bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients
Authors: Lupieri Adrien , Nagata Yasufumi , Passos Livia S. A. , Beker-Greene Dakota , Kirkwood Katherine A. , Wylie-Sears Jill , Alvandi Zahra , Higashi Hideyuki , Hung Judy W. , Singh Sasha A. , Bischoff Joyce , Levine Robert A. , Aikawa Elena 
Published: June 2023

Background: Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Nevertheless, little is known about how MV tissue responds to ischemic heart changes in humans.Methods: MVs were obtained by the Cardiothoracic Surgical Trials Network from 17 patients with ischemic mitral regurgitation (IMR). Echo-doppler imaging assessed MV function at time of resection. Cryosections of MVs were analyzed using a multi-faceted histology and immunofluorescence examination of cell populations. MVs were further analyzed using unbiased label-free proteomics. Echo-Doppler imaging, histo-cytometry measures and proteomic analysis were then integrated.Results: MVs from patients with greater MR exhibited proteomic changes associated with proteolysis-, inflammatory- and oxidative stress-related processes compared to MVs with less MR. Cryosections of MVs from patients with IMR displayed activated valvular interstitial cells (aVICs) and double positive CD31+ αSMA+ cells, a hallmark of EndMT. Univariable and multivariable association with echocardiography measures revealed a positive correlation of MR severity with both cellular and geometric changes (e.g., aVICs, EndMT, leaflet thickness, leaflet tenting). Finally, proteomic changes associated with EndMT showed gene-ontology enrichment in vesicle-, inflammatory- and oxidative stress-related processes. This discovery approach indicated new candidate proteins associated with EndMT regulation in IMR.Conclusion: We describe an atypical cellular composition and distinctive proteome of human MVs from patients with IMR, which highlighted new candidate proteins implicated in EndMT-related processes, associated with maladaptive MV fibrotic remodeling.
Barriers, facilitators and motivators of electronic community health information system use among health workers in Ethiopia
Authors: Bogale Tariku Nigatu , Teklehaimanot Selamawit Meressa , Fufa Debela Tilahun , Enyew Daniel Berhanie , Nigusse Bedada Abebe , Dufera Kebebew Segni , Nigusie Weldeab Adane , Wolde Daka Dawit , Willems Herman Jozef , Bekele Tadesse Alemu 
Published: June 2023

BackgroundThe electronic community health information system (eCHIS) has been implemented in Ethiopia to support health services delivered by community health workers. Despite the many benefits of digitizing community health information systems, the implementation of the eCHIS is challenged by many barriers resulting in low uptake. This study assessed the barriers, facilitators, and motivators of eCHIS use among health workers with focus on health extension workers (HEWs) in Ethiopia.MethodsPhenomenological approach was used to assess the barriers, facilitators and motivators of eCHIS use in Amhara, Harari, Oromia, Sidama, South West Ethiopia and Southern Nation Nationalities and People's regions of Ethiopia. Data were collected from 15–29 May 2022. A total of 54 face-to-face in-depth interviews were conducted among HEWs, HEW supervisors, health information technicians and managers. The interviews were audiotaped using Open Data Kit, transcribed verbatim and translated into English. OpenCode 4.03 software was used for coding and categorizing the data. Thematic analysis was used to analyze the data.ResultsThe HEWs and other eCHIS users reported lack of infrastructure and resources; poor quality of training, follow-up, and supervision; parallel recording using the manual and electronic system; and HEWs' workload as barriers hindering eCHIS use. Data quality, retrievability, and traceability; tablet portability; encouragement from supervisors; and positive image in the community resulting from HEWs using tablets in their routine activities were the main facilitators of eCHIS use.ConclusionThe study identified various barriers that adversely affect the use of eCHIS. An integrated and coordinated approach to eCHIS implementation that encompasses removing the barriers, and reinforcing facilitators is required.
Machine learning immune-related gene based on KLRB1 model for predicting the prognosis and immune cell infiltration of breast cancer
Authors: Huang Guo , Xiao Shuhui , Jiang Zhan , Zhou Xue , Chen Li , Long Lin , Zhang Sheng , Xu Ke , Chen Juan , Jiang Bin 
Published: June 2023

ObjectiveBreast cancer is a prevalent malignancy that predominantly affects women. The development and progression of this disease are strongly influenced by the tumor microenvironment and immune infiltration. Therefore, investigating immune-related genes associated with breast cancer prognosis is a crucial approach to enhance the diagnosis and treatment of breast cancer.MethodsWe analyzed data from the TCGA database to determine the proportion of invasive immune cells, immune components, and matrix components in breast cancer patients. Using this data, we constructed a risk prediction model to predict breast cancer prognosis and evaluated the correlation between KLRB1 expression and clinicopathological features and immune invasion. Additionally, we investigated the role of KLRB1 in breast cancer using various experimental techniques including real-time quantitative PCR, MTT assays, Transwell assays, Wound healing assays, EdU assays, and flow cytometry.ResultsThe functional enrichment analysis of immune and stromal components in breast cancer revealed that T cell activation, differentiation, and regulation, as well as lymphocyte differentiation and regulation, play critical roles in determining the status of the tumor microenvironment. These DEGs are therefore considered key factors affecting TME status. Additionally, immune-related gene risk models were constructed and found to be effective predictors of breast cancer prognosis. Further analysis through KM survival analysis and univariate and multivariate Cox regression analysis demonstrated that KLRB1 is an independent prognostic factor for breast cancer. KLRB1 is closely associated with immunoinfiltrating cells. Finally, in vitro experiments confirmed that overexpression of KLRB1 inhibits breast cancer cell proliferation, migration, invasion, and DNA replication ability. KLRB1 was also found to inhibit the proliferation of breast cancer cells by blocking cell division in the G1/M phase.ConclusionKLRB1 may be a potential prognostic marker and therapeutic target associated with the microenzymic environment of breast cancer tumors, providing a new direction for breast cancer treatment.
The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience
Authors: Siemaszko Jagoda , Ussowicz Marek , Rybka Blanka , Ryczan-Krawczyk Renata , Kałwak Krzysztof , Bogunia-Kubik Katarzyna 
Published: June 2023

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children.Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival.Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients’ HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 &lt; p &lt; 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation.Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.
Integrated single-cell and bulk characterization of cuproptosis key regulator PDHB and association with tumor microenvironment infiltration in clear cell renal cell carcinoma
Authors: Wu Jiajin , Wang Songbo , Liu Yiyang , Zhang Tongtong , Wang Xiaoyi , Miao Chenkui 
Published: June 2023

BackgroundRenal clear cell carcinoma (ccRCC) is one of the most prevalent cancers worldwide. Accumulating evidence revealed that copper-induced cell death played a vital role in various tumors. However, the underlying mechanism of cuproptosis with molecular heterogeneity and tumor microenvironment (TME) in ccRCC remains to be elucidated. The present study aimed to discover the biological function of cuproptosis regulators with the potential to guide clinical therapy.MethodsUsing Single-cell RNA-seq, bulk transcriptome and other multi-omics datasets, we identify essential cuproptosis-related hub gene PDHB for further study. The dysregulation of PDHB in ccRCC was characterized, together with survival outcomes, pathway enrichment and immune infiltration among tumor microenvironments. The functional significance and clinical association of PDHB was validated with loss of function experiments and surgical removal specimens.ResultsPDHB mRNA and protein expression level was significantly downregulated in ccRCC tissues compared with normal and paired normal tissues. Clinicopathological parameters and tissue microarray (TMA) indicated that PDHB was identified as a prognostic factor for survival outcomes among ccRCC patients. Additionally, low PDHB was negatively correlated with Treg cells, indicating an immunosuppressive microenvironment. Mechanistically, knockdown PDHB appeared to promote the RCC cells proliferation, migration, and invasion potentials. Subsequent studies showed that copper-induced cell death activation could overcome sunitinib resistance in RCC cells.ConclusionThis research illustrated a cuproptosis-related hub gene PDHB which could serve as a potential prognostic marker and provide therapeutic benefits for clinical treatment of ccRCC patients.
Monocyte at diagnosis as a prognosis biomarker in tuberculosis patients with anemia
Authors: Luo Mengxing , Zou Xin , Zeng Qibing , Wu Yaxing , Yang Hua , Qin Lianhua , Zheng Ruijuan , Yu Fangyou , Hu Yang , Liu Zhonghua 
Published: June 2023

BackgroundAnemia leads to a lower cure rate and poor prognosis in tuberculosis patients. Effective predictors for the prognosis of tuberculosis with anemia (A-TB) are urgently needed. Monocyte has been proven to be a prognostic biomarker of many lung diseases. Whether monocyte that the predominant innate immune cell as early defense against tuberculosis can predict A-TB is not known.MethodsData for A-TB patients with initial treatment in Shanghai Pulmonary Hospital were retrospectively collected and analyzed. Logistics regression analysis was used to study the correlation between peripheral blood cells and treatment outcomes. The receiver operating characteristic (ROC) curve was used to determine the cut-off value. We estimated a 12-month prognosis using Kaplan–Meier techniques. The Cox proportional hazards model was used for the univariate and multivariate analyses to analyze the predictors of poor prognosis of A-TB.ResultsOf 181 patients analyzed, 94 were cured and 87 non-cured. Logistic regression analysis identified monocyte as an independent immune-related risk factor for the prognosis of A-TB (OR: 7.881, 95% CI: 1.675–37.075, P = 0.009). The ROC curve analysis proved that the most discriminative cut-off value of monocyte was 0.535 × 10^9/L. K–M analysis demonstrated that the cumulative cure rates of A-TB were significantly higher in A-TB with monocyte &lt; 0.535 × 10^9/L (69.62%) than that in those with monocyte ≥ 0.535 × 10^9/L (38.24%) (Log-rank, χ2 = 16.530, P &lt; 0.0001). On univariate and multivariable analysis, monocyte was an independent predictor of poor prognosis in A-TB. Similarly, monocyte was also an independent predictor of poor pulmonary cavity closure in A-TB (HR: 3.614, 95% CI: 1.335–9.787, P = 0.011).ConclusionIn A-TB patients, elevated monocyte was associated with poor prognosis and poor cavity pulmonary closure. Monocyte may provide a simple and inexpensive prognostic biomarker in A-TB.
Sex and age differences in chronic postoperative pain among patients undergoing thoracic surgery: a retrospective cohort study
Authors: Zhao Ying , Liu Xin-Min , Zhang Lu-Yao , Li Bing , Wang Ruo-Han , Yuan Qin-Yue , Wang Shi-Chao , Zhu Hai-Peng , Zhi Hui , Zhang Jia-Qiang , Zhang Wei 
Published: June 2023

BackgroundThe effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences.MethodsThis was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up.ResultsAmong the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP.ConclusionFemales have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.
Landscape characteristics shape surface soil microbiomes in the Chihuahuan Desert
Authors: Hansen Frederick A. , James Darren K. , Anderson John P. , Meredith Christy S. , Dominguez Andrew J. , Pombubpa Nuttapon , Stajich Jason E. , Romero-Olivares Adriana L. , Salley Shawn W. , Pietrasiak Nicole 
Published: June 2023

IntroductionSoil microbial communities, including biological soil crust microbiomes, play key roles in water, carbon and nitrogen cycling, biological weathering, and other nutrient releasing processes of desert ecosystems. However, our knowledge of microbial distribution patterns and ecological drivers is still poor, especially so for the Chihuahuan Desert.MethodsThis project investigated the effects of trampling disturbance on surface soil microbiomes, explored community composition and structure, and related patterns to abiotic and biotic landscape characteristics within the Chihuahuan Desert biome. Composite soil samples were collected in disturbed and undisturbed areas of 15 long-term ecological research plots in the Jornada Basin, New Mexico. Microbial diversity of cross-domain microbial groups (total Bacteria, Cyanobacteria, Archaea, and Fungi) was obtained via DNA amplicon metabarcode sequencing. Sequence data were related to landscape characteristics including vegetation type, landforms, ecological site and state as well as soil properties including gravel content, soil texture, pH, and electrical conductivity.ResultsFilamentous Cyanobacteria dominated the photoautotrophic community while Proteobacteria and Actinobacteria dominated among the heterotrophic bacteria. Thaumarchaeota were the most abundant Archaea and drought adapted taxa in Dothideomycetes and Agaricomycetes were most abundant fungi in the soil surface microbiomes. Apart from richness within Archaea (p = 0.0124), disturbed samples did not differ from undisturbed samples with respect to alpha diversity and community composition (p ≥ 0.05), possibly due to a lack of frequent or impactful disturbance. Vegetation type and landform showed differences in richness of Bacteria, Archaea, and Cyanobacteria but not in Fungi. Richness lacked strong relationships with soil variables. Landscape features including parent material, vegetation type, landform type, and ecological sites and states, exhibited stronger influence on relative abundances and microbial community composition than on alpha diversity, especially for Cyanobacteria and Fungi. Soil texture, moisture, pH, electrical conductivity, lichen cover, and perennial plant biomass correlated strongly with microbial community gradients detected in NMDS ordinations.DiscussionOur study provides first comprehensive insights into the relationships between landscape characteristics, associated soil properties, and cross-domain soil microbiomes in the Chihuahuan Desert. Our findings will inform land management and restoration efforts and aid in the understanding of processes such as desertification and state transitioning, which represent urgent ecological and economical challenges in drylands around the world.
Phenotypic and genetic features of a novel clinically isolated rough morphotype Candida auris
Authors: Tian Sufei , Bing Jian , Chu Yunzhuo , Li Hailong , Wang Qihui , Cheng Shitong , Chen Jingjing , Shang Hong 
Published: June 2023

IntroductionCandida auris is a newly emerging pathogenic fungus of global concern and has been defined by the World Health Organization (WHO) as a member of the critical group of the most health-threatening fungi.MethodsThis study reveals and reports for the first time that a rough morphotype C. auris strain causes urinary tract infections in non-intensive care unit (ICU) inpatients. Furthermore, the morphology, the scanning electronmicroscopy (SEM), Whole-genome resequencing and RNA sequencing of C. auris possessing rough morphotype colonies compared to their smooth morphotype counterparts.ResultsThe newly identified phenotypic variation of C. auris appears round, convex, dry, and burr-like with a rough texture. SEM shows that rough type C. auris has a rough and uneven colony surface with radial wrinkles and irregular spore arrangement. Cells of the rough morphotype C. auris naturally aggregate into clusters with tight connections in the liquid, and it seems that the cell division is incomplete. A genome-wide analysis of the rough type C. auris confirmed its genetic association with the smooth type of C. auris prevalent in China (Shenyang) two years ago; however, single nucleotide polymorphism (SNP) mutations of five genes (ACE2, IFF6, RER2, UTP20, and CaO19.5847) were identified more recently. RNA-seq revealed IFF2/HYR3, DAL5, PSA31, and SIT1 were notably up-regulated, while multiple cell wall-associated genes (ALS1, MNN1, PUL1, DSE1, SCW11, PGA38, RBE1, FGR41, BGLI, GIT3, CEP3, and SAP2) were consistently down-regulated in rough morphotype C. auris.DiscussionThe rough phenotypic variation of C. auris is likely to be related to the structural and functional changes in cell wall proteins. This novel rough morphotype C. auris will provide a basis for further studies concerning the evolutionary characteristics of C. auris.
Multi-omic analysis of glycolytic signatures: exploring the predictive significance of heterogeneity and stemness in immunotherapy response and outcomes in hepatocellular carcinoma
Authors: Zhang Shiyu , Pei Yangting , Zhu Feng 
Published: June 2023

Background: Hepatocellular carcinoma (HCC) is a global health challenge with complex pathophysiology, characterized by high mortality rates and poor early detection due to significant tumor heterogeneity. Stemness significantly contributes to the heterogeneity of HCC tumors, and glycolysis is crucial for maintaining stemness. However, the predictive significance of glycolysis-related metabolic genes (GMGs) in HCC remains unknown. Therefore, this study aimed to identify critical GMGs and establish a reliable model for HCC prognosis.Methods: GMGs associated with prognosis were identified by evaluating genes with notable expression changes between HCC and normal tissues retrieved from the MsigDB database. Prognostic gene characteristics were established using univariate and multivariate Cox regression studies for prognosis prediction and risk stratification. The “CIBERSORT” and “pRRophetic” R packages were respectively used to evaluate the immunological environment and predict treatment response in HCC subtypes. The HCC stemness score was obtained using the OCLR technique. The precision of drug sensitivity prediction was evaluated using CCK-8 experiments performed on HCC cells. The miagration and invasion ability of HCC cell lines with different riskscores were assessed using Transwell and wound healing assays.Results: The risk model based on 10 gene characteristics showed high prediction accuracy as indicated by the receiver operating characteristic (ROC) curves. Moreover, the two GMG-related subgroups showed considerable variation in the risk of HCC with respect to tumor stemness, immune landscape, and prognostic stratification. The in vitro validation of the model’s ability to predict medication response further demonstrated its reliability.Conclusion: Our study highlights the importance of stemness variability and inter-individual variation in determining the HCC risk landscape. The risk model we developed provides HCC patients with a novel method for precision medicine that enables clinical doctors to customize treatment plans based on unique patient characteristics. Our findings have significant implications for tailored immunotherapy and chemotherapy methods, and may pave the way for more personalized and effective treatment strategies for HCC.