bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between HIV Serostatus and premalignant cervical lesions among women attending a cervical cancer screening clinic at a tertiary care facility in southwestern Uganda: a comparative cross-sectional study
Authors: Kirabira Justus , Kayondo Musa , Bawakanya Stephen Mayanja , Nsubuga Edirisa Juniour , Yarine Fajardo , Namuli Alexcer , Namugumya Rita , Natulinda Christine Hilda , Atwine Raymond , Birungi Abraham , Lugobe Henry Mark , Tibaijuka Leevan , Kisombo Dean , Jjuuko Mark , Agaba David Collins , Saturday Pascal , Atupele Subira Mlangwa , Tumusiime Matthew , Migisha Richard , Kajabwangu Rogers 
Published: April 2024

Abstract
Background
Uganda has approximately 1.2 million people aged 15–64 years living with human immunodeficiency virus (HIV). Previous studies have shown a higher prevalence of premalignant cervical lesions among HIV-positive women than among HIV-negative women. Additionally, HIV-infected women are more likely to have human papilloma virus (HPV) infection progress to cancer than women not infected with HIV. We determined the prevalence of premalignant cervical lesions and their association with HIV infection among women attending a cervical cancer screening clinic at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda.

Methods
We conducted a comparative cross-sectional study of 210 women aged 22–65 years living with HIV and 210 women not living with HIV who were systematically enrolled from March 2022 to May 2022. Participants were subjected to a structured interviewer-administered questionnaire to obtain their demographic and clinical data. Additionally, Papanicolaou smears were obtained for microscopy to observe premalignant cervical lesions. Multivariate logistic regression was performed to determine the association between HIV status and premalignant cervical lesions.

Results
The overall prevalence of premalignant cervical lesions in the study population was 17% (n = 72; 95% C.I: 14.1–21.4), with 23% (n = 47; 95% C.I: 17.8–29.5) in women living with HIV and 12% (n = 25; 95% C.I: 8.2–17.1) in women not living with HIV (p < 0.003). The most common premalignant cervical lesions identified were low-grade squamous intraepithelial lesions (LSIL) in both women living with HIV (74.5%; n = 35) and women not living with HIV (80%; n = 20). HIV infection was significantly associated with premalignant lesions (aOR: 2.37, 95% CI: 1.27–4.42; p = 0.007).

Conclusion
Premalignant cervical lesions, particularly LSILs, were more common in HIV-positive women than in HIV-negative women, highlighting the need to strengthen the integration of cervical cancer prevention strategies into HIV care programs.
An improved system to generate recombinant canine distemper virus
Authors: Cheng Huai , Zhang Hewei , Zhang Huayun , Cai Huanchang , Liu Min , Yu Mingen , Xiang Meihua , Wen Shubo , Ren Jingqiang 
Published: April 2024

Abstract
Background
Canine distemper virus (CDV) is a pathogen with the capability of cross-species transmission. It has crossed the species barrier to infect many other species, and its host range is expanding. The reverse genetic platform, a useful tool for scientific research, allows the generation of recombinant viruses from genomic cDNA clones in vitro.

Methods
To improve the reverse genetic system of CDV, a plasmid containing three independent expression cassettes was constructed for co-expression of the N, P, and L genes and then transfected with a full-length cDNA clone of CDV into Vero cells.

Results
The results indicated that the established rescue system has the advantages of being more convenient, easy to control the transfection ratio, and high rescue efficiency compared with the conventional reverse genetics system.

Conclusion
This method not only reduces the number of transfection plasmids, but also improves the rescue efficiency of CDV, which could provide a reference for the recovery of other morbilliviruses.
Predicting lung function decline in cystic fibrosis: the impact of initiating ivacaftor therapy
Authors: Zhou Grace C. , Wang Ziyun , Palipana Anushka K. , Andrinopoulou Eleni-Rosalina , Miranda Afonso Pedro , McPhail Gary L. , Siracusa Christopher M. , Gecili Emrah , Szczesniak Rhonda D. 
Published: April 2024

Abstract
Background
Modulator therapies that seek to correct the underlying defect in cystic fibrosis (CF) have revolutionized the clinical landscape. Given the heterogeneous nature of lung disease progression in the post-modulator era, there is a need to develop prediction models that are robust to modulator uptake.

Methods
We conducted a retrospective longitudinal cohort study of the CF Foundation Patient Registry (N = 867 patients carrying the G551D mutation who were treated with ivacaftor from 2003 to 2018). The primary outcome was lung function (percent predicted forced expiratory volume in 1 s or FEV1pp). To characterize the association between ivacaftor initiation and lung function, we developed a dynamic prediction model through covariate selection of demographic and clinical characteristics. The ability of the selected model to predict a decline in lung function, clinically known as an FEV1-indicated exacerbation signal (FIES), was evaluated both at the population level and individual level.

Results
Based on the final model, the estimated improvement in FEV1pp after ivacaftor initiation was 4.89% predicted (95% confidence interval [CI]: 3.90 to 5.89). The rate of decline was reduced with ivacaftor initiation by 0.14% predicted/year (95% CI: 0.01 to 0.27). More frequent outpatient visits prior to study entry and being male corresponded to a higher overall FEV1pp. Pancreatic insufficiency, older age at study entry, a history of more frequent pulmonary exacerbations, lung infections, CF-related diabetes, and use of Medicaid insurance corresponded to lower FEV1pp. The model had excellent predictive accuracy for FIES events with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.83 to 0.84) for the independent testing cohort and 0.90 (95% CI: 0.89 to 0.90) for 6-month forecasting with the masked cohort. The root-mean-square errors of the FEV1pp predictions for these cohorts were 7.31% and 6.78% predicted, respectively, with standard deviations of 0.29 and 0.20. The predictive accuracy was robust across different covariate specifications.

Conclusions
The methods and applications of dynamic prediction models developed using data prior to modulator uptake have the potential to inform post-modulator projections of lung function and enhance clinical surveillance in the new era of CF care.
Carbon dioxide valorization into resveratrol via lithoautotrophic fermentation using engineered Cupriavidus necator H16
Authors: Jang Yongjae , Lee Yeon Ji , Gong Gyeongtaek , Lee Sun-Mi , Um Youngsoon , Kim Kyoung Heon , Ko Ja Kyong 
Published: April 2024

Abstract
Background
Industrial biomanufacturing of value-added products using CO2 as a carbon source is considered more sustainable, cost-effective and resource-efficient than using common carbohydrate feedstocks. Cupriavidus necator H16 is a representative H2-oxidizing lithoautotrophic bacterium that can be utilized to valorize CO2 into valuable chemicals and has recently gained much attention as a promising platform host for versatile C1-based biomanufacturing. Since this microbial platform is genetically tractable and has a high-flux carbon storage pathway, it has been engineered to produce a variety of valuable compounds from renewable carbon sources. In this study, the bacterium was engineered to produce resveratrol autotrophically using an artificial phenylpropanoid pathway.

Results
The heterologous genes involved in the resveratrol biosynthetic pathway—tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), and stilbene synthase (STS) —were implemented in C. necator H16. The overexpression of acetyl-CoA carboxylase (ACC), disruption of the PHB synthetic pathway, and an increase in the copy number of STS genes enhanced resveratrol production. In particular, the increased copies of VvSTS derived from Vitis vinifera resulted a 2-fold improvement in resveratrol synthesis from fructose. The final engineered CR-5 strain produced 1.9 mg/L of resveratrol from CO2 and tyrosine via lithoautotrophic fermentation.

Conclusions
To the best of our knowledge, this study is the first to describe the valorization of CO2 into polyphenolic compounds by engineering a phenylpropanoid pathway using the lithoautotrophic bacterium C. necator H16, demonstrating the potential of this strain a platform for sustainable chemical production.
circ-TFRC downregulation suppresses ovarian cancer progression via miR-615-3p/IGF2 axis regulation
Authors: Yan Zhongxin , Duan Changling , Li Xi , Wang Hao , Li Shanji , Zhou Xuexin , Miao Yi 
Published: April 2024

Abstract
Background
Ovarian cancer (OC) is a malignancy among female globally. Circular RNAs (circRNAs) are a family of circular endogenous RNAs generated from selective splicing, which take part in many traits. Former investigation suggested that circ-TFRC was abnormally expressed in breast cancer (BC). Further, the role of circ-TFRC to the progress of OC remains unclear. So, the aim of this study was to reveal the regulatory mechanism of circ-TFRC.

Methods
Our team made the luciferase reporter assay to validate circ-TFRC downstream target. Transwell migration assay, 5-ethynyl-20-deoxyuridine, and cell counting kit-8 were applied to investigate both proliferation and migration. In vivo tumorigenesis and metastasis assays were performed to investigate the circ-TFRC role in OC.

Results
The outputs elucidated that circ-TFRC expression incremented in OC cells and tissues. circ-TFRC downregulation inhibited OC cell proliferation as well as migration in in vivo and in vitro experiments. The luciferase results validated that miR-615-3p and IGF2 were circ-TFRC downstream targets. IGF2 overexpression or miR-615-3p inhibition reversed OC cell migration after circ-TFRC silencing. Also, IGF2 overexpression reversed OC cell migration and proliferation post miR-615-3p upregulation.

Conclusion
Results demonstrate that circ-TFRC downregulation inhibits OC progression and metastasis via IGF2 expression regulation and miR-615-3psponging.
Fidelity of implementation of national guidelines on malaria diagnosis for children under-five years in Rivers State, Nigeria
Authors: Whyte Mina , Ibisomi Latifat , Chirwa Tobias , Levin Jonathan , Slemming Wiedaad 
Published: April 2024

Abstract
Background
Malaria is still a disease of global public health importance and children under-five years of age are the most vulnerable to the disease. Nigeria adopted the “test and treat” strategy in the national malaria guidelines as one of the ways to control malaria transmission. The level of adherence to the guidelines is an important indicator for the success or failure of the country’s roadmap to malaria elimination by 2030. This study aimed to assess the fidelity of implementation of the national guidelines on malaria diagnosis for children under-five years and examine its associated moderating factors in health care facilities in Rivers State, Nigeria.

Methods
This was a descriptive, cross-sectional study conducted in Port Harcourt metropolis. Data were collected from 147 public, formal private and informal private health care facilities. The study used a questionnaire developed based on Carroll’s Conceptual Framework for Implementation Fidelity. Frequency, mean and median scores for implementation fidelity and its associated factors were calculated. Associations between fidelity and the measured predictors were examined using Mann Whitney U test, Kruskal Wallis test, and multiple linear regression modelling using robust estimation of errors. Regression results are presented in adjusted coefficient (β) and 95% confidence intervals.

Results
The median (IQR) score fidelity score for all participants was 65% (43.3, 85). Informal private facilities (proprietary patent medicine vendors) had the lowest fidelity scores (47%) compared to formal private (69%) and public health facilities (79%). Intervention complexity had a statistically significant inverse relationship to implementation fidelity (β = − 1.89 [− 3.42, − 0.34]). Increase in participant responsiveness (β = 8.57 [4.83, 12.32]) and the type of malaria test offered at the facility (e.g., RDT vs. no test, β = 16.90 [6.78, 27.03]; microscopy vs. no test, β = 21.88 [13.60, 30.16]) were positively associated with fidelity score.

Conclusions
This study showed that core elements of the “test and treat” strategy, such as testing all suspected cases with approved diagnostic methods before treatment, are still not fully implemented by health facilities. There is a need for strategies to increase fidelity, especially in the informal private health sector, for malaria elimination programme outcomes to be achieved.
Associations between non-insulin-based insulin resistance indices and heart failure prevalence in overweight/obesity adults without diabetes mellitus: evidence from the NHANES 2001–2018
Authors: Cui Di-yu , Zhang Chao , Chen Yi , Qian Gang-zhen , Zheng Wan-xiang , Zhang Zhi-hui , Zhang Yu , Zhu Ping 
Published: April 2024

Abstract
Background
The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes.

Methods
This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose–response relationships.

Results
A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4–4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1–1.3, p < 0.001) both increased the prevalence of HF, especially in the non-Hispanic population. Dose–response relationships suggested nonlinear relationships between these two indicators and HF.

Conclusion
Our study demonstrated that elevated TyG index and TG/HDL-C ratio were closely associated with the prevalence of HF, and both exhibited nonlinear relationships with HF prevalence in overweight/obesity adults without diabetes. Based on these findings, additional prospective studies are needed for further validation.
Receipt of COVID-19 emergency funds and engagement in sex work during COVID-19 among people who use drugs: evidence from Vancouver, Canada
Authors: McAdam Erica , Hayashi Kanna , Cui Zishan , Anderson Haleigh , Nelson Scarlett , Milloy M.-J. , DeBeck Kora 
Published: April 2024

Abstract
Background
During the early period of the COVID-19 pandemic, public health orders disrupted income generation in numerous sectors and many governments provided emergency financial support. Access to government support and changes in engagement in sex work during the early period of the pandemic among people who use drugs (PWUD) are not well described. In the present study, we investigate the prevalence and correlates of engaging in sex work during the COVID-19 pandemic, among PWUD in Vancouver, Canada.

Methods
Data derived from three harmonized cohorts of PWUD. Using multivariable logistic regression, we characterized factors associated with engaging in sex work in the last month between July 17 and November 30, 2020. Reports of changes in frequency of engagement in sex work since the pandemic were also collected.

Results
Of the 864 individuals included in this analysis, 55 (6.4%) reported sex work engagement in the last month. Among these participants, 40.7% reported receiving COVID-19 income support in the past month vs. 52.7% of the rest of the sample, though receipt of income support in the past six months was similar between the two groups (72.2% vs. 75.7%, p = 0.624). In multivariable analysis, receipt of financial support in the last month was negatively associated with engagement in sex work in the last month (adjusted odds ratio [AOR] = 0.44 [95% confidence interval [CI]: 0.24–0.81]). Among 69 participants who responded to a question regarding changes in engagement in sex work, 38 (55.1%) reported a decrease, 11 (15.9%) reported an increase, 19 (27.5%) reported no change, and 1 (1.4%) reported cessation.

Conclusions
Findings document that engagement in sex work appears to have declined early in the pandemic. Participants who received income support in the past month were less likely to report recent engagement in sex work. Findings suggest that recent receipt of income support may have contributed to reductions in engagement in sex work. Additional investigation is warranted.
Low-grade undifferentiated sarcoma with MEIS1::NCOA2-rearrangement primary to the lung: a case report
Authors: Coty-Fattal Zachary , Carter Bianca , Volek Michael J. , Obeidin Farres 
Published: April 2024

Abstract
Background
MEIS1::NCOA2 is a rare fusion gene that has been recently described in a subset of spindle cell rhabdomyosarcomas and multiple low-grade undifferentiated spindle cell sarcomas predominantly arising in the genitourinary and gynecologic tracts with no specific line of differentiation. We present the first documented case of this neoplasm arising as a lung primary tumor.

Case Presentation
A 74-year-old woman with a 40-year smoking history presented with a 2.1 × 1.7 cm lung nodule discovered on computed tomography (CT) scan. A biopsy and subsequent lobe resection were performed, as well as an extensive metastatic work up, which revealed no additional masses. No specific line of differentiation was found by immunohistochemical staining, and an RNA-based fusion panel revealed a MEIS1::NCOA2 fusion, at which point a diagnosis of Low-Grade Undifferentiated Sarcoma with MEIS1::NCOA2-Rearrangement was rendered.

Conclusions
This report represents the first diagnosis of this tumor primary to the lung, and provides additional insight into the origin and localization of these rare tumors.
The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway
Authors: Abdi Arash , Ranjbaran Mina , Amidi Fardin , Akhondzadeh Fariba , Seifi Behjat 
Published: April 2024

Abstract
Objective
The present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochondrial dynamic via PI3K-AKT pathway.

Methods
Thirty-two female rats were randomly divided into four experimental groups: Sham, PCOS, PCOS + MSCs, and PCOS + MSCs + LY294002. The Sham group received 0.5% w/v carboxymethyl cellulose (CMC); the PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. Animals in the PCOS + MSCs group received 1 × 106 MSCs/rat (i.p,) on the 22th day of the study. In the PCOS + MSCs + LY294002 group, rats received LY294002 (PI3K-AKT inhibitor) 40 min before MSC transplantation. Mitochondrial dynamic gene expression, mitochondrial membrane potential (MMP), citrate synthase (CS) activity, oxidative stress, inflammation, ovarian histological parameters, serum hormone levels, homeostatic model assessment for insulin resistance (HOMA-IR), insulin and glucose concentrations, p-PI3K and p-AKT protein levels were evaluated at the end of the experiment.

Results
PCOS rats showed a significant disruption of mitochondrial dynamics and histological changes, lower MMP, CS, ovary super oxide dismutase (SOD) and estrogen level. They also had a notable rise in insulin and glucose concentrations, HOMA-IR, testosterone level, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, ovarian malondialdehyde (MDA) content as well as a notable decrease in p-PI3K and p-AKT protein levels compared to the Sham group. In the PCOS + MSCs group, the transplantation of MSCs could improve the above parameters. Administration of LY294002 (PI3K-AKT pathway inhibitor) deteriorated mitochondrial dynamic markers, oxidative stress status, inflammation markers, hormonal levels, glucose, and insulin levels and follicular development compared to the PCOS + MSCs group.

Conclusions
This study demonstrated that the protective effects of MSC transplantation in regulating mitochondrial dynamics, promoting mitochondrial biogenesis, competing with redox status and inflammation response were mainly mediated through the PI3K-AKT pathway in the PCOS model.
Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress
Authors: Taylor Bethany C. , Steinthal Loic H. , Dias Michelle , Yalamanchili Hari Krishna , Ochsner Scott A. , Zapata Gladys E. , Mehta Nitesh R. , McKenna Neil J. , Young Nicolas L. , Nuotio-Antar Alli M. 
Published: April 2024

Abstract
Background
Regulation of the thermogenic response by brown adipose tissue (BAT) is an important component of energy homeostasis with implications for the treatment of obesity and diabetes. Our preliminary analyses of RNA-Seq data uncovered many nodes representing epigenetic modifiers that are altered in BAT in response to chronic thermogenic activation. Thus, we hypothesized that chronic thermogenic activation broadly alters epigenetic modifications of DNA and histones in BAT.

Results
Motivated to understand how BAT function is regulated epigenetically, we developed a novel method for the first-ever unbiased top-down proteomic quantitation of histone modifications in BAT and validated our results with a multi-omic approach. To test our hypothesis, wildtype male C57BL/6J mice were housed under chronic conditions of thermoneutral temperature (TN, 28°C), mild cold/room temperature (RT, 22°C), or severe cold (SC, 8°C) and BAT was analyzed for DNA methylation and histone modifications. Methylation of promoters and intragenic regions in genomic DNA decrease in response to chronic cold exposure. Integration of DNA methylation and RNA expression datasets suggest a role for epigenetic modification of DNA in regulation of gene expression in response to cold. In response to cold housing, we observe increased bulk acetylation of histones H3.2 and H4, increased histone H3.2 proteoforms with di- and trimethylation of lysine 9 (K9me2 and K9me3), and increased histone H4 proteoforms with acetylation of lysine 16 (K16ac) in BAT.

Conclusions
Our results reveal global epigenetically-regulated transcriptional “on” and “off” signals in murine BAT in response to varying degrees of chronic cold stimuli and establish a novel methodology to quantitatively study histones in BAT, allowing for direct comparisons to decipher mechanistic changes during the thermogenic response. Additionally, we make histone PTM and proteoform quantitation, RNA splicing, RRBS, and transcriptional footprint datasets available as a resource for future research.