bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Value and Immunological Characteristics of a Novel RNA Binding Protein Signature in Cutaneous Melanoma
Authors: Tian Jun , Ma Chongzhi , Yang Li , Sun Yang , Zhang Yuan 
Published: September 2021

BackgroundThe existing studies indicate that RNA binding proteins (RBPs) are closely correlated with the genesis and development of cancers. However, the role of RBPs in cutaneous melanoma remains largely unknown. Therefore, the present study aims to establish a reliable prognostic signature based on RBPs to distinguish cutaneous melanoma patients with different prognoses and investigate the immune infiltration of patients.MethodsAfter screening RBPs from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were then used to establish a prediction model. The relationship between the signature and the abundance of immune cell types, the tumor microenvironment (TME), immune-related pathways, and immune checkpoints were also analyzed.ResultsIn total, 7 RBPs were selected to establish the prognostic signature. Patients categorized as a high-risk group demonstrated worse overall survival (OS) rates compared to those of patients categorized as a low-risk group. The signature was validated in an independent external cohort and indicated a promising prognostic ability. Further analysis indicated that the signature wasan independent prognostic indicator in cutaneous melanoma. A nomogram combining risk score and clinicopathological features was then established to evaluate the 3- and 5-year OS in cutaneous melanoma patients. Analyses of immune infiltrating, the TME, immune checkpoint, and drug susceptibility revealed significant differences between the two groups. GSEA analysis revealed that basal cell carcinoma, notch signaling pathway, melanogenesis pathways were enriched in the high-risk group, resulting in poor OS.ConclusionWe established and validated a robust 7-RBP signature that could be a potential biomarker to predict the prognosis and immunotherapy response of cutaneous melanoma patients, which provides new insights into cutaneous melanoma immunotherapeutic strategies.
Strengthening Health Systems in Humanitarian Settings: Multi-Stakeholder Insights on Contraception and Postabortion Care Programs in the Democratic Republic of Congo and Somalia
Authors: Tran Nguyen Toan , Meyers Janet , Malilo Bibiche , Chabo Julien , Muselemu Jean-Baptiste , Riziki Bienvenu , Libonga Patrick , Shire Abdikani , Had Hussein , Ali Mohamed , Arab Mohamed Abdi , Da'ar Jama Mohamed , Kahow Mohamed Hussein , Adive Joseph Ege , Gebru Binyam , Monaghan Emily , Morris Catherine N. , Gallagher Meghan , Jouanicot Virginie , Pougnier Natacha , Amsalu Ribka 
Published: September 2021

Background: In humanitarian settings, strengthening health systems while responding to the health needs of crisis-affected populations is challenging and marked with evidence gaps. Drawing from a decade of family planning and postabortion care programming in humanitarian settings, this paper aims to identify strategic components that contribute to health system strengthening in such contexts.Materials and Methods: A diverse range of key informants from North Kivu (Democratic Republic of Congo, DRC) and Puntland (Somalia), including female and male community members, adolescents and adults, healthcare providers, government and community leaders, participated in qualitative interviews, which applied the World Health Organization health system building blocks framework. Data were thematically analyzed according to this framework.Results: Findings from the focus group discussions (11 in DRC, 7 in Somalia) and key informant interviews (seven in DRC, four in Somalia) involving in total 54 female and 72 male participants across both countries indicate that health programs in humanitarian settings, such as Save the Children's initiative on family planning and postabortion care, could contribute to strengthening health systems by positively influencing national policies and guidance, strengthening local coordination mechanisms, capacitating the healthcare workforce with competency-based training and supportive supervision (benefiting facilities supported by the project and beyond), developing the capacity of Ministry of Health staff in the effective management of the supply chain, actively and creatively mobilizing the community to raise awareness and create demand, and providing quality and affordable services. Financial sustainability is challenged by the chronically limited healthcare expenditure experienced in both humanitarian contexts.Conclusions: In humanitarian settings, carefully designed healthcare interventions, such as those that address the family planning and postabortion care needs of crisis-affected populations, have the potential not only to increase access to essential services but also contribute to strengthening several components of the health system while increasing the government capacity, ownership, and accountability.
Zebrafish BID Exerts an Antibacterial Role by Negatively Regulating p53, but in a Caspase-8-Independent Manner
Authors: Qi Zhitao , Yan Dong , Cao Lu , Xu Yang , Chang Mingxian 
Published: September 2021

Bid (BH3-interacting domain death agonist), a member of the Bcl-2 family, plays a crucial role in the initiation of apoptosis. Independent of its apoptotic function, Bid is also involved in the regulation of inflammation and innate immunity. However, the role of Bid during bacterial pathogen infection remains unclear. In the present study, Bid of zebrafish (Dario rerio) was cloned and its functions during Edwardsiella ictaluri infection were investigated. Zebrafish Bid enhances the apoptosis rate of Epithelioma papulosum cyprini (EPC) cells following E. ictaluri infection. Importantly, in vitro and in vivo bacterial invasion assays showed that overexpressed Bid could significantly inhibit the invasion and proliferation of E. ictaluri. Real-time qPCR analysis revealed that p53 gene expression was downregulated in embryos microinjected with Bid-FLAG. Further, in vitro and in vivo bacterial invasion assays showed that overexpressed p53 increased the invasion and proliferation of E. ictaluri. Moreover, the invasion and proliferation of E. ictaluri were inhibited when co-overexpressing Bid and p53 in vivo and in vitro. Further, the numbers of E. ictaluri in larvae treated with Z-IETD-FMK (caspase-8 inhibitor) were higher than those of larvae without Z-IETD-FMK treatment, while the number of E. ictaluri in larvae microinjected with bid-Flag decreased significantly, even if the larvae were treated in advance with Z-IETD-FMK. Collectively, our study demonstrated a novel antibacterial activity of fish Bid, providing evidence for understanding the function of apoptosis associated gene in pathogen infection.
Common Transcriptomic Effects of Abatacept and Other DMARDs on Rheumatoid Arthritis Synovial Tissue
Authors: Triaille Clement , Durez Patrick , Sokolova Tatiana , Tilman Gaëlle , Méric de Bellefon Laurent , Galant Christine , Coulie Pierre , Lauwerys Bernard R. , Limaye Nisha 
Published: September 2021

ObjectivesOur goal was to assess for the histological and transcriptomic effects of abatacept on RA synovia, and to compare them with previously published data from four other DMARDs: tocilizumab, rituximab, methotrexate, and adalimumab.MethodsSynovial tissue was obtained using ultrasound-guided biopsy from affected joints of 14 patients, before and 16 weeks after treatment with subcutaneous abatacept 125 mg weekly. Paraffin-sections were stained and scored for CD3+, CD20+, and CD68+ cell infiltration. Transcriptional profiling was performed using GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix) and analyzed on Genespring GX (Agilent). Pathway analyses were performed on Genespring GX, Metascape, and EnrichR.ResultsGene expression analysis identified 304 transcripts modulated by abatacept in synovial tissue. Downregulated genes were significantly enriched for immune processes, strongly overlapping with our findings on other therapies. Data were pooled across these studies, revealing that genes downregulated by DMARDs are significantly enriched for both T-cell and myeloid leukocyte activation pathways. Interestingly, DMARDs seem to have coordinate effects on the two pathways, with a stronger impact in good responders to therapy as compared to moderate and non-responders.ConclusionWe provide evidence that the effects of five DMARDs on the RA synovium culminate in the same pathways. This confirms previous studies suggesting the existence of common mediators downstream of DMARDs, independent of their primary targets.
Varicocele-Mediated Male Infertility: From the Perspective of Testicular Immunity and Inflammation
Authors: Fang Yiwei , Su Yufang , Xu Jia , Hu Zhiyong , Zhao Kai , Liu Chunyan , Zhang Huiping 
Published: September 2021

BackgroundVaricocele (VC) is present in 35 - 40% of men with infertility. However, current surgical and antioxidant treatments are not completely effective. In addition to oxidative stress, it is likely that other factors such as testicular immune microenvironment disorder contribute to irreversible testicular. Evidence suggests that VC is associated with anti-sperm antibodies (ASAs), spermatogenesis and testosterone secretion abnormalities, and testicular cytokine production. Moreover, inhibition of inflammation can alleviate VC-mediated pathogenesis. The normal function of the testis depends on its immune tolerance mechanism. Testicular immune regulation is complex, and many infectious or non-infectious diseases may damage this precision system.ResultsThe testicular immune microenvironment is composed of common immune cells and other cells involved in testicular immunity. The former includes testicular macrophages, T cells, dendritic cells (DCs), and mast cells, whereas the latter include Leydig cells and Sertoli cells (SCs). In animal models and in patients with VC, most studies have revealed an abnormal increase in the levels of ASAs and pro-inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha in the seminal plasma, testicular tissue, and even peripheral blood. It is also involved in the activation of potential inflammatory pathways, such as the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing (NLRP)-3 pathway. Finally, the development of VC-mediated infertility (VMI) may be facilitated by abnormal permeability of proteins, such as claudin-11, that constitute the blood-testis barrier (BTB).ConclusionsThe testicular immune response, including the production of ASAs and inflammatory factors, activation of inflammatory pathways, and destruction of the BTB may be involved in the pathogenesis of VMI it is necessary to further explore how patient outcomes can be improved through immunotherapy.
Comparison of Outcomes of Kidney Transplantation From Extremely Low Body Weight ≤5kg Versus Larger Body Weight Pediatric Donors
Authors: Peng Jiawei , Dai Helong , Zhang Hedong , Yu Shaojie , Xie Xubiao , Peng Fenghua , Lan Gongbin , Hu Shanbiao , Wang Yu , Tang Xiaotian , Guo Yong , Gao Chen , Fang Chunhua , Nie Manhua , Yuan Xiaoqiong , Zhong Mingda , Tang Zhouqi , Li Tengfang , Sun Siyu , Yao Hengchang , Hou Jianfei , Huang Ruixue , Peng Longkai 
Published: September 2021

BackgroundKidney transplantation from donors who weigh ≤5 kg is performed at only a few transplant centers owing to the high complication and low graft survival rates associated with this approach.MethodsWe retrospectively compared the results of kidney transplantation at our center between January 2015 and December 2019 based on the following pediatric donor criteria: donor body weight ≤5 kg (n=32), 5 kg&lt; donor weight ≤20 kg (n=143), and donor weight &gt;20 kg (n=110). We also perform subgroup analysis of kidney transplantation outcomes from ≤5 kg donors, using conventional (dual separate and classic en-bloc KTx)/novel (en-bloc KTx with outflow tract) surgical methods and allocating to adult/pediatric recipients.ResultsThe death-censored graft survival rates from extremely low body weight ≤5kg at 1 month, and 1, 3, and 5 years were 90.6%, 80.9%, 77.5%, and 73.9%, respectively, which were significantly lower than that from larger body weight pediatric donors. However, the 3-, and 5-year post-transplantation eGFRs were not significantly different between the pediatric and adult recipient group. The thrombosis (18.8%) and urinary leakage (18.8%) rates were significantly higher in the donor weight ≤5 kg group. Compared with 5 kg&lt; donor weight ≤20 kg group, donor weight ≤5kg group was at elevated risk of graft loss due to thrombosis (OR: 13.4) and acute rejection (OR: 6.7). No significant difference on the outcomes of extremely low body weight donor kidney transplantation was observed between adults and pediatric recipients. Urinary leakage rate is significantly lower in the novel operation (8.7%) than in the conventional operation group (44.4%).ConclusionsAlthough the outcomes of donor body weight ≤5kg kidney transplantation is inferior to that from donors with large body weight, it can be improved through technical improvement. Donors with body weight ≤5 kg can be considered as an useful source to expand the donor pool.
Dialyzer Classification and Mortality in Hemodialysis Patients: A 3-Year Nationwide Cohort Study
Authors: Abe Masanori , Masakane Ikuto , Wada Atsushi , Nakai Shigeru , Nitta Kosaku , Nakamoto Hidetomo 
Published: September 2021

Background: Dialyzers are classified as low-flux, high-flux, and protein-leaking membrane dialyzers internationally and as types I, II, III, IV, and V based on β2-microglobulin clearance rate in Japan. Type I dialyzers correspond to low-flux membrane dialyzers, types II and III to high-flux membrane dialyzers, and types IV and V to protein-leaking membrane dialyzers. Here we aimed to clarify the association of dialyzer type with mortality.Methods: This nationwide retrospective cohort study analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry from 2010 to 2013. We enrolled 238,321 patients on hemodialysis who were divided into low-flux, high-flux, and protein-leaking groups in the international classification and into type I to V groups in the Japanese classification. We assessed the associations of each group with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis.Results: By the end of 2013, 55,308 prevalent dialysis patients (23.2%) had died. In the international classification subgroup analysis, the hazard ratio (95% confidence interval) was significantly higher in the low-flux group [1.12 (1.03–1.22), P = 0.009] and significantly lower in the protein-leaking group [0.95 (0.92–0.98), P = 0.006] compared with the high-flux group after adjustment for all confounders. In the Japanese classification subgroup analysis, the hazard ratios were significantly higher for types I [1.10 (1.02–1.19), P = 0.015] and II [1.10 (1.02–1.39), P = 0.014] but significantly lower for type V [0.91 (0.88–0.94), P &lt; 0.0001] compared with type IV after adjustment for all confounders. These significant findings persisted after propensity score matching under both classifications.Conclusions: Hemodialysis using protein-leaking dialyzers might reduce mortality rates. Furthermore, type V dialyzers are superior to type IV dialyzers in hemodialysis patients.
Evaluation of the Good Review Practices of Countries Participating in the Southern African Development Community: Alignment and Strategies for Moving Forward
Authors: Sithole Tariro , Mahlangu Gugu , Capote Velma , Sitoie Tania , Shifotoka Saren , Gaeseb Johannes , Padayachee Silverani , Sehloho Tohlang , Khea Akida , Fimbo Adam , Munkombwe Zuma , Mwale Bernice , Salek Sam , Walker Stuart 
Published: September 2021

Introduction: National medicines regulatory agencies are faced with challenges including limited resources and technical capacity, resulting in countries collaborating and sharing resources to improve efficiency of the review process to facilitate access to quality-assured medicines by their populations. One such collaboration is the Southern African Development Community (SADC) medicines registration collaborative initiative, ZaZiBoNa. Countries participate in the initiative by contributing to regulatory reviews and good manufacturing practices inspections. The aim of this study was to review and compare the registration processes of regulatory authorities of Mozambique, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe to identify strategies for better alignment.Methods: A senior member of the division responsible for issuing marketing authorisations completed an established and validated questionnaire, which standardises the review process, allowing key milestones, activities and practices of the six regulatory authorities to be identified and compared. The completed questionnaires were validated by the heads of the respective agencies.Results: The six countries vary in population and in the size of their respective regulatory agency and the resources allocated to regulatory reviews. The review processes of the six agencies were similar; however, differences were noted in the milestones recorded; for example, two of the countries did not record the start of the scientific assessment. Additionally, decisions for marketing authorisation were made by an expert committee in four of the countries and by the head of the agency and the Minister of Health in two countries. All six agencies implemented the majority of good review practices; however, the need for improvement in the areas of transparency and communication and quality decision making practices was a common finding for all six countries.Conclusions: Participation in the ZaZiBoNa initiative has improved the way in which the six agencies perform regulatory reviews in their countries, highlighting the realisation of one of the key objectives of the initiative, which was building the expert capacity of member countries. Other agencies in the SADC region and beyond can use the results of this study to identify best practices, which in turn, could improve their regulatory performance.
Respiratory Microbiota Profiles Associated With the Progression From Airway Inflammation to Remodeling in Mice With OVA-Induced Asthma
Authors: Zheng Jun , Wu Qian , Zou Ya , Wang Meifen , He Li , Guo Sheng 
Published: September 2021

BackgroundThe dysbiosis of respiratory microbiota plays an important role in asthma development. However, there is limited information on the changes in the respiratory microbiota and how these affect the host during the progression from acute allergic inflammation to airway remodeling in asthma.ObjectiveAn ovalbumin (OVA)-induced mouse model of chronic asthma was established to explore the dynamic changes in the respiratory microbiota in the different stages of asthma and their association with chronic asthma progression.MethodsHematoxylin and eosin (H&amp;E), periodic acid-schiff (PAS), and Masson staining were performed to observe the pathological changes in the lung tissues of asthmatic mice. The respiratory microbiota was analyzed using 16S rRNA gene sequencing followed by taxonomical analysis. The cytokine levels in bronchoalveolar lavage fluid (BALF) specimens were measured. The matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF-A) expression levels in lung tissues were measured to detect airway remodeling in OVA-challenged mice.ResultsAcute allergic inflammation was the major manifestation at weeks 1 and 2 after OVA atomization stimulation, whereas at week 6 after the stimulation, airway remodeling was the most prominent observation. In the acute inflammatory stage, Pseudomonas was more abundant, whereas Staphylococcus and Cupriavidus were more abundant at the airway remodeling stage. The microbial compositions of the upper and lower respiratory tracts were similar. However, the dominant respiratory microbiota in the acute inflammatory and airway remodeling phases were different. Metagenomic functional prediction showed that the pathways significantly upregulated in the acute inflammatory phase and airway remodeling phase were different. The cytokine levels in BALF and the expression patterns of proteins associated with airway remodeling in the lung tissue were consistent with the metagenomic function results.ConclusionThe dynamic changes in respiratory microbiota are closely associated with the progression of chronic asthma. Metagenomic functional prediction indicated the changes associated with acute allergic inflammation and airway remodeling.
Prognostic Immunity and Therapeutic Sensitivity Analyses Based on Differential Genomic Instability-Associated LncRNAs in Left- and Right-Sided Colon Adenocarcinoma
Authors: Guo Jun-Nan , Xia Tian-Yi , Deng Shen-Hui , Xue Wei-Nan , Cui Bin-Bin , Liu Yan-Long 
Published: September 2021

Background: The purpose of our study was to develop a prognostic risk model based on differential genomic instability-associated (DGIA) long non-coding RNAs (lncRNAs) of left-sided and right-sided colon cancers (LCCs and RCCs); therefore, the prognostic key lncRNAs could be identified.Methods: We adopted two independent gene datasets, corresponding somatic mutation and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Identification of differential DGIA lncRNAs from LCCs and RCCs was conducted with the appliance of “Limma” analysis. Then, we screened out key lncRNAs based on univariate and multivariate Cox proportional hazard regression analysis. Meanwhile, DGIA lncRNAs related prognostic model (DRPM) was established. We employed the DRPM in the model group and internal verification group from TCGA for the purpose of risk grouping and accuracy verification of DRPM. We also verified the accuracy of key lncRNAs with GEO data. Finally, the differences of immune infiltration, functional pathways, and therapeutic sensitivities were analyzed within different risk groups.Results: A total of 123 DGIA lncRNAs were screened out by differential expression analysis. We obtained six DGIA lncRNAs by the construction of DRPM, including AC004009.1, AP003555.2, BOLA3-AS1, NKILA, LINC00543, and UCA1. After the risk grouping by these DGIA lncRNAs, we found the prognosis of the high-risk group (HRG) was significantly worse than that in the low-risk group (LRG) (all p &lt; 0.05). In all TCGA samples and model group, the expression of CD8+ T cells in HRG was lower than that in LRG (all p &lt; 0.05). The functional analysis indicated that there was significant upregulation with regard to pathways related to both genetic instability and immunity in LRG, including cytosolic DNA sensing pathway, response to double-strand RNA, RIG-Ⅰ like receptor signaling pathway, and Toll-like receptor signaling pathway. Finally, we analyzed the difference and significance of key DGIA lncRNAs and risk groups in multiple therapeutic sensitivities.Conclusion: Through the analysis of the DGIA lncRNAs between LCCs and RCCs, we identified six key DGIA lncRNAs. They can not only predict the prognostic risk of patients but also serve as biomarkers for evaluating the differences of genetic instability, immune infiltration, and therapeutic sensitivity.