bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mid-level managers’ perspectives on implementing isoniazid preventive therapy for people living with HIV in Ugandan health districts: a qualitative study
Authors: Christian Canice , Kakande Elijah , Nahurira Violah , Akatukwasa Cecilia , Atwine Fredrick , Bakanoma Robert , Itiakorit Harriet , Owaraganise Asiphas , DiIeso William , Rast Derek , Kabami Jane , Peretz Jason Johnson , Shade Starley B. , Kamya Moses R. , Havlir Diane V. , Chamie Gabriel , Camlin Carol S. 
Published: March 2024

Abstract
Background
Isoniazid preventive therapy (IPT) works to prevent tuberculosis (TB) among people living with HIV (PLHIV), but uptake remains low in Sub-Saharan Africa. In this analysis, we sought to identify barriers mid-level managers face in scaling IPT in Uganda and the mechanisms by which the SEARCH-IPT trial intervention influenced their abilities to increase IPT uptake.

Methods
The SEARCH-IPT study was a cluster randomized trial conducted from 2017–2021. The SEARCH-IPT intervention created collaborative groups of district health managers, facilitated by local HIV and TB experts, and provided leadership and management training over 3-years to increase IPT uptake in Uganda. In this qualitative study we analyzed transcripts of annual Focus Group Discussions and Key Informant Interviews, from a subset of SEARCH-IPT participants from intervention and control groups, and participant observation field notes. We conducted the analysis using inductive and deductive coding (with a priori codes and those derived from analysis) and a framework approach for data synthesis.

Results
When discussing factors that enabled positive outcomes, intervention managers described feeling ownership over interventions, supported by the leadership and management training they received in the SEARCH-IPT study, and the importance of collaboration between districts facilitated by the intervention. In contrast, when discussing factors that impeded their ability to make changes, intervention and control managers described external funders setting agendas, lack of collaboration in meetings that operated with more of a ‘top-down’ approach, inadequate supplies and staffing, and lack of motivation among frontline providers. Intervention group managers mentioned redistribution of available stock within districts as well as between districts, reflecting efforts of the SEARCH-IPT intervention to promote between-district collaboration, whereas control group managers mentioned redistribution within their districts to maximize the use of available IPT stock.

Conclusions
In Uganda, mid-level managers’ perceptions of barriers to scaling IPT included limited power to set agendas and control over funding, inadequate resources, lack of motivation of frontline providers, and lack of political prioritization. We found that the SEARCH-IPT intervention supported managers to design and implement strategies to improve IPT uptake and collaborate between districts. This may have contributed to the overall intervention effect in increasing the uptake of IPT among PLHIV compared to standard practice.

Trial registration
ClinicalTrials.gov, NCT03315962, Registered 20 October 2017.
Body conformation traits in early-lactation associated with clinical mastitis and lameness in lactating Chinese holstein cows
Authors: Zhang Zhipeng , Yang Jiayu , Yao Yiyang , Wang Dasheng , Lu Xubin , Yang Zhangping 
Published: March 2024

Abstract
Background
Comprehending the correlation between body conformation traits of cows at the early stages of lactation and prevalent lactation diseases might facilitate the execution of selection and feeding strategies that prioritize cow health. This study aimed to evaluate the impact of body conformation traits on the incidence of clinical mastitis and lameness in Chinese Holstein cows. From a pasture herd of 1472 early lactating Chinese Holstein cows, we evaluated 20 body conformation traits. During lactation, this pasture herd was visited weekly to gather clinical mastitis and lameness data. A nine-point scale was used to determine the conformation traits of cows to clarify their linear characters, including frame capacity, rump (RU), feet and leg (FL), mammary system (MS), and dairy character. A longitudinal binary disease (0 = healthy; 1 = diseased) data structure was created by allocating disease records to adjacent official test dates. The impact of body conformation traits on the risk of developing diseases (clinical mastitis and lameness) was analyzed using the logistic regression models.

Results
Compared to cows with low total scores (75–79 points), those with high total scores (80–85 points) of body conformation traits had a significantly lower risk of mastitis (P < 0.001). The disease status (0 or 1: binary variable) of clinical mastitis in lactating cows was significantly impacted negatively by age (P < 0.05). The fore udder attachment (FUA), angularity, rear attachment height (RAH), and rear teat placement (RTP) were all significantly associated with clinical mastitis during lactation (P < 0.05). The rear leg-rear view (RLRV) was significantly correlated with correlated considerably (P < 0.05) with lameness during lactation. An ideal score of four points on the lameness risk dimension of the RLRV may indicate a low risk of lameness. Since the risk of mastitis decreased as this trait score increased, the RTP may be an ideal marker for mastitis risk.

Conclusions
According to the study, clinical mastitis and lameness risks in cows can be estimated using their body conformation traits. Cows with more centrally located rear teats have a lower risk of mastitis. These results may help dairy farmers identify cows at high risk of disease early in lactation and aid in breeding for disease resistance in cows.
Comparison of the gene expression profile of testicular tissue before and after sexual maturity in Qianbei Ma goats
Authors: Chen Jiajing , Chen Xiang , Guo Wei , Tang Wen , Zhang Yuan , Tian Xingzhou , Zou Yue 
Published: March 2024

Abstract
Background
With long-term research on the reproductive ability of Qianbei Ma goat, we found that the puberty of the male goats comes at the age of 3 months and reaches sexual maturity at 4 months,the male goats are identified as physically mature at 9 months and able to mate. Compared with other kinds of breeds of goats, Qianbei Ma goat is featured with more faster growth and earlier sexual maturity.Therefore, in order to explore the laws of growth of Qianbei Ma goat before sexual maturity(3-month-old)and after sexual maturity (9-month-old). The testicular tissue was collected to explore their changes in morphology through HE staining, the serum was collected to detect the hormone content, and the mRNA expression profile of the testis was analyzed by transcriptomics. In this way, the effect of testicular development on the reproduction of Qianbei ma goats was further analyzed.

Results
The results showed that the area and diameter of spermatogenic tubules were larger at 9 months than 3 months, and the number of spermatocytes, interstitial cells, spermatogonia and secondary spermatocytes in the lumen of the tubules showed a similar trend. The appearance of spermatozoa at age 3 months indicated that puberty had begun in Qianbei Ma goats. The Elasa test for testosterone, luteinizing hormone, follicle stimulating hormone and anti-Müllerian hormone showed that the levels of these hormones in the serum at age 9 months were all highly significantly different than those at age 3 months (P < 0.01). There were 490 differentially expressed genes (DEGs) between the (|log2(fold change)| > 1 and p value < 0.05) 3-month-old and 9-month-old groups, of which 233 genes were upregulated and 257 genes were downregulated (3 months of age was used as the control group and 9 months of age was used as the experimental group). According to the GO and KEGG enrichment analyses of DEGs, PRSS58, ECM1, WFDC8 and LHCGR are involved in testicular development and androgen secretion, which contribute to the sexual maturation of Qianbei Ma goats.

Conclusions
Potential biomarker genes and relevant pathways involved in the regulation of testicular development and spermatogenesis in Qianbei Ma goats were identified, providing a theoretical basis and data support for later studies on the influence of testicular development and spermatogenesis before and after sexual maturity in Qianbei Ma goats.
Anatomical studies on the PES region of Zebu cattle (Bos Taurus indicus) with special references to 3D computed tomography imaging technique
Authors: Nomir Ahmed , Sharaby Ashraf El , Abumandour Mohamed M. A. 
Published: March 2024

AbstractThe 3D render volume reconstruction CT (3D-RVCT) produced detailed images of the PES region, determining its relationships with the surrounding structures. Despite extensive research in veterinary studies on the PES through gross anatomy and CT, there is a lack of studies on the PES of zebu cattle. The study aimed to analyze the PES of Zebu cattle using gross cross-sectional, radiographic, CT, and morphometric methods, with the use of 3D-RVCT to provide anatomical guidance for surgeons and students. The study was performed on sixteen PES regions to provide hard and soft tissues in CT images. Three are five tarsal bones and two large fused (III and IV) metatarsal bones that were completely fused except for their distal extremities, which were divided distally by the intertrochlear notch. The cortical thickness of the metatarsal bone was equal on both sides. The bony septum divided the medullary cavity between the two fused large metatarsal bones in the proximal distal half only and disappeared in the middle part. The reconstruction showed similar sizes in the right and left limbs, confirming the pes bones. The radiographic and CT images could be used as a normal reference for the interpretation of some clinical diseases in the PES. The 3D CT reconstruction of the pes bones was described by various CT oblique dorsal and plantar views. The study focuses on diagnosing PES disorders using CT imaging, improving medical interventions, improving Zebu cattle health outcomes, and empowering students to contribute to veterinary medicine research and advancements.
Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8–9 years in a multi-site longitudinal study
Authors: Sherris Allison R. , Loftus Christine T. , Szpiro Adam A. , Dearborn Logan C. , Hazlehurst Marnie F. , Carroll Kecia N. , Moore Paul E. , Adgent Margaret A. , Barrett Emily S. , Bush Nicole R. , Day Drew B. , Kannan Kurunthachalam , LeWinn Kaja Z. , Nguyen Ruby H. N. , Ni Yu , Riederer Anne M. , Robinson Morgan , Sathyanarayana Sheela , Zhao Qi , Karr Catherine J. 
Published: March 2024

Abstract
Background and aim
Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium.

Methods
We included 1,081 birth parent–child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8–9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression.

Results
The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant.

Conclusions
In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8–9 years, though some adverse associations were observed among girls.
circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis
Authors: Zhao Yan , Jia Yunlong , Wang Jiali , Chen Xiaolin , Han Jingya , Zhen Shuman , Yin Shuxian , Lv Wei , Yu Fan , Wang Jiaqi , Xu Fan , Zhao Xinming , Liu Lihua 
Published: March 2024

Abstract
Background
Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain elusive.

Methods
The clinical implications of fibroblast activation protein (FAP)-positive CAFs (FAP+CAFs) were evaluated based on tumor specimens from NSCLC patients and bioinformatic analysis of online databases. CAF-specific circular RNAs (circRNAs) were screened by circRNA microarrays of primary human CAFs and matched normal fibroblasts (NFs). Survival analyses were performed to assess the prognostic value of circNOX4 in NSCLC clinical samples. The biological effects of circNOX4 were investigated by gain- and loss-of-function experiments in vitro and in vivo. Fluorescence in situ hybridization, luciferase reporter assays, RNA immunoprecipitation, and miRNA rescue experiments were conducted to elucidate the underlying mechanisms of fibroblast activation. Cytokine antibody array, transwell coculture system, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the downstream effectors that promote cancer metastasis.

Results
FAP+CAFs were significantly enriched in metastatic cancer samples, and their higher abundance was correlated with the worse overall survival in NSCLC patients. A novel CAF-specific circRNA, circNOX4 (hsa_circ_0023988), evoked the phenotypic transition from NFs into CAFs and promoted the migration and invasion of NSCLC in vitro and in vivo. Clinically, circNOX4 correlated with the poor prognosis of advanced NSCLC patients. Mechanistically, circNOX4 upregulated FAP by sponging miR-329-5p, which led to fibroblast activation. Furthermore, the circNOX4/miR-329-5p/FAP axis activated an inflammatory fibroblast niche by preferentially inducing interleukin-6 (IL-6) and eventually promoting NSCLC progression. Disruption of the intercellular circNOX4/IL-6 axis significantly suppressed tumor growth and metastatic colonization in vivo.

Conclusions
Our study reveals a role of the circRNA-induced fibroblast niche in tumor metastasis and highlights that targeting the circNOX4/FAP/IL-6 axis is a promising strategy for the intervention of NSCLC metastasis.
Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression
Authors: Deng Cuncan , Huo Mingyu , Chu Hongwu , Zhuang Xiaomei , Deng Guofei , Li Wenchao , Wei Hongfa , Zeng Leli , He Yulong , Liu Huashan , Li Jia , Zhang Changhua , Chen Hengxing 
Published: March 2024

AbstractCircular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is highly expressed in both gastric cancer tissues and exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage and worse prognosis in patients with gastric cancer. We showed that the circATP8A1 knockdown significantly inhibited gastric cancer proliferation and invasion in vitro and in vivo. Functionally, exosome circATP8A1 induced the M2 polarization of macrophages through the STAT6 pathway instead of the STAT3 pathway. Mechanistically, circATP8A1 was shown to activate the STAT6 pathway through competitive binding to miR-1-3p, as confirmed by Fluorescence In Situ Hybridization (FISH), RNA immunoprecipitation, RNA pulldown, and Luciferase reporter assays. The reversal of circATP8A1-induced STAT6 pathway activation and macrophage polarization was observed upon blocking miR-1-3p. Macrophages treated with exosomes from gastric cancer cells overexpressing circATP8A1 were able to promote gastric cancer migration, while knockdown of circATP8A1 reversed these effects in vivo. In summary, exosome-derived circATP8A1 from gastric cancer cells induce macrophages M2 polarization via the circATP8A1/miR-1-3p/STAT6 axis, and tumor progression. Our results highlight circATP8A1 as a potential prognostic biomarker and therapeutic target in gastric cancer.
Relative importance of triglyceride glucose index combined with body mass index in predicting recovery from prediabetic state to normal fasting glucose: a cohort analysis based on a Chinese physical examination population
Authors: Yang Hongyi , Kuang Maobin , Qiu Jiajun , He Shiming , Yu Changhui , Sheng Guotai , Zou Yang 
Published: March 2024

Abstract
Background
Prediabetes is a high-risk state for diabetes, and numerous studies have shown that the body mass index (BMI) and triglyceride-glucose (TyG) index play significant roles in risk prediction for blood glucose metabolism. This study aims to evaluate the relative importance of BMI combination with TyG index (TyG-BMI) in predicting the recovery from prediabetic status to normal blood glucose levels.

Methods
A total of 25,397 prediabetic subjects recruited from 32 regions across China. Normal fasting glucose (NFG), prediabetes, and diabetes were defined referring to the American Diabetes Association (ADA) criteria. After normalizing the independent variables, the impact of TyG-BMI on the recovery or progression of prediabetes was analyzed through the Cox regression models. Receiver Operating Characteristic (ROC) curve analysis was utilized to visualize and compare the predictive value of TyG-BMI and its constituent components in prediabetes recovery/progression.

Results
During the average observation period of 2.96 years, 10,305 individuals (40.58%) remained in the prediabetic state, 11,278 individuals (44.41%) recovered to NFG, and 3,814 individuals (15.02%) progressed to diabetes. The results of multivariate Cox regression analysis demonstrated that TyG-BMI was negatively associated with recovery from prediabetes to NFG and positively associated with progression from prediabetes to diabetes. Further ROC analysis revealed that TyG-BMI had higher impact and predictive value in predicting prediabetes recovering to NFG or progressing to diabetes in comparison to the TyG index and BMI. Specifically, the TyG-BMI threshold for predicting prediabetes recovery was 214.68, while the threshold for predicting prediabetes progression was 220.27. Additionally, there were significant differences in the relationship of TyG-BMI with prediabetes recovering to NFG or progressing to diabetes within age subgroups. In summary, TyG-BMI is more suitable for assessing prediabetes recovery or progression in younger populations (< 45 years old).

Conclusions
This study, for the first time, has revealed the significant impact and predictive value of the TyG index in combination with BMI on the recovery from prediabetic status to normal blood glucose levels. From the perspective of prediabetes intervention, maintaining TyG-BMI within the threshold of 214.68 holds crucial significance.
CD146+CAFs promote progression of endometrial cancer by inducing angiogenesis and vasculogenic mimicry via IL-10/JAK1/STAT3 pathway
Authors: Yu Zhicheng , Zhang Qian , Wei Sitian , Zhang Yang , Zhou Ting , Zhang Qi , Shi Rui , Zinovkin Dmitry , Pranjol Zahidul Islam , Zhang Jun , Wang Hongbo 
Published: March 2024

AbstractHeterogeneous cancer-associated fibroblasts (CAFs) play important roles in cancer progression. However, the specific biological functions and regulatory mechanisms involved in endometrial cancer have yet to be elucidated. We aimed to explore the potential mechanisms of heterogeneous CAFs in promoting endometrial cancer progression. The presence of melanoma cell adhesion molecule (MCAM; CD146) positive CAFs was confirmed by tissue multi-immunofluorescence (mIF), and fluorescence activated cell sorting (FACS). The biological functions were determined by wound healing assays, tuber formation assays and cord formation assays. The effects of CD146+CAFs on endometrial cancer cells were studied in vitro and in vivo. The expression level of interleukin 10 (IL-10) was measured by quantitative real time polymerase chain reaction (qRT-PCR), western boltting and enzyme linked immunosorbent assays (ELISAs). In addition, the transcription factor STAT3 was identified by bioinformatics methods and chromatin immunoprecipitation (ChIP). A subtype of CAFs marked with CD146 was found in endometrial cancer and correlated with poor prognosis. CD146+CAFs promoted angiogenesis and vasculogenic mimicry (VM) in vitro. A xenograft tumour model also showed that CD146+CAFs can facilitate tumour progression. The expression of IL-10 was elevated in CD146+CAFs. IL-10 promoted epithelial-endothelial transformation (EET) and further VM formation in endometrial cancer cells via the janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signalling pathway. This process could be blocked by the JAK1/STAT3 inhibitor niclosamide. Mechanically, STAT3 can bind to the promoter of cadherin5 (CDH5) to promote its transcription which may be stimulated by IL-10. We concluded that CD146+CAFs could promote angiogenesis and VM formation via the IL-10/JAK1/STAT3 signalling pathway. These findings may lead to the identification of potential targets for antiangiogenic therapeutic strategies for endometrial cancers.