bluuebunny/crossref_metadata_2025_split huggingface dataset:
RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway
Authors: Shi Rui , Liu Zirong 
Published: April 2022

Abstract
Backround
RPL15 has been found to participate in human tumorigenesis. However, its function and regulatory mechanism in hepatocellular carcinoma (HCC) development are still unclear. Current study investigated the effects of RPL15 in HCC.

Methods
The expression of RPL15 in clinical tissues and cell lines of HCC was detected by RT-qPCR, Western blotting, and Immunohistochemistry (IHC). Colony formation, CCK-8, flow cytometry, Wound healing and Transwell invasion assays, were used to detect the carcinoma progression of HCC cells with RPL15 overexpression or knockdown in vitro. A xenograft model was constructed to assess the effect of RPL15 knockdown on HCC cells in vivo. The expression of CDK2 and Cyclin E1 related to cell cycles, Bax and Bcl-2 related to cell apoptosis, E-cadherin, N-cadherin and Vimentin related to epithelial–mesenchymal transition (EMT), p53 and p21 related to p53 signaling pathway, were detected by Western blotting. The connection between p53, MDM2 and RPL5/11 affected by RPL15 was analyzed using immunoprecipitation and Cycloheximide (CHX) chase assay.

Results
Elevated RPL15 was identified in HCC tissues, which was not only a prediction for the poor prognosis of HCC patients, but also associated with the malignant progression of HCC. RPL15 silencing arrested HCC cell cycle, suppressed HCC cell colony formation, proliferation, invasion, and migration, and induce cell apoptosis. On the contrary, RPL15 upregulation exerted opposite effects. Results also indicated that HCC cell invasion and migration were associated with EMT, and that the RPs-MDM2-p53 pathway was implicated in RPL15-mediated oncogenic transformation. In addition, RPL15 knockdown significantly suppressed HCC xenografts growth.

Conclusions
RPL15 played crucial roles in HCC progression and metastasis, serving as a promising candidate for targeted therapies.
From inflammatory bowel disease to colorectal cancer: what’s the role of miRNAs?
Authors: Vaghari-Tabari Mostafa , Targhazeh Niloufar , Moein Soheila , Qujeq Durdi , Alemi Forough , Majidina Maryam , Younesi Simin , Asemi Zatollah , Yousefi Bahman 
Published: April 2022

AbstractInflammatory Bowel Disease (IBD) is a chronic inflammatory disease with relapse and remission periods. Ulcerative colitis and Crohn’s disease are two major forms of the disease. IBD imposes a lot of sufferings on the patient and has many consequences; however, the most important is the increased risk of colorectal cancer, especially in patients with Ulcerative colitis. This risk is increased with increasing the duration of disease, thus preventing the progression of IBD to cancer is very important. Therefore, it is necessary to know the details of events contributed to the progression of IBD to cancer. In recent years, the importance of miRNAs as small molecules with 20–22 nucleotides has been recognized in pathophysiology of many diseases, in which IBD and colorectal cancer have not been excluded. As a result, the effectiveness of these small molecules as therapeutic target is hopefully confirmed. This paper has reviewed the related studies and findings about the role of miRNAs in the course of events that promote the progression of IBD to colorectal carcinoma, as well as a review about the effectiveness of some of these miRNAs as therapeutic targets.
B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer
Authors: Zhou Bin , Lu Youwei , Zhao Zhiming , Shi Tongguo , Wu Hongya , Chen Weichang , Zhang Liang , Zhang Xueguang 
Published: April 2022

Abstract
Introduction
B7-H4 is overexpressed in colorectal cancer (CRC) and plays an important role in tumor growth and immunosuppression. However, the exact mechanism that regulates B7-H4 expression remains largely unknown. Here, we investigated whether protein kinase C δ (PKCδ) regulates the expression of B7-H4 in CRC.

Methods
By using immunohistochemical (IHC) and immunofluorescence (IF) staining, we analyzed the expression of B7-H4 and phospho-PKCδ (p-PKCδ) in 225 colorectal tumor samples and determined the clinical significance of the expression patterns. In vitro experiments were performed with the CRC cell lines HCT116 and SW620 to detect the effect of PKCδ activation on B7-H4 expression, and xenograft-bearing mice were treated with rottlerin to monitor the expression of B7-H4 and tumor metastasis.

Results
The B7-H4 expression level was significantly correlated with the p-PKCδ level (r = 0.378, P < 0.001) in tumor tissues. Coexpression of p-PKCδ and B7-H4 was significantly associated with moderate/poor differentiation (P = 0.024), lymph node metastasis (P = 0.001) and advanced Dukes’ stage (P = 0.002). Western blot analysis showed that Phorbol-12-Myristate-13-Acetate (TPA) increased B7-H4 expression in a concentration-dependent manner and that rottlerin abrogated the TPA-induced increase in B7-H4 expression. The protein levels of B7-H4 and p-STAT3 were significantly reduced by a PKCδ-specific siRNA. Moreover, the STAT3 inhibitor cryptotanshinone significantly decreased the B7-H4 protein level in CRC cells. Knockdown of B7-H4 or PKCδ suppressed cell migration and motility. Rottlerin also inhibited B7-H4 expression and tumor metastasis in vivo.

Conclusion
The B7-H4 expression level is significantly correlated with the p-PKCδ level and tumor metastasis in CRC samples. B7-H4 expression is upregulated by STAT3 activation via PKCδ and plays roles in PKCδ-induced cancer cell motility and metastasis, suggesting that the PKCδ/STAT3/B7-H4 axis may be a potential therapeutic target for CRC.
Community health workers and health equity in low- and middle-income countries: systematic review and recommendations for policy and practice
Authors: Ahmed Sonia , Chase Liana E. , Wagnild Janelle , Akhter Nasima , Sturridge Scarlett , Clarke Andrew , Chowdhary Pari , Mukami Diana , Kasim Adetayo , Hampshire Kate 
Published: April 2022

Abstract
Background
The deployment of Community Health Workers (CHWs) is widely promoted as a strategy for reducing health inequities in low- and middle-income countries (LMIC). Yet there is limited evidence on whether and how CHW programmes achieve this. This systematic review aimed to synthesise research findings on the following questions: (1) How effective are CHW interventions at reaching the most disadvantaged groups in LMIC contexts? and (2) What evidence exists on whether and how these programmes reduce health inequities in the populations they serve?

Methods
We searched six academic databases for recent (2014–2020) studies reporting on CHW programme access, utilisation, quality, and effects on health outcomes/behaviours in relation to potential stratifiers of health opportunities and outcomes (e.g., gender, socioeconomic status, place of residence). Quantitative data were extracted, tabulated, and subjected to meta-analysis where appropriate. Qualitative findings were synthesised using thematic analysis.

Results
One hundred sixty-seven studies met the search criteria, reporting on CHW interventions in 33 LMIC. Quantitative synthesis showed that CHW programmes successfully reach many (although not all) marginalized groups, but that health inequalities often persist in the populations they serve. Qualitative findings suggest that disadvantaged groups experienced barriers to taking up CHW health advice and referrals and point to a range of strategies for improving the reach and impact of CHW programmes in these groups. Ensuring fair working conditions for CHWs and expanding opportunities for advocacy were also revealed as being important for bridging health equity gaps.

Conclusion
In order to optimise the equity impacts of CHW programmes, we need to move beyond seeing CHWs as a temporary sticking plaster, and instead build meaningful partnerships between CHWs, communities and policy-makers to confront and address the underlying structures of inequity.

Trial registration
PROSPERO registration number CRD42020177333.
Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery
Authors: Draxler Dominik F. , Hanafi Gryselda , Zahra Saffanah , McCutcheon Fiona , Ho Heidi , Keragala Charithani B. , Liu Zikou , Daly David , Painter Thomas , Wallace Sophia , Plebanski Magdalena , Myles Paul S. , Medcalf Robert L. 
Published: April 2022

AbstractBackgroundTranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery.MethodsPatients undergoing lower limb surgery were enrolled into the “Tranexamic Acid in Lower Limb Arthroplasty” (TALLAS) pilot study. The cellular immune response was characterised longitudinally pre- and post-operatively using full blood examination (FBE) and comprehensive immune cell phenotyping by flowcytometry. Red blood cells and platelets were determined in the FBE and levels of T cell cytokines and the plasmin-antiplasmin complex determined using ELISA.ResultsTXA administration increased the proportion of circulating CD141+ conventional dendritic cells (cDC) on post-operative day (POD) 3. It also reduced the expression of CD83 and TNFR2 on classical monocytes and levels of circulating IL-10 at the end of surgery (EOS) time point, whilst increasing the expression of CCR4 on natural killer (NK) cells at EOS, and reducing TNFR2 on POD-3 on NK cells. Red blood cells and platelets were decreased to a lower extent at POD-1 in the TXA group, representing reduced blood loss.ConclusionIn this investigation we have extended our examination on the immunomodulatory effects of TXA in surgery by also characterising the end of surgery time point and including B cells and neutrophils in our immune analysis, elucidating new immunophenotypic changes in phagocytes as well as NK cells. This study enhances our understanding of TXA-mediated effects on the haemostatic and immune response in surgery, validating changes in important functional immune cell subsets in orthopaedic patients.
Neutrophil degranulation and myocardial infarction
Authors: Zhang Nan , Aiyasiding Xiahenazi , Li Wen-jing , Liao Hai-han , Tang Qi-zhu 
Published: April 2022

AbstractMyocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies.
Graphical abstract
Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP‐8, MMP‐9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP‐8); Matrix metalloproteinase 9 (MMP‐9).
Cisplatin resistance-related multi-omics differences and the establishment of machine learning models
Authors: Sui Qihai , Chen Zhencong , Hu Zhengyang , Huang Yiwei , Liang Jiaqi , Bi Guoshu , Bian Yunyi , Zhao Mengnan , Zhan Cheng , Lin Zongwu , Wang Qun , Tan Lijie 
Published: April 2022

AbstractObjectivesPlatinum-based chemotherapies are currently the first-line treatment of non-small cell lung cancer. This study will improve our understanding of the causes of resistance to cisplatin, especially in lung adenocarcinoma (LUAD) and provide a reference for therapeutic decisions in clinical practice.MethodsCancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA) and Zhongshan hospital affiliated to Fudan University (zs-cohort) were used to identify the multi-omics differences related to platinum chemotherapy. Cisplatin-resistant mRNA and miRNA models were constructed by Logistic regression, classification and regression tree and C4.5 decision tree classification algorithm with previous feature selection performed via least absolute shrinkage and selection operator (LASSO). qRT-PCR and western-blotting of A549 and H358 cells, as well as single-cell Seq data of tumor samples were applied to verify the tendency of certain genes.Results661 cell lines were divided into three groups according to the IC50 value of cisplatin, and the top 1/3 (220) with a small IC50 value were defined as the sensitive group while the last 1/3 (220) were enrolled in the insensitive group. TP53 was the most common mutation in the insensitive group, in contrast to TTN in the sensitive group. 1348 mRNA, 80 miRNA, and 15 metabolites were differentially expressed between 2 groups (P < 0.05). According to the LASSO penalized logistic modeling, 6 of the 1348 mRNAs, FOXA2, BATF3, SIX1, HOXA1, ZBTB38, IRF5, were selected as the associated features with cisplatin resistance and for the contribution of predictive mRNA model (all of adjusted P-values < 0.001). Three of 6 (BATF3, IRF5, ZBTB38) genes were finally verified in cell level and patients in zs-cohort.ConclusionsSomatic mutations, mRNA expressions, miRNA expressions, metabolites and methylation were related to the resistance of cisplatin. The models we created could help in the prediction of the reaction and prognosis of patients given platinum-based chemotherapies.
The global prevalence of oropharyngeal dysphagia in different populations: a systematic review and meta-analysis
Authors: Rajati Fatemeh , Ahmadi Nassim , Naghibzadeh Zahra Al-sadat , Kazeminia Mohsen 
Published: April 2022

Abstract
Background
Oropharyngeal dysphagia (OD) refers to any abnormality in the physiology of swallowing in the upper gastrointestinal tract, which leads to the related clinical complications, such as malnutrition, dehydration, and sever complication, such as aspiration pneumonia, suffocation, and eventually, premature death. The previous studies indicated a various range of prevalence of OD. The present systematic review and meta-analysis aimed to standardize the global prevalence of OD in different populations.

Methods
A systematic literature review was conducted using Embase, Scopus, PubMed, Web of Science (WoS) databases, and Google Scholar motor engine using related MeSH/Emtree and Free Text words, with no time limitation until November 2021. The heterogeneity among studies was quantified using I2 index and the random effects model was used, due to the high heterogeneity among the results of studies included in the meta-analysis.

Results
The systematic literature search retrieved 2092 studies. After excluding the irrelevant studies, ultimately 27 articles with a sample size of 9841 were included in the meta-analysis. After combining the studies, the overall estimate of the global prevalence rate of OD was 43.8% (95% CI 33.3–54.9%) and the highest prevalence rate was estimated in Africa with 64.2% (95% CI 53.2–73.9%). Given the subgroup analysis based on the study population, the highest prevalence of OD was related to Dementia with 72.4% (95% CI 26.7–95.0%). The results of meta-regression indicated that the prevalence of OD has an increasing trend with the enhancement of year of publication and mean age.

Conclusion
The results of the present systematic review and meta-analysis revealed that the prevalence of OD is high in different populations and its trend has been increasing in recent years. Therefore, the appropriate strategies should be applied to reduce the prevalence of OD by finding its causation and monitoring at all levels, as well as providing feedback to hospitals.
Recommendations for breastfeeding during Coronavirus Disease 2019 (COVID-19) pandemic
Authors: Liu Xiyao , Chen Haoyue , An Meijing , Yang Wangxing , Wen Yujie , Cai Zhihuan , Wang Lulu , Zhou Qianling 
Published: April 2022

Abstract
Background
Coronavirus Disease 2019 (COVID-19) has spread worldwide. The safety of breastfeeding of SARS-CoV-2-positive women has not yet reached a consensus among the scientific community, healthcare providers, experts in lactation care, health organizations and governments. This study was conducted to summarize the latest evidence about the safety of breastfeeding among suspected/confirmed infected mothers and to summarize the recommendations on breastfeeding during COVID-19 from different organizations.

Methods
A comprehensive literature review of publications about the safety of breastfeeding among SARS-CoV-2-infected mothers was conducted. Scientific databases were searched up to 26 May 2021. The evidence was summarized into five perspectives according to a framework proposed by van de Perre et al. with certain modifications. Moreover, websites of different health organizations were visited to gather the recommendations for breastfeeding.

Results
The current evidence demonstrated that the majority of infants breastfed by infected mothers were negative for SARS-CoV-2. Breast milk samples from suspected/infected mothers mainly demonstrated negative results in SARS-CoV-2 viral tests. There was insufficient evidence proving the infectivity of breast milk from infected mothers. Recent studies found other transmission modalities (e.g., milk containers, skin) associated with breastfeeding. Specific antibodies in the breast milk of infected mothers were also found, implying protective effects for their breastfed children. According to van de Perre’s criteria, the breast milk of infected mothers was unlikely to transmit SARS-CoV-2. Owing to the low quality of the current evidence, studies with a more robust design are needed to strengthen the conclusion regarding the safety of breastfeeding. Further studies to follow up the health status of infants who were directly breastfed by their suspected/infected mothers, to collect breast milk samples at multiple time points for viral tests and to examine specific antibodies in breast milk samples are warranted. Current recommendations on breastfeeding during COVID-19 from different organizations are controversial, while direct breastfeeding with contact precautions is generally suggested as the first choice for infected mothers.

Conclusions
This review determined the safety of breastfeeding and identified the focus for further research during the COVID-19 pandemic. Recommendations on breastfeeding are suggested to be updated in a timely manner according to the latest evidence.
Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation
Authors: Deycmar Simon , Mara Elisabeth , Kerschbaum-Gruber Sylvia , Waller Verena , Georg Dietmar , Pruschy Martin 
Published: April 2022

Abstract
Objective
Hypersensitivity towards proton versus photon irradiation was demonstrated in homologous recombination repair (HRR)-deficient cell lines. Hence, combined treatment concepts targeting HRR provide a rational for potential pharmaceutical exploitation. The HSP90 inhibitor ganetespib (STA-9090) downregulates a multitude of HRR-associated proteins and sensitizes for certain chemotherapeutics. Thus, the radiosensitizing effect of HSP90-inhibiting ganetespib was investigated for reference photon irradiation and proton irradiation at a proximal and distal position in a spread-out Bragg peak (SOBP).

Methods
A549 and FaDu cells were treated with low-dose (2 nM resp. 1 nM) ganetespib and irradiated with 200 kV photons. Proton irradiation was performed at a proximal and a distal position within a SOBP, with corresponding dose-averaged linear-energy transfer (LETD) values of 2.1 and 4.5 keV/µm, respectively. Cellular survival data was fitted to the linear-quadratic model to calculate relative biological effectiveness (RBE) and the dose-modifying factor (DMF). Additionally, A549 cells were treated with increasing doses of ganetespib and investigated by flow cytometry, immunoblotting, and immunofluorescence microscopy to investigate cell cycle distribution, Rad51 protein levels, and γH2AX foci, respectively.

Results
Low-dosed ganetespib significantly sensitized both cancer cell lines exclusively for proton irradiation at both investigated LETD, resulting in increased RBE values of 10–40%. In comparison to photon irradiation, the fraction of cells in S/G2/M phase was elevated in response to proton irradiation with 10 nM ganetespib consistently reducing this population. No changes in cell cycle distribution were detected in unirradiated cells by ganetespib alone. Protein levels of Rad51 are downregulated in irradiated A549 cells by 10 nM and also 2 nM ganetespib within 24 h. Immunofluorescence staining demonstrated similar induction and removal of γH2AX foci, irrespective of irradiation type or ganetespib administration.

Conclusion
Our findings illustrate a proton-specific sensitizing effect of low-dosed ganetespib in both employed cell lines and at both investigated SOBP positions. We provide additional experimental data on cellular response and a rational for future combinatorial approaches with proton radiotherapy.