was greatly reduced.

Conclusion

Convenient, inexpensive, and accurate complete virus detection can be applied to many fields, including monitoring the infectivity of convalescent and post-discharge patients and assessing high-risk environments (isolation rooms, operating rooms, patient living environments, and cold chain logistics). This method can also be used to detect intact virions, including Hepatitis B and C viruses, human immunodeficiency virus, influenza, and the partial pulmonary virus, which may further improve the accuracy of diagnoses and facilitate individualized and precise treatments.

Graphical Abstract
Protection of zero-valent iron nanoparticles against sepsis and septic heart failure
Authors: Wang Daquan , Wang Changyu , Liang Zhenxing , Lei Wangrui , Deng Chao , Liu Xiaoli , Jiang Shuai , Zhu Yanli , Zhang Shaofei , Yang Wenwen , Chen Ying , Qiu Yao , Meng Lingjie , Yang Yang
Published: September 2022

Background

Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown.

Results

NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis.

Conclusions

The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.

Graphical Abstract
Engineering cancer cell membrane-camouflaged metal complex for efficient targeting therapy of breast cancer
Authors: Li Xiaoying , Yu Yanzi , Chen Qi , Lin Jiabao , Zhu Xueqiong , Liu Xiaoting , He Lizhen , Chen Tianfeng , He Weiling
Published: September 2022

Background

Cancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility.

Results

Therefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo.

Conclusion

In brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects.
Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability
Authors: Wang Yi , Wang Wenchao , Yu Endian , Zhuang Wenya , Sun Xuanrong , Wang Hong , Li Qingyong
Published: September 2022

Background

7-p-trifluoromethylphenyl-FL118 (FLQY2) is a camptothecin analog with excellent antitumor efficacy against various solid tumors. However, its poor solubility and low bioavailability limited the development of the drug. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), an emerging carrier for preparing solid dispersion (SD), encapsulated FLQY2 to circumvent the above limitations.

Results

In this project, FLQY2-SD was prepared by solvent evaporation method and self-assembled into micelles in aqueous solutions owing to the amphiphilic nature of Soluplus®. The physicochemical characterizations demonstrated that FLQY2 existed in a homogeneous amorphous form in SD and was rapidly dissolved. The micelles did not affect cytotoxicity or cellular uptake of FLQY2 in vitro, and the oral bioavailability was increased by 12.3-fold compared to the FLQY2 cyclodextrin suspension. The pharmacokinetics of FLQY2-SD showed rapid absorption, accumulation in the intestine, and slow elimination via fecal. Metabolite identification studies showed 14 novel metabolites were identified, including 12 phase I metabolites (M1–M12) and 2 phase II metabolites (M13–M14), of which M2 (oxidation after decarboxylation) and M7 (dioxolane ring cleavage) were the primary metabolites in the positive mode and negative mode, respectively. The tumor growth inhibition rate (TGI, 81.1%) of FLQY2-SD (1.5 mpk, p.o./QW) in tumor-bearing mice after oral administration was higher than that of albumin-bound Paclitaxel (15 mpk, i.v./Q4D) and Irinotecan hydrochloride (100 mpk, i.p./QW).

Conclusions

The successful preparation, pharmacokinetics, and pharmacodynamics studies of FLQY2-SD showed that the solubility and bioavailability of FLQY2 were improved, which facilitated the further druggability development of FLQY2.

Graphical Abstract
The effect of a pay-for-performance program on health-related quality of life for patients with hepatitis in Taiwan
Authors: Su Wei-Chih , Chen Tsung-Tai , Yang Sien-Sing , Shih Ling-Na , Liu Chih-Kuang , Wang Chia-Chi , Wu Chien-Hsien
Published: September 2022

Purpose

Chronic viral hepatitis is a major global public health problem. The guidelines suggest the long-term performance of regular ongoing liver examinations to monitor liver inflammation and screen for hepatocellular carcinoma. However, the effects of regular liver examinations on health-related quality of life (HRQoL) have not been adequately evaluated. Therefore, this study evaluated the effects of regular ongoing examinations on the quality of life of patients with hepatitis.

Methods

A cross-sectional study was conducted from October to December 2016 in four hospitals in northern Taiwan. A hepatitis pay-for-performance (P4P) program was launched in 2010 to ensure that hepatitis patients have regular ongoing liver examinations. The study group consisted of patients who joined and stayed in the program for more than one year. The study assessed HRQoL utilizing the five-level version of the EuroQol-5 Dimension (EQ-5D-5L) and the EuroQoL visual analog scale (EQ-VAS). The responses for the EQ-5D-5L in hepatitis patients were transformed into the EQ-5D index according to the Taiwanese population’s value set. Sociodemographic and clinical characteristics were collected by questionnaire, and descriptive statistics were presented. A two-part model and generalized linear model with a Poisson distribution and a log link function, respectively, were used to examine the associations of the EQ-5D index and EQ-VAS score with participation in the hepatitis P4P program. We applied propensity score weighting with inverse probability weighting to control for selection bias.

Results

In all, 508 patients (aged 57.6 ± 11.6 years; 60.8% male) were enrolled in this study. The mean (standard deviation, SD) reported EQ-5D index and EQ-VAS scores were 0.93 (0.12) and 75.1 (13.8), and the median (interquartile range, IQR) values were 1 (0.108) and 80 (15), respectively. The study group had a moderately significantly higher EQ-VAS score (mean ratio = 1.029, P < 0.001). However, the differences in the EQ-5D index scores between the study and control groups were not significant.

Conclusion

Patients with hepatitis partially benefited from receiving hepatitis P4P in Taiwan, which featured regular ongoing liver examinations, in that their EQ-VAS scores were enhanced but not their EQ-5D index scores.
The ICU-venous thromboembolism score and tumor grade can predict inhospital venous thromboembolism occurrence in critical patients with tumors
Authors: Mei Ruqi , Wang Guodong , Chen Renxiong , Wang Hongzhi
Published: September 2022

Background

Venous thromboembolism (VTE) is a threat to the prognosis of tumor patients, especially for critically ill patients. No uniform standard model of VTE risk for critically ill patients with tumors was formatted by now. We thus analyzed risk factors of VTE from the perspectives of patient, tumor, and treatment and assessed the predictive value of the ICU-VTE score, which consisted of six independent risk factors (central venous catheterization, 5 points; immobilization ≥ 4 days, 4 points; prior VTE, 4 points; mechanical ventilation, 2 points; lowest hemoglobin during hospitalization ≥ 90 g/L, 2 points; and baseline platelet count > 250,000/μL, 1 points).

Methods

We evaluated the data of tumor patients admitted to the intensive care unit of the Peking University Cancer Hospital between November 2011 and January 2022; 560 cases who received VTE-related screening during hospitalization were chosen for this retrospective study.

Results

The inhospital VTE occurrence rate in our cohort was 55.7% (312/560), with a median interval from ICU admission to VTE diagnosis of 8.0 days. After the multivariate logistic regression analysis, several factors were proved to be significantly associated with inhospital VTE: age ≥ 65 years, high tumor grade (G3–4), medical diseases, fresh frozen plasma transfusion, and anticoagulant prophylaxis. The medium-high risk group according to the ICU-VTE score was positively correlated with VTE when compared with the low-risk group (9–18 points vs. 0–8 points; OR, 3.13; 95% CI, 2.01–4.85, P < 0.001). The AUC of the ICU-VTE scores according to the ROC curve was 0.714 (95% CI, 0.67–0.75, P < 0.001).

Conclusions

The ICU-VTE score, as well as tumor grade, might assist in the assessment of inhospital VTE risk for critically ill patients with tumors. The predictive accuracy might be improved when combining two of them; further follow-up researches are needed to confirm it.
Comparison of short-term outcomes between robotic-assisted and laparoscopic gastrectomy guided by carbon nanoparticle suspension injection in gastric cancer
Authors: Li Zhiyan , Ai Shichao , Wang Feng , Tao Liang , Sun Feng , Song Peng , Shen Xiaofei , Hu Qiongyuan , Li Xianghui , Liu Song , Wang Meng , Guan Wenxian
Published: September 2022

Background

The clinical application of robotic-assisted gastrectomy remains controversial, especially as clinical studies of this operation navigated by carbon nanoparticle suspension injection (CNSI) have not been conducted. This study aims to assess the perioperative safety and efficacy of CNSI-guided robotic-assisted gastrectomy in patients with gastric cancer by focusing on short-term outcomes.

Methods

A retrospective analysis of patients who underwent CNSI-guided laparoscopic or robotic-assisted gastrectomy with a pathological diagnosis of gastric cancer was conducted. Data on demographics, surgical management, clinical-pathological results and short-term outcomes were compared among the groups.

Results

A total of 126 eligible patients were separated into the robotic-assisted gastrectomy (RAG) group (n = 16) and the laparoscopic gastrectomy (LG) group (n = 110) in total. The operation time of the RAG group is longer than the LG group (p = 0.0000). When it comes to perioperative and short-term complications, there exists no statistical difference between the two groups.

Conclusion

The time required for CNSI-guided robotic-assisted gastrectomy is longer than that for CNSI-guided laparoscopic gastrectomy. CNSI-guided robotic-assisted gastrectomy is safe and effective.
Provision of injectable contraceptives by community health workers in sub-Saharan Africa: a systematic review of safety, acceptability and effectiveness
Authors: Ayuk Besong Eric , Yankam Brenda Mbouamba , Saah Farrukh Ishaque , Bain Luchuo Engelbert
Published: September 2022

Background

Injectable contraceptives are the most popular method of contraception in sub-Saharan Africa (SSA), but their availability in clinical settings has been severely limited, despite the scarcity of health care providers and limited access to health facilities. WHO and USAID have endorsed the community-based distribution of injectable contraceptives as a promising option for improving access to family planning services and expanding the method mix for women who want to limit the number of births. Studies have shown that community health workers (CHWs) can provide women with injectable contraceptives that meet acceptable quality standards. The goal of this study is to identify, evaluate and synthesize evidence supporting the use of community-based administration of injectable contraceptives in SSA.

Methods

This review's guidance was based on a previously developed protocol. Nine international electronic databases and the websites of organizations known to support community-based reproductive health initiatives in SSA were searched systemically. Experts in this area were also contacted for the identification of unpublished literature and ongoing studies. The reference lists of eligible studies were reviewed. The Effective Public Practice Project tool was used to assess the quality and risk of bias in eligible studies. Data were extracted and analysed using a custom data extraction form and a narrative synthesis.

Results

The search strategy identified a total of 1358 studies with 12 studies meeting the inclusion criteria. One unpublished study was provided by an expert making a total of 13 studies. The results showed that irrespective of the study designs, well-trained CHWs can competently administer injectable contraceptives safely and community-based delivery of injectable contraceptives is acceptable in SSA. Also, the use of community health workers in the provision of depot-medroxyprogesterone acetate expanded access to inhabitants of hard-to-reach areas and led to an overall uptake of injectable contraceptives as well as family planning. Studies that compared CHWs to clinic-based providers revealed equivalent or higher levels of performance in favour of CHWs.

Conclusions

The CHWs can competently provide injectable contraceptives within SSA communities if appropriately trained and supervised. Hence, SSA policymakers should give this initiative due consideration as a way of improving access to family planning services.
Public health research priorities for WHO on COVID-19 in the South-East Asia Region: results of a prioritization survey
Authors: Azim Tasnim , Bhushan Anjana , Del Rio Vilas Victor J. , Srivastava Rahul , Wijesinghe Pushpa Ranjan , Ofrin Roderico , Chauhan Sharat , Krishnan Anand
Published: September 2022

Background

Effectively addressing the coronavirus disease 2019 (COVID-19) pandemic caused by the new pathogen requires continuous generation of evidence to inform decision-making. Despite an unprecedented amount of research occurring globally, the need to identify gaps in knowledge and prioritize a research agenda that is linked to public health action is indisputable. The WHO South-East Asia Region (SEAR) is likely to have region-specific research needs.

Methods

We aimed to identify a priority research agenda for guiding the regional and national response to the COVID-19 pandemic in SEAR countries. An online, anonymous research prioritization exercise using recent WHO guidance was conducted among the technical staff of WHO’s country and regional offices engaged with the national COVID-19 response during October 2020. They were each asked to contribute up to five priority research ideas across seven thematic areas. These research ideas were reviewed, consolidated and scored by a core group on six parameters: regional specificity, relevance to the COVID-19 response, feasibility within regional research capacity, time to availability for decision-making, likely impact on practice, and promoting equity and gender responsiveness. The total scores for individual suggestions were organized in descending order, and ideas in the upper tertile were considered to be of high priority.

Results

A total of 203 priority research ideas were received from 48 respondents, who were primarily research and emergency response focal points in country and regional offices. These were consolidated into 78 research ideas and scored. The final priority research agenda of 27 items covered all thematic areas—health system (n=10), public health interventions (n=6), disease epidemiology (n=5), socioeconomic and equity (n=3), basic sciences (n=1), clinical sciences (n=1) and pandemic preparedness (n=1).

Conclusions

This exercise, a part of WHO’s mandate to “shape the research agenda”, can help build a research roadmap ensuring efficient use of limited resources. This prioritized research agenda can act as a catalyst for Member States to accelerate research that could impact the COVID-19 response in SEAR.
MICAL2 contributes to gastric cancer cell migration via Cdc42-dependent activation of E-cadherin/β-catenin signaling pathway
Authors: Wang Qianwen , Qi Chenxiang , Min Pengxiang , Wang Yueyuan , Ye Fengwen , Xia Tianxiang , Zhang Yujie , Du Jun
Published: September 2022

Background

Gastric cancer is a common and lethal human malignancy worldwide and cancer cell metastasis is the leading cause of cancer-related mortality. MICAL2, a flavoprotein monooxygenase, is an important regulator of epithelial-to-mesenchymal transition. The aim of this study was to explore the effects of MICAL2 on gastric cancer cell migration and determine the underlying molecular mechanisms.

Methods

Cell migration was examined by wound healing and transwell assays. Changes in E-cadherin/β-catenin signaling were determined by qPCR and analysis of cytoplasmic and nuclear protein fractions. E-cadherin/β-catenin binding was determined by co-immunoprecipitation assays. Cdc42 activity was examined by pulldown assay.

Results

MICAL2 was highly expressed in gastric cancer tissues. The knockdown of MICAL2 significantly attenuated migratory ability and β-catenin nuclear translocation in gastric cancer cells while LiCl treatment, an inhibitor of GSK3β, reversed these MICAL2 knockdown-induced effects. Meanwhile, E-cadherin expression was markedly enhanced in MICAL2-depleted cells. MICAL2 knockdown led to a significant attenuation of E-cadherin ubiquitination and degradation in a Cdc42-dependent manner, then enhanced E-cadherin/β-catenin binding, and reduced β-catenin nuclear translocation.

Conclusions

Together, our results indicated that MICAL2 promotes E-cadherin ubiquitination and degradation, leading to enhanced β-catenin signaling via the disruption of the E-cadherin/β-catenin complex and, consequently, the promotion of gastric cell migration.
A multi-perspective qualitative exploration of the reasons for changes in the physical activity among 10–11-year-old children following the easing of the COVID-19 lockdown in the UK in 2021
Authors: Walker Robert , House Danielle , Emm-Collison Lydia , Salway Ruth , Tibbitts Byron , Sansum Kate , Reid Tom , Breheny Katie , Churchward Sarah , Williams Joanna G. , de Vocht Frank , Hollingworth William , Foster Charlie , Jago Russell
Published: September 2022

Background

Active-6 is exploring how the COVID-19 pandemic has impacted physical activity behaviour among Year 6 children (aged 10–11 years) and their parents in Southwest England. Initial findings from the Active-6 project have shown a 7–8 min decrease in moderate-to-vigorous physical activity and an increase in sedentary behaviour among children following the easing of restrictions in the UK in latter half of 2021. This finding suggests that the pandemic has had a persistent impact on child physical activity behaviour. This paper explored the possible mechanisms behind these changes.

Methods

Interviews with parents (n = 21), members of school staff (n = 9) and focus groups with children aged 10–11 years (n = 47) were conducted between August and December 2021 to discuss the impact of the pandemic on child physical activity behaviour. The framework method was used for analysis.

Results

Five themes spanning two key stages of the pandemic were described. Three themes related to the period of lockdowns and fluctuating restrictions (March 2020 – April 2021). These included: Theme 1) Lockdown: A short-lived adventure; Theme 2) Access to facilities during restrictions; and Theme 3) The importance of the parent. A further two themes were identified related to the period following the gradual easing of restrictions in April 2021. These included: Theme 4) An overwhelming return to normal; and Theme 5) Reopening fatigue.

Conclusions

The analysis suggested that feelings of novelty experienced during the initial stages of lockdown waned as restrictions were prolonged, creating an increasingly challenging period for parents and their children. However, during periods of restrictions, the importance of parental encouragement and access to appropriate facilities in the local and home environment helped facilitate physical activity. Following the easing of COVID-19 restrictions, emotional overwhelm and physical fatigue among children, stemming from a sedentary and socially isolated life in lockdown and other restrictions, were key contributors to the decreased moderate to vigorous physical activity and increased sedentary behaviour that was observed in a related quantitative study.
Identification of diagnostic biomarkers and therapeutic targets in peripheral immune landscape from coronary artery disease
Authors: Feng Xiaoteng , Zhang Yifan , Du Min , Li Sijin , Ding Jie , Wang Jiarou , Wang Yiru , Liu Ping
Published: September 2022

Background

Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD.

Methods

We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis.

Results

A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR−/− mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-β, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway.

Conclusions

We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.
TNFAIP3 mutation causing haploinsufficiency of A20 with a hemophagocytic lymphohistiocytosis phenotype: a report of two cases
Authors: Aslani Nahid , Asnaashari Kosar , Parvaneh Nima , Shahrooei Mohammad , Sotoudeh-Anvari Maryam , Shahram Farhad , Ziaee Vahid
Published: September 2022

Background

A20 haploinsufficiency (HA20) is a newly introduced autosomal dominant autoinflammatory disorder, also known as Behcet’s-like disease. Some of the most common symptoms of the disease are recurrent oral, genital, and/or gastrointestinal (GI) ulcers, episodic fever, musculoskeletal symptoms, cutaneous lesions, and recurrent infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of multi-organ failure due to excessive immune activation. HLH has been reported in a few HA20 patients. Herein, we report two children with the primary presentation of HLH, with a mutation in TNFAIP3, in favor of HA20.

Case presentations

Our first patient was a 4-month-old boy who presented with fever, irritability, pallor, and hepatosplenomegaly. Pancytopenia, elevated ferritin, and decreased fibrinogen levels were found in laboratory evaluation. He was diagnosed with HLH and was treated with methylprednisolone and cyclosporine. Two years later, whole exome sequencing (WES) indicated a mutation in TNFAIP3 at NM_001270507: exon3: c.C386T, p.T129M, consistent with A20 haploinsufficiency. Etanercept, a TNF inhibitor, was prescribed, but the parents were reluctant to initiate the therapy. The patient passed away with the clinical picture of cerebral hemorrhage.

The second patient was a 3-month-old boy who presented with a fever and hepatosplenomegaly. Laboratory evaluation found pancytopenia, hyperferritinemia, hypoalbuminemia, hypertriglyceridemia, and hypofibrinogenemia. With the establishment of the HLH diagnosis, he was treated with etoposide, dexamethasone, and cyclosporine, and recovered. WES results revealed a heterozygous de novo variant of TNFAIP3 (c. T824C in exon 6, 6q23.3) that leads to a proline to leucine amino acid change (p. L275P). He was treated with etanercept and has been symptom-free afterward.

Conclusions

This report is a hypothesis for developing of the HLH phenotype in the presence of TNFAIP3 mutation. Our results provide a new perspective on the role of TNFAIP3 mutation in HLH phenotypes, but more extensive studies are required to confirm these preliminary results.
Kawasaki disease complicated by peripheral artery thrombosis: a case report and literature review
Authors: Zhang Nanjun , Yu Li , Xiong Zhongxian , Hua Yimin , Duan Hongyu , Qiao Lina , Zhou Kaiyu , Wang Chuan
Published: September 2022

Background

Peripheral gangrene is rarely documented as a possible complication of Kawasaki disease (KD). There are many causes of peripheral gangrene, and the common cause is in situ thrombosis or embolism. Most cases are reported to have regrettable outcomes (amputation or necrotic shedding). Herein, we report the successful management of KD complicated by peripheral artery thrombosis in an older Chinese boy, and a review of all cases of peripheral gangrene in KD in the literature.

Case presentation

We found that most of the children with this complication were under 1 year old, had a heavy inflammatory response combined with the use of cortisol and immunoglobulin, and most children had coronary artery lesions. In addition, Peripheral gangrene mainly occurred in the subacute or chronic stage, and the prognosis is poor.

Conclusions

In the presence of high risk factors, we consider it is necessary to monitor coagulation function and administer prophylactic anticoagulation therapy. When peripheral artery thrombosis or embolism occur, heparin and prostaglandins can be used for treatment.
The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration
Authors: Nortey Andrea , Garces Kimberly , Carmy-Bennun Tal , Hackam Abigail S.
Published: September 2022

Background

Retinal degenerative diseases are a group of conditions characterized by photoreceptor death and vision loss. Excessive inflammation and microglial activation contribute to the pathology of retinal degenerations and a major focus in the field is identifying more effective anti-inflammatory therapeutic strategies that promote photoreceptor survival. A major challenge to developing anti-inflammatory treatments is to selectively suppress detrimental inflammation while maintaining beneficial inflammatory responses. We recently demonstrated that endogenous levels of the IL-27 cytokine were upregulated in association with an experimental treatment that increased photoreceptor survival. IL-27 is a pleiotropic cytokine that regulates tissue reactions to infection, neuronal disease and tumors by inducing anti-apoptotic and anti-inflammatory genes and suppressing pro-inflammatory genes. IL-27 is neuroprotective in the brain, but its function during retinal degeneration has not been investigated. In this study, we investigated the effect of IL-27 in the rd10 mouse model of inherited photoreceptor degeneration.

Methods

Male and female rd10 mice were randomly divided into experimental (IL-27) and control (saline) groups and intravitreally injected at age post-natal day (P) 18. Retina function was analyzed by electroretinograms (ERGs), visual acuity by optomotor assay, photoreceptor death by TdT-mediated dUTP nick-end labeling (TUNEL) assay, microglia/macrophage were detected by immunodetection of IBA1 and inflammatory mediators by cytoplex and QPCR analysis. The distribution of IL-27 in the retina was determined by immunohistochemistry on retina cross-sections and primary Muller glia cultures.

Results

We demonstrate that recombinant IL-27 decreased photoreceptor death, increased retinal function and reduced inflammation in the rd10 mouse model of retinal degeneration. Furthermore, IL-27 injections led to lower levels of the pro-inflammatory proteins Ccl22, IL-18 and IL-12. IL-27 expression was localized to Muller glia and IL-27 receptors to microglia, which are key cell types that regulate photoreceptor survival.

Conclusion

Our results identify for the first time anti-inflammatory and neuroprotective activities of IL-27 in a genetic model of retinal degeneration. These findings provide new insight into the therapeutic potential of anti-inflammatory cytokines as a treatment for degenerative diseases of the retina.
Efficacy of behavioral interventions to improve maternal mental health and breastfeeding outcomes: a systematic review
Authors: Pezley Lacey , Cares Kate , Duffecy Jennifer , Koenig Mary Dawn , Maki Pauline , Odoms-Young Angela , Clark Withington Margaret H. , Lima Oliveira Manoela , Loiacono Bernardo , Prough Jilian , Tussing-Humphreys Lisa , Buscemi Joanna
Published: September 2022

Background

Despite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor associated with barriers and reduced rates of breastfeeding intent, initiation, and continuation. Given evidence of a bidirectional association between maternal mental health and breastfeeding, it is important to consider both factors when examining the efficacy of interventions to improve these outcomes. The purpose of this manuscript is to review the literature on the efficacy of behavioral interventions focused on both maternal mental health and breastfeeding outcomes, examining the intersection of the two.

Methods

This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Studies were selected if they were available in English, used primary experimental design, and used a behavioral intervention type to examine maternal mental health and breastfeeding outcomes. Articles were identified from PubMed, CINAHL, Embase, and PsycINFO from database inception to 3 March 2022. Study quality was assessed using the Cochrane Risk of Bias tool. Results were synthesized by intervention success for 1. Mental health and breastfeeding, 2. Breastfeeding only, 3. Mental health only, and 4. No intervention effect. PROSPERO CRD42021224228.

Results

Thirty interventions reported in 33 articles were identified, representing 15 countries. Twelve studies reported statistically significant positive effect of the intervention on both maternal mental health and breastfeeding; most showing a decrease in self-report depressive and/or anxiety symptoms in parallel to an increase in breastfeeding duration and/or exclusivity. Common characteristics of successful interventions were a) occurring across pregnancy and postpartum, b) delivered by hospital staff or multidisciplinary teams, c) offered individually, and d) designed to focus on breastfeeding and maternal mental health or on breastfeeding only. Our results are not representative of all countries, persons, experiences, circumstances, or physiological characteristics.

Conclusions

Interventions that extend the perinatal period and offer individualized support from both professionals and peers who collaborate through a continuum of settings (e.g., health system, home, and community) are most successful in improving both mental health and breastfeeding outcomes. The benefits of improving these outcomes warrant continued development and implementation of such interventions.

Systematic review registration

PROSPERO CRD42021224228.