bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical teaching of university-degree nursing students: are the nurses in practice in Uganda ready?
Authors: Drasiku Amos , Gross Janet L. , Jones Casey , Nyoni Champion N. 
Published: January 2021

AbstractBackgroundNurses with degree qualifications offer better nursing care compared to nurses prepared at lower levels. University based nursing degrees have been sanctioned as entry into professional nursing and several low-resource states have introduced university based nursing degrees. The clinical teaching of students enrolled in such degrees is challenged, as most nurses in practice do not have university degrees and may not have the necessary skills to facilitate clinical learning as expected at degree level. A university in Uganda established a bachelor’s degree in Nursing program and was expecting to use nurses in practice at a teaching hospital for the clinical teaching of university-degree nursing students. This study reports on the perceptions of the nurses in practice regarding their readiness for the clinical teaching of undergraduate nursing students.MethodsA qualitative descriptive research study was conducted among 33 conveniently sampled nurses from Arua Regional Referral Hospital (ARRH) who had been supervising Diploma and/or Certificate in Nursing students. Five focus group discussions and three informant interviews were used to generate the data. Data were transcribed verbatim and analysed using an inductive approach through thematic analysis.ResultsThe nurses in practice perceived themselves as ready for clinical teaching of undergraduate nursing students. Three themes emerged namely; “Willingness to teach undergraduate students” “Perceived attributes of undergraduate students”, and “The clinical practice environment”.ConclusionThe nurses in practice need support in the execution of the clinical teaching role of university-degree nursing students. The nature of supports would include, continuing professional development specific to clinical teaching, engaging the educators in the clinical environment, positively engaging power gradients and address insecurities among the nurses and the students. Students in these programmes should be exposed to the clinical environment earlier within the programme, and be exposed to interprofessional and trans-professional education.
A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred
Authors: Ahmed Ashfaque , Wang Meng , Khan Rizwan , Shah Abid Ali , Guo Hui , Malik Sajid , Xia Kun , Hu Zhengmao 
Published: January 2021

Abstract
Background
Hearing loss/deafness is a common otological disorder found in the Pakistani population due to the high prevalence of consanguineous unions, but the full range of genetic causes is still unknown.

Methods
A large consanguineous Pakistani kindred with hearing loss was studied. Whole-exome sequencing and Sanger sequencing were performed to search for the candidate gene underlying the disease phenotype. A minigene assay and reverse transcription polymerase chain reaction was used to assess the effect of splicing variants.

Results
The splicing variants of OTOF (NM_194248, c.3289-1G>T) cosegregated with the disease phenotype in this Pakistani family. The substitution of a single base pair causes the deletion of 10 bp (splicing variant 1) or 13 bp (splicing variant 2) from exon 27, which results in truncated proteins of 1141 and 1140 amino acids, respectively.

Conclusion
Our findings reveal an OTOF splice-site variant as pathogenic for profound hearing loss in this family.
Leptin Receptor (LEPR) promotes proliferation, migration, and invasion and inhibits apoptosis in hepatocellular carcinoma by regulating ANXA7
Authors: Huang He , Zhang Jun , Ling Fei , Huang Yuhong , Yang Min , Zhang Yao , Wei Yuanyi , Zhang Qingqing , Wang Honghai , Song Lin , Wu Ying , Yang Jiayu , Tang Jianwu 
Published: January 2021

Abstract
Background
Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. However, the role of LEPR and its underlying mechanisms in lymphatic metastasis of hepatocarcinoma have not yet been studied.

Methods
We performed bioinformatics analysis, qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent, coimmunoprecipitation assays and a series of functional assays to investigate the roles of LEPR in hepatocellular carcinoma.

Results
We discovered that LEPR was highly expressed in liver cancer tissues, and the expression of LEPR in Hca-F cells was higher than that in Hca-P cells. Furthermore, LEPR promotes the proliferation, migration and invasion and inhibits the apoptosis of hepatocarcinoma lymphatic metastatic cells. Further studies indicated that LEPR interacts with ANXA7. Mechanistically, LEPR regulated ERK1/2 and JAK2/STAT3 expression via ANXA7 regulation.

Conclusions
These findings unveiled a previously unappreciated role of LEPR in the regulation of lymphatic metastatic hepatocellular carcinoma, assigning ANXA7-LEPR as a promising therapeutic target for liver cancer treatments.
Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy
Authors: Bhat Ajaz A. , Nisar Sabah , Maacha Selma , Carneiro-Lobo Tatiana Correa , Akhtar Sabah , Siveen Kodappully Sivaraman , Wani Nissar A. , Rizwan Arshi , Bagga Puneet , Singh Mayank , Reddy Ravinder , Uddin Shahab , Grivel Jean-Charles , Chand Gyan , Frenneaux Michael P. , Siddiqi Mushtaq A. , Bedognetti Davide , El-Rifai Wael , Macha Muzafar A. , Haris Mohammad 
Published: January 2021

AbstractEsophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases among patients with advanced disease account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, and growth factors, which play a significant role in supporting the growth and aggressive behavior of cancer cells. The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. The molecular changes in the TME are used as biological markers for diagnosis, prognosis, and response to treatment in patients. This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development. In addition, it discusses the wide range of changes and intracellular signaling pathways that occur in the TME. Overall, this is a relatively unexplored field that could provide crucial insights into tumor immunology and encourage the effective application of modulatory cytokine-chemokine therapy to EC.
TNFα priming through its interaction with TNFR2 enhances endothelial progenitor cell immunosuppressive effect: new hope for their widespread clinical application
Authors: Nouri Barkestani Mahsa , Shamdani Sara , Afshar Bakshloo Mazdak , Arouche Nassim , Bambai Bijan , Uzan Georges , Naserian Sina 
Published: January 2021

Abstract
Background
Bone marrow derived endothelial progenitor cells (EPCs) are immature endothelial cells (ECs) involved in neo-angiogenesis and endothelial homeostasis and are considered as a circulating reservoir for endothelial repair. Many studies showed that EPCs from patients with cardiovascular pathologies are impaired and insufficient; hence, allogenic sources of EPCs from adult or cord blood are considered as good choices for cell therapy applications. However, allogenic condition increases the chance of immune rejection, especially by T cells, before exerting the desired regenerative functions. TNFα is one of the main mediators of EPC activation that recognizes two distinct receptors, TNFR1 and TNFR2. We have recently reported that human EPCs are immunosuppressive and this effect was TNFα-TNFR2 dependent. Here, we aimed to investigate if an adequate TNFα pre-conditioning could increase TNFR2 expression and prime EPCs towards more immunoregulatory functions.

Methods
EPCs were pre-treated with several doses of TNFα to find the proper dose to up-regulate TNFR2 while keeping the TNFR1 expression stable. Then, co-cultures of human EPCs and human T cells were performed to assess whether TNFα priming would increase EPC immunosuppressive and immunomodulatory effect.

Results
Treating EPCs with 1 ng/ml TNFα significantly up-regulated TNFR2 expression without unrestrained increase of TNFR1 and other endothelial injury markers. Moreover, TNFα priming through its interaction with TNFR2 remarkably enhanced EPC immunosuppressive and anti-inflammatory effects. Conversely, blocking TNFR2 using anti-TNFR2 mAb followed by 1 ng/ml of TNFα treatment led to the TNFα-TNFR1 interaction and polarized EPCs towards pro-inflammatory and immunogenic functions.

Conclusions
We report for the first time the crucial impact of inflammation notably the TNFα-TNFR signaling pathway on EPC immunological function. Our work unveils the pro-inflammatory role of the TNFα-TNFR1 axis and, inversely the anti-inflammatory implication of the TNFα-TNFR2 axis in EPC immunoregulatory functions. Priming EPCs with 1 ng/ml of TNFα prior to their administration could boost them toward a more immunosuppressive phenotype. This could potentially lead to EPCs’ longer presence in vivo after their allogenic administration resulting in their better contribution to angiogenesis and vascular regeneration.
The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis
Authors: Wormgoor Marjon E. A. , Rodenburg Sanne C. 
Published: January 2021

Abstract
Background
Due to the inconsistent use of diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), it is unsure whether physiotherapeutic management regarded effective in ME/CFS is appropriate for patients diagnosed with criteria that consider post-exertional malaise (PEM) as a hallmark feature.

Purpose
To appraise current evidence of the effects of physiotherapy on symptoms and functioning in ME/CFS patients in view of the significance of PEM in the applied diagnostic criteria for inclusion.

Methods
A systematic review of randomized controlled trials published over the last two decades was conducted. Studies evaluating physiotherapeutic interventions for adult ME/CFS patients were included. The diagnostic criteria sets were classified into three groups according to the extent to which the importance of PEM was emphasized: chronic fatigue (CF; PEM not mentioned as a criterion), CFS (PEM included as an optional or minor criterion) or ME (PEM is a required symptom). The main results of included studies were synthesized in relation to the classification of the applied diagnostic criteria. In addition, special attention was given to the tolerability of the interventions.

Results
Eighteen RCTs were included in the systematic review: three RCTs with CF patients, 14 RCTs with CFS patients and one RCT covering ME patients with PEM. Intervention effects, if any, seemed to disappear with more narrow case definitions, increasing objectivity of the outcome measures and longer follow-up.

Conclusion
Currently, there is no scientific evidence when it comes to effective physiotherapy for ME patients. Applying treatment that seems effective for CF or CFS patients may have adverse consequences for ME patients and should be avoided.
Obesity and COVID-19: what makes obese host so vulnerable?
Authors: Mohammad Sameer , Aziz Rafia , Al Mahri Saeed , Malik Shuja Shafi , Haji Esraa , Khan Altaf Husain , Khatlani Tanvir Saleem , Bouchama Abderrezak 
Published: January 2021

AbstractThe disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.
Predicting risk of early discontinuation of exclusive breastfeeding at a Brazilian referral hospital for high-risk neonates and infants: a decision-tree analysis
Authors: Silva Maíra Domingues Bernardes , de Oliveira Raquel de Vasconcellos Carvalhaes , da Silveira Barroso Alves Davi , Melo Enirtes Caetano Prates 
Published: January 2021

Abstract
Background
Determinants at several levels may affect breastfeeding practices. Besides the known historical, socio-economic, cultural, and individual factors, other components also pose major challenges to breastfeeding. Predicting existing patterns and identifying modifiable components are important for achieving optimal results as early as possible, especially in the most vulnerable population. The goal of this study was building a tree-based analysis to determine the variables that can predict the pattern of breastfeeding at hospital discharge and at 3 and 6 months of age in a referral center for high-risk infants.

Methods
This prospective, longitudinal study included 1003 infants and was conducted at a high-risk public hospital in the following three phases: hospital admission, first visit after discharge, and monthly telephone interview until the sixth month of the infant’s life. Independent variables were sorted into four groups: factors related to the newborn infant, mother, health service, and breastfeeding. The outcome was breastfeeding as per the categories established by the World Health Organization (WHO). For this study, we performed an exploratory analysis at hospital discharge and at 3 and at 6 months of age in two stages, as follows: (i) determining the frequencies of baseline characteristics stratified by breastfeeding indicators in the three mentioned periods and (ii) decision-tree analysis.

Results
The prevalence of exclusive breastfeeding (EBF) was 65.2% at hospital discharge, 51% at 3 months, and 20.6% at 6 months. At hospital discharge and the sixth month, the length of hospital stay was the most important predictor of feeding practices, also relevant at the third month. Besides the mother’s and child’s characteristics (multiple births, maternal age, and parity), the social context, work, feeding practice during hospitalization, and hospital practices and policies on breastfeeding influenced the breastfeeding rates.

Conclusions
The combination algorithm of decision trees (a machine learning technique) provides a better understanding of the risk predictors of breastfeeding cessation in a setting with a large variability in expositions. Decision trees may provide a basis for recommendations aimed at this high-risk population, within the Brazilian context, in light of the hospital stay at a neonatal unit and period of continuous feeding practice.
Nutritional supplements and mother’s milk composition: a systematic review of interventional studies
Authors: Keikha Mojtaba , Shayan-Moghadam Ramin , Bahreynian Maryam , Kelishadi Roya 
Published: January 2021

Abstract
Background
This study aims to systematically review the effects of maternal vitamin and/or mineral supplementation on the content of breast milk.

Methods
We systematically searched electronic databases including Medline via PubMed, Scopus and ISI Web of Science till May 24, 2018. The following terms were used systematically in all mentioned databases: (“human milk” OR “breast milk” OR “breast milk composition” OR “human breast milk composition” OR “composition breast milk” OR “mother milk” OR “human breast milk” OR “maternal milk”) AND (“vitamin a” OR “retinol” OR “retinal” OR “retinoic acid” OR “beta-carotene” OR “beta carotene” OR “ascorbic acid” OR “l-ascorbic acid” OR “l ascorbic acid” OR “vitamin c” OR “vitamin d” OR “cholecalciferol” OR “ergocalciferol” OR “calciferol” OR “vitamin e” OR “tocopherol” OR “tocotrienol” OR “alpha-tocopherol” OR “alpha tocopherol” OR “α-tocopherol” OR “α tocopherol” OR “vitamin k” OR “vitamin b” OR “vitamin b complex” OR “zinc” OR “iron” OR “copper” Or “selenium” OR “manganese” OR “magnesium”) and we searched Medline via Medical subject Headings (MeSH) terms. We searched Google Scholar for to increase the sensitivity of our search. The search was conducted on human studies, but it was not limited to the title and abstract. Methodological quality and risk of bias of included studies were evaluated by Jadad scale and Cochrane risk of bias tools, respectively.

Results
This review included papers on three minerals (zinc, iron, selenium) and 6 vitamins (vitamin A, B, D, C, E and K) in addition to multi-vitamin supplements. Although studies had different designs, e.g. not using random allocation and/or blinding, our findings suggest that maternal use of some dietary supplements, including vitamin A, D, vitamin B1, B2 and vitamin C might be reflected in human milk. Vitamin supplements had agreater effect on breast milk composition compared to minerals. Higher doses of supplements showed higher effects and they were reflected more in colostrum than in the mature milk.

Conclusion
Maternal dietary vitamin and/or mineral supplementation, particularly fat- soluble vitamins, vitamin B1, B2 and C might be reflected in the breast milk composition. No difference was found between mega dose and single dose administration of minerals.
ASC-J9® suppresses prostate cancer cell proliferation and invasion via altering the ATF3-PTK2 signaling
Authors: Tian Hao , Chou Fu-ju , Tian Jing , Zhang Yong , You Bosen , Huang Chi-Ping , Yeh Shuyuan , Niu Yuanjie , Chang Chawnshang 
Published: January 2021

Abstract
Background
Early studies indicated that ASC-J9®, an androgen receptor (AR) degradation enhancer, could suppress the prostate cancer (PCa) progression. Here we found ASC-J9® could also suppress the PCa progression via an AR-independent mechanism, which might involve modulating the tumor suppressor ATF3 expression.

Methods
The lentiviral system was used to modify gene expression in C4–2, CWR22Rv1 and PC-3 cells. Western blot and Immunohistochemistry were used to detect protein expression. MTT and Transwell assays were used to test the proliferation and invasion ability.

Results
ASC-J9® can suppress PCa cell proliferation and invasion in both PCa C4–2 and CWR22Rv1 cells via altering the ATF3 expression. Further mechanistic studies reveal that ASC-J9® can increase the ATF3 expression via decreasing Glutamate-cysteine ligase catalytic (GCLC) subunit expression, which can then lead to decrease the PTK2 expression. Human clinical studies further linked the ATF3 expression to the PCa progression. Preclinical studies using in vivo mouse model also proved ASC-J9® could suppress AR-independent PCa cell invasion, which could be reversed after suppressing ATF3.

Conclusions
ASC-J9® can function via altering ATF3/PTK2 signaling to suppress the PCa progression in an AR-independent manner.
Hepatitis B virus P protein initiates glycolytic bypass in HBV-related hepatocellular carcinoma via a FOXO3/miRNA-30b-5p/MINPP1 axis
Authors: Chen Wenbiao , Jiang Jingjing , Gong Lan , Shu Zheyue , Xiang Dairong , Zhang Xujun , Bi Kefan , Diao Hongyan 
Published: January 2021

Abstract
Background
Hepatitis B virus (HBV) infection is a crucial risk factor for hepatocellular carcinoma (HCC). However, its underlying mechanism remains understudied.

Methods
Microarray analysis was conducted to compare the genes and miRNAs in liver tissue from HBV-positive and HBV-negative HCC patients. Biological functions of these biomarkers in HBV-related HCC were validated via in vitro and in vivo experiments. Furthermore, we investigated the effect of HBV on the proliferation and migration of tumor cells in HBV-positive HCC tissue. Bioinformatics analysis was then performed to validate the clinical value of the biomarkers in a large HCC cohort.

Results
We found that a gene, MINPP1 from the glycolytic bypass metabolic pathway, has an important biological function in the development of HBV-positive HCC. MINPP1 is down-regulated in HBV-positive HCC and could inhibit the proliferation and migration of the tumor cells. Meanwhile, miRNA-30b-5p was found to be a stimulator for the proliferation of tumor cell through glycolytic bypass in HBV-positive HCC. More importantly, miRNA-30b-5p could significantly downregulate MINPP1 expression. Metabolic experiments showed that the miRNA-30b-5p/MINPP1 axis is able to accelerate the conversion of glucose to lactate and 2,3-bisphosphoglycerate (2,3-BPG). In the HBV-negative HCC cells, miRNA-30b-5p/MINPP1 could not regulate the glycolytic bypass to promote the tumorigenesis. However, once HBV was introduced into these cells, miRNA-30b-5p/MINPP1 significantly enhanced the proliferation, migration of tumor cells, and promoted the glycolytic bypass. We further revealed that HBV infection promoted the expression of miRNA-30b-5p through the interaction of HBV protein P (HBp) with FOXO3. Bioinformatics analysis on a large cohort dataset showed that high expression of MINPP1 was associated with favorable survival of HBV-positive HCC patients, which could lead to a slower progress of this disease.

Conclusion
Our study found that the HBp/FOXO3/miRNA-30b-5p/MINPP1 axis contributes to the development of HBV-positive HCC cells through the glycolytic bypass. We also presented miRNA-30b-5p/MINPP1 as a novel biomarker for HBV-positive HCC early diagnosis and a potential pharmaceutical target for antitumor therapy.