bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing bladder cancer management: development of a prognostic model and personalized therapy
Authors: Huang Xiang , Du Guotu , Yang Ying , Su Peng , Chen Shicheng , Cai Chongjiong , Huang Tianyu , Zeng Yu , Tao Yonggang , Tian Demei , Zhang Neng 
Published: July 2024

BackgroundBladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score.MethodsSingle-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses.ResultsSix molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups.ConclusionsThe study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.
Human liver derived mesenchymal stromal cells ameliorate murine ischemia-induced inflammation through macrophage polarization
Authors: Liang Yun , Ozdogan Elif , Hansen Michael J. , Tang Hui , Saadiq Ishran , Jordan Kyra L. , Krier James D. , Gandhi Deep B. , Grande Joseph P. , Lerman Lilach O. , Taner Timucin 
Published: July 2024

IntroductionThe immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro.MethodTo test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses.ResultsThe stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes.DiscussionThese in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.
Effects of Bacillus subtilis-fermented soybean meal replacing fish meal on antioxidant activity, immunity, endoplasmic reticulum stress and hepatopancreas histology in Pacific white shrimp (Litopenaeus vannamei)
Authors: Chen Songming , Dai Jieyu , Chen Yan , Chen Qiang , Dong Fen , Wang Congcong , Sun Yulong , Wang Jiteng , Han Tao 
Published: July 2024

IntroductionScreening excellent bacterial strains for fermentation is the key to improving the nutritional value and bioavailability of soybean meal (SBM). This study investigated the application of Bacillus subtilis-fermented soybean meal (FSBM) on the feed of Pacific white shrimp (Litopenaeus vannamei).MethodsFSBM was used to replace 0%, 25%, 50%, 75%, and 100% fish meal, and the feeding trial was lasted for 8 weeks (initial weight: 0.9 g). Results and discussionThe amino acid profile in the whole shrimp body was tested. FSBM substitution only significantly reduced the content lysine in whole shrimp body, but increased the content of arginine. Fatty acid data showed that the content of n-6 PUFAs in whole shrimp was significantly increased by FSBM substitution. In muscle, FSBM substitution significantly reduced the content of MUFAs, but increased the content of PUFAs including C18:3n-3, C18:2n-6 and C20:4n-6. No hepatopancreas structure modifications appeared in the 25% group compared with the control group. Subsequently, we investigated the response patterns of different organs to FSBM substitution from antioxidant, endoplasmic reticulum stress and immunity. A high proportion of FSBM significantly reduced the content of GSH in hemolymph and hepatopancreas, while increased the mRNA expression of cat. FSBM substitution did not affect the activities of antioxidant enzymes in the intestine. However, the mRNA expression level of hsp70 in the intestine was significantly reduced by FSBM. In terms of immunity, the mRNA expression levels of lgbp and penaeidin in the hepatopancreas showed a significant linear increase trend. In muscle, high proportion of FSBM significantly increased the mRNA expression of imd. FSBM substitution did not significantly affect the expression of immune genes in the intestine. In terms of endoplasmic reticulum stress, FSBM substitution significantly increased the mRNA expression of eif2α in the hepatopancreas. In muscle, FSBM substitution inhibited the mRNA expression of bip. In the intestine, FSBM replacing 75% of fish meal significantly increased the mRNA expression of bip and ire1. In summary, this study indicated that when the fish meal content account for 40% in diets (dry weight), the screened Bacillus subtilis-FSBM can replace 25% of fish meal protein without reducing the antioxidant and immune abilities of shrimp.
Exploring constructions of female surgeons’ intersecting identities and their impacts: a qualitative interview study with clinicians and patients in Ireland and Scotland
Authors: Offiah Gozie , Cable Stuart , Schofield Susie , Rees Charlotte E. 
Published: July 2024

IntroductionWhile many studies have explored surgeons’ personal and professional identities separately, our study is the first to examine intersecting female surgical identities. We explore intersecting surgical identities constructed by self and others (colleagues and patients) within two healthcare systems and their perceived impacts answering the research question: How do female surgeons’ constructed identities intersect, and what influences do those intersections have on their surgical lives?MethodsWe employed qualitative methodology drawing on semi-structured biographical narrative interviews underpinned by social constructionism. We employed intersectionality theory as an analytical lens. We adopted maximum variation sampling to identify diverse participants, including 38 surgeons (29 female; 9 male), 9 non-surgical colleagues (8 female, 1 male), and 13 patients of female surgeons (7 female, 6 male). Our 29 female surgeons also included six who had transitioned out of surgery. We analyzed the dataset using a five-step Framework Analysis approach. We captured talkaboutidentities, as well as identity talk (constructions of identity through participants’ talk).FindingsMultiple intersecting personal (not just gender) and professional identities were constructed and reported to have multiple impacts on female surgeons’ lives (including their education, training, and success). We present intersecting identities and their impacts relating to gender through four primary intersections: (a) gender + ethnic identities; (b) gender + parenthood identities; (c) gender + age identities; and (d) gender + professional identities (namely carer, competent, mentor/mentee, role model and leader). Our findings particularly highlight the challenges experienced by female surgeons of color, who are mothers, who are younger and/or who are leaders, illustrating diversity in women’s experiences beyond that of gender alone. Finally, we found unexpected insights into male surgeons and fatherhood.DiscussionIntersectionality theory offered a novel analytical lens to extend existing knowledge on female surgical identities. Further research is warranted exploring intersecting identities of female surgeons of color, younger female surgeons, and male surgeons who are fathers, as well as identities unexplored in this study (e.g., diverse sexualities). We need to raise awareness of intersecting identities and their impacts in surgery, as well as providing training, allyship, and policy revision that is sensitive to intersectionality.
Correlation between Tregs and ICOS-induced M2 macrophages polarization in colorectal cancer progression
Authors: Xu Jiaxin , Gao Yu , Ding Yuting , Feng Yunpeng , Chen Jie , Zhang Shenshen , Song Xiaoyu , Qiao Shifeng 
Published: July 2024

ObjectiveTo explore the mechanism by which Tregs promote the progression of colorectal cancer by inducing tumor-associated macrophages to polarize into M2 type via ICOS.MethodsPostoperative pathological tissues and clinical pathological data of 268 colorectal cancer patients who underwent initial surgery were collected. Immunohistochemistry (IHC) was used to detect the expression levels of ICOS, CD163 (a marker for M2 macrophages), and Foxp3 (a marker for Tregs) in cancerous, adjacent non-tumorous, and normal tissues. The relationship of ICOS, M2 macrophages, and Tregs in CRC with clinical pathological characteristics and pre-surgical tumor markers (such as CEA and CA199) was explored.ResultsThe expression levels of M2 macrophages and Tregs increased with tumor progression, while ICOS expression showed a decreasing trend. Compared to adjacent and normal tissues, the expression levels of ICOS, M2 macrophages, and Tregs were higher in CRC tissues. The expression levels of M2 macrophages and Tregs were significantly positively correlated with tumor markers, while ICOS expression was significantly negatively correlated.ConclusionTumor-associated m2 macrophages induced by Tregs and ICOS participate in the dynamic balance of the colorectal cancer tumor microenvironment, and their interaction affects colorectal carcinogenesis and progression. High levels of ICOS are associated with better long-term survival rates.
Adipose microenvironment promotes hypersialylation of ovarian cancer cells
Authors: Fox Alexandra , Leonard Garry D. , Adzibolosu Nicholas , Wong Terrence , Tedja Roslyn , Sharma Sapna , Gogoi Radhika , Morris Robert , Mor Gil , Fehl Charlie , Alvero Ayesha B. 
Published: July 2024

IntroductionOvarian and other peritoneal cancers have a strong tendency to metastasize into the surrounding adipose tissue. This study describes an effect of the adipose microenvironment on upregulation of sialic acid-containing glycans in ovarian cancer (OC). Heterogeneous populations of glycosylated OC tumors converged to a highly sialylated cell state that regulates tumorigenesis in an immune-dependent manner.MethodsWe modeled the adipose microenvironment by conditioning growth media with human patient-derived adipose tissue. OC cell lines grown in the presence vs. absence of adipose conditioned media (ACM) were characterized by transcriptomics, western blotting, and chemical biology glycan labeling methods. Fluorescence-activated cell sorting was used to separate adipose-driven upregulation of hypersialylated (“SNA-high”) vs. hyposialylated (“SNA-low”) OC subpopulations. The two subpopulations were characterized by further transcriptomic and quantitative polymerase chain reaction analyses, then injected into a syngeneic mouse model. Immune system involvement was implicated using wild type and athymic nude mice with a primary endpoint of overall survival.ResultsAdipose conditioning resulted in upregulation of sialyltransferases ST3GAL1, ST6GAL1, ST6GALNAC3, and ST8Sia1. In culture, OC cells displayed two distinct sialylated subpopulations that were stable for up to 9 passages, suggesting inherent heterogeneity in sialylation that is maintained throughout cell division and media changes. OC tumors that implanted in the omental adipose tissue exclusively reprogrammed to the highly sialylated subpopulation. In wild type C57BL/6 mice, only the hypersialylated SNA-high subpopulation implanted in the adipose, whereas the hyposialylated SNA-low subpopulation failed to be tumorigenic (p=0.023, n=5). In the single case where SNA-low established a tumor, post-mortem analysis revealed reprogramming of the tumor to the SNA-high state in vivo. In athymic nude mice, both subpopulations rapidly formed tumors, implicating a role of the adaptive immune system.ConclusionsThese findings suggest a model of glycan-dependent tumor evolution wherein the adipose microenvironment reprograms OC to a tumorigenic state that resists the adaptive immune system. Mechanistically, adipose factors upregulate sialyltransferases. To our knowledge, this is the first demonstration of the effect of adipose microenvironment on OC tumor sialylation. Our results set the stage for translational applications targeting sialic acid pathways in OC and other peritoneal cancer tumorigenesis and metastasis.
Analyzing the defense response mechanism of Atractylodes macrocephala to Fusarium oxysporum through small RNA and degradome sequencing
Authors: Fan Sen , Tang Yunjia , Zhu Na , Meng Qingling , Zhou Yanguang , Zhao Yujin , Xu Jingyan , Gu Chenxian , Dai Shijie , Zhu Bo , Yuan Xiaofeng 
Published: July 2024

IntroductionFusarium oxysporum is a significant soil-borne fungal pathogen that affects over 100 plant species, including crucial crops like tomatoes, bananas, cotton, cucumbers, and watermelons, leading to wilting, yellowing, growth inhibition, and ultimately plant death. The root rot disease of A. macrocephala, caused by F. oxysporum, is one of the most serious diseases in continuous cropping, which seriously affects its sustainable development.MethodsIn this study, we explored the interaction between A. macrocephala and F. oxysporum through integrated small RNA (sRNA) and degradome sequencing to uncover the microRNA (miRNA)–mediated defense mechanisms.ResultsWe identified colonization of F. oxysporum in A. macrocephala roots on day 6. Nine sRNA samples were sequenced to examine the dynamic changes in miRNA expression in A. macrocephala infected by F. oxysporum at 0, 6, and 12 days after inoculation. Furthermore, we using degradome sequencing and quantitative real-time PCR (qRT-PCR), validated four miRNA/target regulatory units involved in A. macrocephala–F. oxysporum interactions.DiscussionThis study provides new insights into the molecular mechanisms underlying A. macrocephala's early defense against F. oxysporum infection, suggesting directions for enhancing resistance against this pathogen.
Machine learning-based analysis and prediction of meteorological factors and urban heatstroke diseases
Authors: Xu Hui , Guo Shufang , Shi Xiaojun , Wu Yanzhen , Pan Junyi , Gao Han , Tang Yan , Han Aiqing 
Published: July 2024

IntroductionHeatstroke is a serious clinical condition caused by exposure to high temperature and high humidity environment, which leads to a rapid increase of the core temperature of the body to more than 40°C, accompanied by skin burning, consciousness disorders and other organ system damage. This study aims to analyze the effect of meteorological factors on the incidence of heatstroke using machine learning, and to construct a heatstroke forecasting model to provide reference for heatstroke prevention.MethodsThe data of heatstroke incidence and meteorological factors in a city in South China from May to September 2014–2019 were analyzed in this study. The lagged effect of meteorological factors on heatstroke incidence was analyzed based on the distributed lag non-linear model, and the prediction model was constructed by using regression decision tree, random forest, gradient boosting trees, linear SVRs, LSTMs, and ARIMA algorithm.ResultsThe cumulative lagged effect found that heat index, dew-point temperature, daily maximum temperature and relative humidity had the greatest influence on heatstroke. When the heat index, dew-point temperature, and daily maximum temperature exceeded certain thresholds, the risk of heatstroke was significantly increased on the same day and within the following 5 days. The lagged effect of relative humidity on the occurrence of heatstroke was different with the change of relative humidity, and both excessively high and low environmental humidity levels exhibited a longer lagged effect on the occurrence of heatstroke. With regard to the prediction model, random forest model had the best performance of 5.28 on RMSE and dropped to 3.77 after being adjusted.DiscussionThe incidence of heatstroke in this city is significantly correlated with heat index, heatwave, dew-point temperature, air temperature and zhongfu, among which the heat index and dew-point temperature have a significant lagged effect on heatstroke incidence. Relevant departments need to closely monitor the data of the correlated factors, and adopt heat prevention measures before the temperature peaks, calling on citizens to reduce outdoor activities.
A rapid review of the barriers and facilitators of mental health service access among Veterans and their families
Authors: Ein Natalie , Gervasio Julia , St. Cyr Kate , Liu Jenny J. W. , Baker Clara , Nazarov Anthony , Richardson J. Don 
Published: July 2024

IntroductionTransitioning to civilian life after military service can be challenging for both Veterans and their families. Accessible mental health services are crucial during this period to provide support. The objective of this review was to conduct a rapid review to capture the barriers and identify facilitators that influence access to mental health services for Veterans and their families during the post-service transition period.MethodsThis review was conducted using the Cochrane Handbook for Systematic Reviews of Interventions as a methodological framework and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Rapid Review (PRISMA-RR).ResultsA total of 60 articles and 67 independent samples were included in the final data analyses. Across the included articles, this review identified 23 barriers and 14 facilitator themes. Issues navigating the mental health care system was identified as the main challenge among Veterans and their families, and those who received support navigating the system identified this as a significant facilitator. Applying the Theoretical Domains Framework, most of the identified barriers and facilitators were categorized into environmental context and resources domain.DiscussionThe heterogeneity in Veterans' and Veteran families' experiences with mental health care-seeking may suggest that access to mental health care for Veterans and Veteran families cannot be solved by addressing one type of barrier alone. Instead, coordinated efforts to address prioritized systemic, logistical, social, and inter-/intrapersonal obstacles are essential for improving access and optimizing mental health care outcomes. These insights underscore the complexity of considerations for Veterans and families accessing mental health care.
Diverse PFAS produce unique transcriptomic changes linked to developmental toxicity in zebrafish
Authors: Rericha Yvonne , St. Mary Lindsey , Truong Lisa , McClure Ryan , Martin J. Kainalu , Leonard Scott W. , Thunga Preethi , Simonich Michael T. , Waters Katrina M. , Field Jennifer A. , Tanguay Robyn L. 
Published: July 2024

Per- and polyfluoroalkyl substances (PFAS) are a widespread and persistent class of contaminants posing significant environmental and human health concerns. Comprehensive understanding of the modes of action underlying toxicity among structurally diverse PFAS is mostly lacking. To address this need, we recently reported on our application of developing zebrafish to evaluate a large library of PFAS for developmental toxicity. In the present study, we prioritized 15 bioactive PFAS that induced significant morphological effects and performed RNA-sequencing to characterize early transcriptional responses at a single timepoint (48 h post fertilization) after early developmental exposures (8 h post fertilization). Internal concentrations of 5 of the 15 PFAS were measured from pooled whole fish samples across multiple timepoints between 24–120 h post fertilization, and additional temporal transcriptomics at several timepoints (48–96 h post fertilization) were conducted for Nafion byproduct 2. A broad range of differentially expressed gene counts were identified across the PFAS exposures. Most PFAS that elicited robust transcriptomic changes affected biological processes of the brain and nervous system development. While PFAS disrupted unique processes, we also found that similarities in some functional head groups of PFAS were associated with the disruption in expression of similar gene sets. Body burdens after early developmental exposures to select sulfonic acid PFAS, including Nafion byproduct 2, increased from the 24–96 h post fertilization sampling timepoints and were greater than those of sulfonamide PFAS of similar chain lengths. In parallel, the Nafion byproduct 2-induced transcriptional responses increased between 48 and 96 h post fertilization. PFAS characteristics based on toxicity, transcriptomic effects, and modes of action will contribute to further prioritization of PFAS structures for testing and informed hazard assessment.