bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attitudes and experiences with fentanyl contamination of methamphetamine: exploring self-reports and urine toxicology among persons who use methamphetamine and other drugs
Authors: Daniulaityte Raminta , Ruhter Lance , Juhascik Matthew , Silverstein Sydney 
Published: April 2023

Abstract
Background
There are growing concerns about illicitly manufactured fentanyl (IMF) contamination of methamphetamine. This study aims to characterize the lay views and experiences with IMF-contaminated methamphetamine (IMF/meth) and identify participants with unknown IMF exposures through urine toxicology analysis.

Methods
Between December-2019 and November-2021, structured interviews were conducted with 91 individuals who reported past 30-day use of methamphetamine and resided in Dayton, Ohio, USA. Lab-based urine toxicology analyses were conducted to identify fentanyl/analogs, methamphetamine, and other drugs. Bivariate analyses were conducted to identify characteristics associated with attitudes and experiences with IMF/meth, and unknown IMF exposures.

Results
The majority (95.6%) of the study participants were non-Hispanic white, and 52.7% were female. Past 30-day use of methamphetamine was reported on a mean of 18.7 (SD 9.1) days, and 62.6% also reported past 30-day use of heroin/IMF. Most (76.9%) had a history of an unintentional drug-related overdose, but 38.5% rated their current risk for an opioid overdose as none. Besides fentanyl (71.9%), toxicology analysis identified nine fentanyl analogs/metabolites (e.g., 42.7% acetyl fentanyl, 19.0% fluorofentanyl, 5.6% carfentanil), and 12.4% tested positive for Xylazine. The majority (71.4%) believed that IMF/meth was common, and 59.3% reported prior exposures to IMF/meth. 11.2% tested positive for IMF but reported no past 30-day heroin/IMF use (unknown exposure to IMF). Views that IMF/meth was common showed association with homelessness (p = 0.04), prior overdose (p = 0.028), and greater perceived risk of opioid overdose (p = 0.019). Self-reported exposure to IMF/meth was associated with homelessness (p = 0.007) and obtaining take-home naloxone (p = 0.025). Individuals with unknown IMF exposure (test positive for IMF, no reported past 30-day heroin/IMF use) were older (49.9 vs. 41.1 years, p < 0.01), and reported more frequent past 30-day use of methamphetamine (24.4 vs. 18.0 days, p < 0.05). They indicated lower perceived risk of opioid overdose (0.1 vs. 1.9, scale from 0 = “none” to 4 = “high,” p < 0.001).

Discussion
This study suggests a need for targeted interventions for people who use methamphetamine and expansion of drug checking and other harm reduction services.
The emerging role of lysine succinylation in ovarian aging
Authors: Le Meiling , Li Jia , Zhang Dalei , Yuan Yuan , Zhou Chong , He Jinxia , Huang Jian , Hu Liaoliao , Luo Tao , Zheng Liping 
Published: April 2023

Abstract
Background
Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc.

Methods
The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level.

Results
Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc.

Conclusion
The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.
Brassicasterol inhibits hepatitis B virus-associated hepatocellular carcinoma development via suppression of AKT signaling pathway
Authors: Zeng Jindi , Wu Jiancheng , Pang Shuijiao , Wang Feifei , Yu Xin , Zhang Shouhua , Zeng Junquan , Yan Jinlong , Lian Jianping 
Published: April 2023

Abstract
Background
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for developing therapeutical strategies for HBV + HCC. Brassicasterol has previously shown anti-cancer and anti-viral activities, however, its value against HBV + HCC remains to be explored.

Methods
The inhibitory effect of brassicasterol and sorafenib was evaluated on HBV + HCC cell lines and xenograft mouse model. The cytotoxicity of brassicasterol on normal liver cells were measured by LDH assay. AKT agonist was used to identify the targeted signaling pathway by brassicasterol.

Results
Brassicasterol induced HBV + HCC cell death in a both dose-dependent and time-dependent manner, and such inhibition was more potent than sorafenib. Brassicasterol did not show apparent cytotoxicity to normal liver cells. Xenograft mouse model further confirmed the inhibitory effect of brassicasterol on the growth of HBV + HCC. Furthermore, signaling pathway analysis showed that brassicasterol-treated HBV + HCC cells had decreased level of phosphor-AKT expression while the addition of AKT agonist could counteract the inhibitory effect of brassicasterol on HCC, indicating that brassicasterol suppressed AKT pathway to exhibit anti-cancer activity in HBV + HCC cells. In addition, brassicasterol showed similar levels of inhibition on HBV− and HBV + HCC cells.

Conclusion
Brassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection.
Regulation of ERα-dependent breast cancer metastasis by a miR-29a signaling
Authors: Lü Jinhui , Zhao Qian , Guo Yuefan , Li Danni , Xie Heying , Liu Cuicui , Hu Xin , Liu Suling , Hou Zhaoyuan , wei Xunbin , Zheng Deyou , Pestell Richard G. , Yu Zuoren 
Published: April 2023

AbstractMalignant breast cancer (BC) remains incurable mainly due to the cancer cell metastasis, which is mostly related to the status of Estrogen receptor alpha (ERα). However, our understanding of the mechanisms through which ERα regulates cancer cell metastasis remains limited. Here we identified a miR-29a-PTEN-AKT axis as a downstream signaling pathway of ERα governing breast cancer progression and metastasis. Two estrogen response element (ERE) half sites were identified in the promoter and enhancer regions of miR-29a, which mediated transcriptional regulation of miR-29a by ERα. Low level of miR-29a showed association with reduced metastasis and better survival in ERα+ luminal subtype of BC. In contrast, high level of miR-29a was detected in ERα- triple negative breast cancer (TNBC) in association with distant metastasis and poor survival. miR-29a overexpression in BC tumors increased the number of circulating tumor cells and promoted lung metastasis in mice. Targeted knockdown of miR-29a in TNBC cells in vitro or administration of a nanotechnology-based anti-miR-29a delivery in TNBC tumor-bearing mice in vivo suppressed cellular invasion, EMT and lung metastasis. PTEN was identified as a direct target of miR-29a, inducing EMT and metastasis via AKT signaling. A small molecular inhibitor of AKT attenuated miR-29a-induced EMT. These findings demonstrate a novel mechanism responsible for ERα-regulated breast cancer metastasis, and reveal the combination of ERα status and miR-29a levels as a new risk indicator in BC.
Racial differences in RAD51 expression are regulated by miRNA-214-5P and its inhibition synergizes with olaparib in triple-negative breast cancer
Authors: Mani Chinnadurai , Acharya Ganesh , Saamarthy Karunakar , Ochola Damieanus , Mereddy Srinidhi , Pruitt Kevin , Manne Upender , Palle Komaraiah 
Published: April 2023

Abstract
Background

Triple-negative breast cancer (TNBC) affects young women and is the most aggressive subtype of breast cancer (BC). TNBCs disproportionally affect women of African-American (AA) descent compared to other ethnicities. We have identified DNA repair gene RAD51 as a poor prognosis marker in TNBC and its posttranscriptional regulation through microRNAs (miRNAs). This study aims to delineate the mechanisms leading to RAD51 upregulation and develop novel therapeutic combinations to effectively treat TNBCs and reduce disparity in clinical outcomes.

Methods
Analysis of TCGA data for BC cohorts using the UALCAN portal and PrognoScan identified the overexpression of RAD51 in TNBCs. miRNA sequencing identified significant downregulation of RAD51-targeting miRNAs miR-214-5P and miR-142-3P. RT-PCR assays were used to validate the levels of miRNAs and RAD51, and immunohistochemical and immunoblotting techniques were used similarly for RAD51 protein levels in TNBC tissues and cell lines. Luciferase assays were performed under the control of RAD51 3’-UTR to confirm that miR-214-5P regulates RAD51 expression. To examine the effect of miR-214-5P-mediated downregulation of RAD51 on homologous recombination (HR) in TNBC cells, Dr-GFP reporter assays were performed. To assess the levels of olaparib-induced DNA damage responses in miR-214-5P, transfected cells, immunoblots, and immunofluorescence assays were used. Furthermore, COMET assays were used to measure DNA lesions and colony assays were performed to assess the sensitivity of BRCA-proficient TNBC cells to olaparib.

Results
In-silico analysis identified upregulation of RAD51 as a poor prognostic marker in TNBCs. miRNA-seq data showed significant downregulation of miR-214-5P and miR-142-3P in TNBC cell lines derived from AA women compared to Caucasian-American (CA) women. miR-214-5P mimics downregulated RAD51 expression and induces HR deficiency as measured by Dr-GFP assays in these cell lines. Based on these results, we designed a combination treatment of miR-214-5P and olaparib in HR-proficient AA TNBC cell lines using clonogenic survival assays. The combination of miR-214-5P and olaparib showed synergistic lethality compared to individual treatments in these cell lines.

Conclusions
Our studies identified a novel epigenetic regulation of RAD51 in TNBCs by miR-214-5P suggesting a novel combination therapies involving miR-214-5P and olaparib to treat HR-proficient TNBCs and to reduce racial disparity in therapeutic outcomes.
ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA
Authors: Huebner Ariana , Black James R. M. , Sarno Francesca , Pazo Roberto , Juez Ignacio , Medina Laura , Garcia-Carbonero Rocio , Guillén Carmen , Feliú Jaime , Alonso Carolina , Arenillas Carlota , Moreno-Cárdenas Ana Belén , Verdaguer Helena , Macarulla Teresa , Hidalgo Manuel , McGranahan Nicholas , Toledo Rodrigo A. 
Published: April 2023

AbstractBackgroundLiquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution.MethodsTo interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity.ResultsSCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour.ConclusionsThis work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.
The role of Iran's context for the development of health technology assessment: challenges and solutions
Authors: Behzadifar Meysam , Behzadifar Masoud , Saran Maryam , Shahabi Saeed , Bakhtiari Ahad , Azari Samad , Bragazzi Nicola Luigi 
Published: April 2023

AbstractHealth technology assessment (HTA) is a comprehensive and structured evaluation that aims to analyze the potential impacts of health technologies, including medical devices, diagnostic tools, pharmaceuticals, and public health interventions. Its purpose is to provide policymakers with evidence-based information to inform decisions related to the utilization and implementation of these technologies. HTA allows for the comparison of various scenarios related to a technology across a wide range of factors. This can aid in the creation of an essential drug list and health benefits package that is tailored to the actual needs of the community within a given healthcare system. In the present paper, we review the role of Iran's context for the development of HTA, in terms of challenges and solutions.
Longitudinal trends and determinants of stunting among children aged 1–15 years
Authors: Wake Senahara Korsa , Zewotir Temesgen , Lulu Kebede , Fissuh Yemane Hailu 
Published: April 2023

AbstractBackgroundStunting increases morbidity and mortality, hindering mental development and influencing cognitive capacity of children. This study aimed to examine the trends and determinants of stunting from infancy to middle adolescence in four countries: Ethiopia, India, Peru, and Vietnam.MethodsA 15-year longitudinal data on the trends of stunting were obtained from the Young Lives cohort study. The study includes 38,361 observations from 4 countries. A generalized mixed-effects model was adopted to estimate the determinant of stunting.ResultsThe patterns of stunting in children from aged 1 to 15 years have declined from an estimated 30% in 2002 to 20% in 2016. Stunting prevalence varied among four low- and middle-income countries with children in Ethiopia, India, and Peru being more stunted compared to children in Vietnam. The highest stunted was recorded in India and the lowest was recorded in Vietnam. In all four countries, the highest prevalence of severe stunting was observed in 2002 and moderate stunting was observed in 2006. Parents’ education level played a significance role in determining a child stunting. Children of uneducated parents were shown to be at a higher risk of stunting.ConclusionDisparities of stunting were observed between- and within-country of four low- and middle-income with the highest prevalence recorded in low-income country. Child stunting is caused by factors related to child’s age, household wealth, household size, the mother’s and father’s education level, residence area and access to save drinking water.
Ecological interactions and the underlying mechanism of anammox and denitrification across the anammox enrichment with eutrophic lake sediments
Authors: Zhang Dandan , Yu Huang , Yang Yuchun , Liu Fei , Li Mingyue , Huang Jie , Yu Yuhe , Wang Cheng , Jiang Feng , He Zhili , Yan Qingyun 
Published: April 2023

Abstract
Background
Increasing attention has recently been devoted to the anaerobic ammonium oxidation (anammox) in eutrophic lakes due to its potential key functions in nitrogen (N) removal for eutrophication control. However, successful enrichment of anammox bacteria from lake sediments is still challenging, partly due to the ecological interactions between anammox and denitrifying bacteria across such enrichment with lake sediments remain unclear.

Results
This study thus designed to fill such knowledge gaps using bioreactors to enrich anammox bacteria with eutrophic lake sediments for more than 365 days. We continuously monitored the influent and effluent water, measured the anammox and denitrification efficiencies, quantified the anammox and denitrifying bacteria, as well as the related N cycling genes. We found that the maximum removal efficiencies of NH4+ and NO2− reached up to 85.92% and 95.34%, respectively. Accordingly, the diversity of anammox and denitrifying bacteria decreased significantly across the enrichment, and the relative dominant anammox (e.g., Candidatus Jettenia) and denitrifying bacteria (e.g., Thauera, Afipia) shifted considerably. The ecological cooperation between anammox and denitrifying bacteria tended to increase the microbial community stability, indicating a potential coupling between anammox and denitrifying bacteria. Moreover, the nirS-type denitrifiers showed stronger coupling with anammox bacteria than that of nirK-type denitrifiers during the enrichment. Functional potentials as depicted by metagenome sequencing confirmed the ecological interactions between anammox and denitrification. Metagenome-assembled genomes-based ecological model indicated that the most dominant denitrifiers could provide various materials such as amino acid, cofactors, and vitamin for anammox bacteria. Cross-feeding in anammox and denitrifying bacteria highlights the importance of microbial interactions for increasing the anammox N removal in eutrophic lakes.

Conclusions
This study greatly expands our understanding of cooperation mechanisms among anammox and denitrifying bacteria during the anammox enrichment with eutrophic lake sediments, which sheds new insights into N removal for controlling lake eutrophication.
Ultrasound aspects and risk factors associated with urogenital schistosomiasis among primary school children in Mali
Authors: Agniwo Privat , Sidibé Bakary , Diakité Assitan , Niaré Safiatou Doumbo , Guindo Hassim , Akplogan Ahristode , Ibikounlé Moudachirou , Boissier Jérôme , Dabo Abdoulaye 
Published: April 2023

AbstractBackgroundUrogenital schistosomiasis is endemic in Mali and is a major cause of serious morbidity in large parts of the world. This disease is responsible for many socio-economic and public health issues. The aim of this study was to investigate the impact of the disease on morbidity and to describe demographic and socioeconomic factors in relation to the status of children with urogenital schistosomiasis in Mali.MethodsWe conducted a cross-sectional study in November 2021 of 971 children aged 6 to 14 years selected at random from six schools in three districts in the Kayes Region of Mali. Demographic and socioeconomic data were collected on survey forms. Clinical data were collected following a medical consultation. Hematuria was systematically searched for through the use of strips. The search forSchistosoma haematobiumeggs in urine was done via the filtration method. The urinary tract was examined by ultrasound. Associations between each of these variables and disease infection were tested using multivariate logistic regression.ResultsThe overall prevalence of urinary schistosomiasis detected was 50.2%. The average intensity of infection was 36 eggs/10 ml of urine. The associated risk factors for urogenital schistosomiasis showed that children who bathed, used the river/pond as a domestic water source, and who habitually urinated in the river/pond were more affected (P < 0.05). Children with farming parents were most affected (P = 0.032). The collection of clinical signs revealed that boys had more pollakiuria (58.6%) and dysuria (46.4%) than girls. Ultrasound data showed that focal lesion rates were recorded in all villages with the lowest rate in Diakalel (56.1%). Ultrasound and parasitological findings showed that irregularity and thickening were strongly associated with urinary schistosomiasis (P < 0.0001).ConclusionsSchistosoma haematobiuminfection was still endemic in the study site despite more than a decade of mass treatment with praziquantel. However, the high percentage of symptoms associated with high intensity reinforces the idea that further studies in terms of schistosomiasis-related morbidity are still needed.
Cost-effectiveness of remdesivir for the treatment of hospitalized patients with COVID-19: a systematic review
Authors: Rezapour Aziz , Behroozi Zahra , Nasirzadeh Mostafa , Rezaeian Mohsen , Barzegar Mohammad , Tashakori-Miyanroudi Mahsa , Sayyad Abdollah , Souresrafil Aghdas 
Published: April 2023

Abstract
Background
Remdesivir is being studied and used to treat coronavirus disease 2019 (COVID-19). This study aimed to systematically identify, critically evaluate, and summarize the findings of the studies on the cost-effectiveness of remdesivir in the treatment of hospitalized patients with COVID-19.

Methods
In this systematic review, PubMed, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched for studies published between 2019 and 2022. We included all full economic evaluations of remdesivir for the treatment of hospitalized patients with COVID-19. Data were summarized in a structured and narrative manner.

Results
Out of 616 articles obtained in this literature search, 12 studies were included in the final analysis. The mean score of the Quality of Health Economic Studies (QHES) for the studies was 87.66 (high quality). All studies were conducted in high-income countries (eight studies in the USA and one study in England), except for three studies from middle-to-high-income countries (China, South Africa, and Turkey). Six studies conducted their economic analysis in terms of a health system perspective; five studies conducted their economic analysis from a payer perspective; three studies from the perspective of a health care provider. The results of five studies showed that remdesivir was cost-effective compared to standard treatment. Furthermore, the therapeutic strategy of combining remdesivir with baricitinib was cost-effective compared to remdesivir alone.

Conclusions
Based on the results of the present study, remdesivir appears to be cost-effective in comparison with the standard of care in China, Turkey, and South Africa. Studies conducted in the United States show conflicting results, and combining remdesivir with baricitinib is cost-effective compared with remdesivir alone. However, the cost-effectiveness of remdesivir in low-income countries remains unknown. Thus, more studies in different countries are required to determine the cost-effectiveness of this drug.