bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of KLRC and Ceacam gene expression by miR-141 supports cell proliferation and metastasis in cervical cancer cells
Authors: Dabous Emad , Alalem Mai , Awad Ahmed M. , Elawdan Khaled A. , Tabl Ahmed M. , Elsaka Shorouk , Said Walid , Guirgis Adel A. , Khalil Hany 
Published: September 2024

Abstract
Introduction
MicroRNAs (miRNAs) are single RNA molecules that act as global regulators of gene expression in mammalian cells and thus constitute attractive targets in treating cancer. Here we aimed to investigate the possible involvement of miRNA-141 (miR-141) in cervical cancer and to identify its potential targets in cervical cancer cell lines.

Methods
The level of miR-141 in HeLa and C-33A cells has been assessed using the quantitative real-time PCR (qRT-PCR). A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HeLa cells. The protein profile of killer-like receptor C1 (KLRC1), KLRC3, carcinoembryonic antigen‐related cell adhesion molecule 3 (CAM3), and CAM6 was investigated in HeLa cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced cytokines from transfected HeLa cells.

Results
The expression of miR-141 significantly increased in HeLa and C-33A cells compared to the normal cervical HCK1T cell line. Transfection of HeLa cells with an inhibitor, antagonist miR-141, showed a potent effect on cancer cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HeLa cells overexpressed miR-141 provided a hundred of downregulated genes, including KLRC1, KLRC3, CAM3, and CAM6. KLRC1 and KLRC3 expression profiles markedly depleted in HeLa cells transfected with miR-141 overexpression accompanied by decreasing interleukin 8 (IL-8), indicating the role of miR-141 in avoiding programmed cells death in HeLa cells. Likewise, CAM3 and CAM6 expression reduced markedly in miR-141 transduced cells accompanied by an increasing level of transforming growth factor beta (TGF-β), indicating the impact of miR-141 in cancer cell migration. The IntaRNA program and miRWalk were used to check the direct interaction and potential binding sites between miR-141 and identified genes. Based on this, the seeding regions of each potential target was cloned upstream of the luciferase reporter gene in the pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HeLa cells pre-transfected with miR-141 overexpression vector, while increasing enormously in cells pre-transfected with miR-141 specific inhibitor.

Conclusion
Together, these data uncover an efficient miR-141-based mechanism that supports cervical cancer progression and identifies miR-141 as a credible therapeutic target.
How does the role of complementary and alternative medicine in general practice differ between countries? Interviews with doctors who have worked both in Germany and elsewhere in Europe
Authors: Linde Klaus , Bayer Robert , Gehrmann Jan , Jansky Bianca 
Published: September 2024

Abstract
Background
Available data suggest that general practitioners (GPs) in Germany use complementary and alternative medicine (CAM) modalities more frequently than GPs in many other countries. We investigated the country differences perceived by general practitioners who have worked in Germany and in one of four other European countries with regard to the role of complementary and alternative treatments in primary care.

Methods
In this qualitative study we conducted semi-structured interviews with 12 GPs who had worked both in Germany and Italy, the Netherlands, Norway or the United Kingdom (UK; n = 3 for each of the four countries). Participants were asked how they perceived and experienced country differences regarding health system, relevance of CAM modalities, the role of evidence-based medicine (EBM) and science, and how they handle so-called indeterminate situations. For the analysis, we followed a thematic analysis approach according to Braun and Clarke with focus on themes that cover CAM.

Results
Participants unanimously reported that they perceived CAM to be more relevant in general practice in Germany compared to the other countries. We identified four overarching themes in relation to the perceived reasons for these differences. Firstly, physicians with experiences in countries with a strong EBM and science orientation (Netherlands, Norway and the UK) considered the deeply ingrained view in national healthcare systems and GP communities that CAM modalities are not evidence-based as the main reason for the lower use of CAM by GPs. Secondly, extensive training of communication skills was cited as a reason that reduced the need for CAM in the Netherlands, Norway and the UK. Thirdly, differences in patient expectations and demands were perceived as a factor contributing to greater utilisation of CAM by German GPs compared to the other countries. Finally, country-specific reimbursement mechanisms were considered as a factor influencing the role of CAM in general practice.

Conclusions
The study results point to major differences between countries with regard to the role of CAM in GP care. Differences in basic attitudes in the discipline of general practice, patient expectations and system conditions appear to play an important role here.
Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT
Authors: Ku Eu Jeong , Kim Bongseong , Han Kyungdo , Lee Seung-Hwan , Kwon Hyuk-Sang 
Published: September 2024

Abstract
Background
The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated.

Methods
We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009–2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed.

Results
A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70–0.94), LEA (HR 0.76; 95% CI 0.60–0.96), and PAD (HR 0.81; 95% CI 0.68–0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles.

Conclusions
This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy.
Prevalence of child maltreatment in a nationwide sample of 18 to 31 year-olds in Germany
Authors: Kasinger Christoph , Schlack Robert , Brähler Elmar , Fegert Jörg M. , Clemens Vera 
Published: September 2024

Abstract
Background
Child maltreatment (CM) can have devastating and potentially lifelong effects for those affected and is a major contributor to mental health problems. To tackle public health problems it is crucial to have reliable data on CM. The aim of this study is to assess the prevalence and predictors of CM in a nationwide sample of the German population of young adults.

Methods
The study population (young adults aged 18 to 31 years) stems from the KiGGS Cohort study, the longitudinal branch of the German Health Interview and Examination Survey for children and adolescents. This sample meets the criteria of the United Nations Sustainable Development Goals (SDG) indicator 16.2.3. The data was collected between 2014 and 2017. CM were assessed with the Childhood Trauma Questionnaire (CTQ) in. In addition, socio-demographic variables and other known risk factors for CM were assessed. A total of 6433 (47.8% female) participants were included in the analyses. Binary logistic regression analyses were used to investigate predictors of maltreatment subtypes. Ordinal regression was used to examine their association with experience of multiple forms of CM.

Results
Overall, 18.4% (f: 20.9%, m: 16.1%) of the participants reported having experienced at least one type of CM; 6.7% (f: 8.8%, m: 4.8%) reported experiences of emotional abuse, 3.7% (f: 3.9%, m: 3.5%) physical abuse, 3.5% (f: 5.3%, m: 1.7%) sexual abuse, 9.0% (f: 9.9%, m: 8.2%) emotional neglect and 8.6% (f: 8.5%, m: 8.7%) physical neglect. Gender, subjective social status, education and household dysfunction (e.g. living with an individual who is using substances) emerged as significant predictors for different types of CM. Additionally, all these factors were significant risk factors for experiencing cumulative CM.

Conclusions
CM is common in the German population, with almost one in five people experiencing at least one type of CM. The results reveal important risk factors for the occurrence of CM. In particular, people with lower social status and those who grew up in dysfunctional households are at higher risk of CM. Greater support for this vulnerable population may reduce the prevalence of CM.
Simulated weightlessness procedure, head-down bed rest has reversible effects on the metabolism of rhesus macaque
Authors: Li Yuting , Zhang Xu , Xu Zhen , Chu Xixia , Hu Zhiqiang , Ye Zhengyang , Li Caiqin , Wang Zhenbo , Zeng Bin , Pan Jingyu , Zhao Qian , Zhou Chengbin , Lan Zhaohui , Kan Guanghan , He Guang , Xu Xiaodan , Li Weidong 
Published: September 2024

AbstractIt is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.
Repurposing of a library for high-content screening of inhibitors against Echinococcus granulosus
Authors: Zheng Weinan , Lv Gaofei , Li Jun , Zhang Yao , Qi Wenjing , Yan Mingzhi , Wu Jinzhi , Chan Chikin , Pan Xiaoben , Zhang Wenbao 
Published: September 2024

Abstract
Background
Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu lato (E. granulosus), with a worldwide distribution. The current treatment strategy for CE is insufficient. Limited drug screening models severely hamper the discovery of effective anti-echinococcosis drugs.

Methods
In the present study, using high-content screening technology, we developed a novel high-throughput screening (HTS) assay by counting the ratio of propidium iodide-stained dead protoscoleces (PSCs) to the total number of PSCs. In vitro and ex vivo cyst viability assays were utilized to determine the effect of drugs on cyst viability.

Results
Using the newly established HTS assay, we screened approximately 12,000 clinical-stage or The Food and Drug Administration (FDA)-approved small molecules from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library, as well as the LOPAC1280 and SelleckChem libraries, as a strategic approach to facilitate the drug discovery process. Initial screening yielded 173 compounds with anti-echinococcal properties, 52 of which demonstrated dose–response efficacy against E. granulosus PSCs in vitro. Notably, two agents, omaveloxolone and niclosamide, showed complete inhibition upon further validation in cyst and microcyst viability assays in vitro after incubation for 3 days, and in an ex vivo cyst viability assay using cysts isolated from the livers of mice infected with E. granulosus, as determined by morphological assessment.

Conclusions
Through the development of a novel HTS assay and by repurposing libraries, we identified omaveloxolone and niclosamide as potent inhibitors against E. granulosus. These compounds show promise as potential anti-echinococcal drugs, and our strategic approach has the potential to promote drug discovery for parasitic infections.

Graphical Abstract
Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma
Authors: Liu Yao-Ge , Jiang Shi-Tao , Zhang Jun-Wei , Zheng Han , Zhang Lei , Zhao Hai-Tao , Sang Xin-Ting , Xu Yi-Yao , Lu Xin 
Published: September 2024

AbstractHepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by difficulties in early diagnosis, prone to distant metastasis, and high recurrence rates following surgery. Extracellular vesicles (EVs) are a class of cell-derived particles, including exosomes, characterized by a phospholipid bilayer. They serve as effective carriers for intercellular communication cargo, including proteins and nucleic acids, and are widely involved in tumor progression. They are being explored as potential tumor biomarkers and novel therapeutic avenues. We provide a brief overview of the biogenesis and characteristics of EVs to better understand their classification standards. The focus of this review is on the research progress of EV-associated proteins in the field of HCC. EV-associated proteins are involved in tumor growth and regulation in HCC, participate in intercellular communication within the tumor microenvironment (TME), and are implicated in events including angiogenesis and epithelial-mesenchymal transition (EMT) during tumor metastasis. In addition, EV-associated proteins show promising diagnostic efficacy for HCC. For the treatment of HCC, they also demonstrate significant potential including enhancing the efficacy of tumor vaccines, and as targeting cargo anchors. Facing current challenges, we propose the future directions of research in this field. Above all, research on EV-associated proteins offers the potential to enhance our comprehension of HCC and offer novel insights for developing new treatment strategies.
Implementation of a rural emergency department-initiated buprenorphine program in the mountain west: a study protocol
Authors: Seliski Natasha , Madsen Troy , Eley Savannah , Colosimo Jennifer , Engar Travis , Gordon Adam , Barnett Christinna , Humiston Grace , Morsillo Taylor , Stolebarger Laura , Smid Marcela C , Cochran Gerald 
Published: September 2024

Abstract
Background
Opioid related overdose morbidity and mortality continue to significantly impact rural communities. Nationwide, emergency departments (EDs) have seen an increase in opioid use disorder (OUD)-related visits compared to other substance use disorders (SUD). ED-initiated buprenorphine is associated with increased treatment engagement at 30 days. However, few studies assess rural ED-initiated buprenorphine implementation, which has unique implementation barriers. This protocol outlines the rationale and methods of a rural ED-initiated buprenorphine program implementation study.

Methods
This is a two-year longitudinal implementation design with repeated qualitative and quantitative measures of an ED-initiated buprenorphine program in the rural Mountain West. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework outlines intervention assessments. The primary outcome is implementation measured by ED-initiated buprenorphine protocol core components. Reach, adoption, and maintenance are secondary outcomes. External facilitators from an academic institution with addiction medicine and prior program implementation expertise partnered with community hospital internal facilitators to form an implementation team. External facilitators provide ongoing support, recommendations, education, and academic detailing. The implementation team designed and implemented the rural ED-initiated buprenorphine program. The program includes OUD screening, low-threshold buprenorphine initiation, naloxone distribution and administration training, and patient navigator incorporation to provide warm hand off referrals for outpatient OUD management. To address rural based implementation barriers, we organized implementation strategies based on Expert Recommendations for Implementing Change (ERIC). Implementation strategies include ED workflow redesign, local needs assessments, ED staff education, hospital leadership and clinical champion involvement, as well as patient and community resources engagement.

Discussion
Most ED-initiated buprenorphine implementation studies have been conducted in urban settings, with few involving rural areas and none have been done in the rural Mountain West. Rural EDs face unique barriers, but tailored implementation strategies with external facilitation support may help address these. This protocol could help identify effective rural ED-initiated buprenorphine implementation strategies to integrate more accessible OUD treatment within rural communities to prevent further morbidity and mortality.

Trial Registration
ClinicalTrials.gov National Clinical Trials, NCT06087991. Registered 11 October 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT06087991.
Modeling regional occupancy of fishes using acoustic telemetry: a model comparison framework applied to lake trout
Authors: Futia Matthew H. , Binder Thomas R. , Henderson Mark , Marsden J. Ellen 
Published: September 2024

AbstractAcoustic telemetry is a common tool used in fisheries management to estimate fish space use (i.e., occupancy) from a local habitat scale to entire systems. Numerous analytical models have been developed to estimate different aspects of fish movement from telemetry datasets, yet evaluations of model performance and comparisons among models are limited. Here, we develop a framework to evaluate model estimates of regional occupancy in large and fragmented systems using an acoustic receiver array in Lake Champlain. We simulated the tracks of 100 acoustically tagged fish using a random walk function and created detection events based on receiver positions and distance-based detection probability. Regional occupancy for the simulated data was estimated by six movement models that ranged in analytical complexity, and results were compared to the true distributions for each simulated track to evaluate model error. The six movement models included: (1) a basic residency index using detections alone; (2) a residency index using last-observation-carried-forward; (3) a centers of activity model; (4) linear and non-linear interpolations (i.e., least-cost paths); and (5 and 6) two dynamic Brownian bridge movement models generated using separate packages in R. We developed a model selection process to compare model performance and select the optimal analysis based on simulation error. This process showed significant differences in model performance among the six movement models based on model error. Overall, the model generating least-cost paths using linear and non-linear interpolations consistently provided the most accurate regional occupancy estimates. Based on these simulation results, we applied this model to a case study that evaluated patterns in the regional distribution of stocked lake trout (Salvelinus namaycush) in Lake Champlain, which demonstrated distinct regional occupancy of two stocked lake trout groups. These results demonstrate potential for large variability in interpretation of acoustic telemetry data for describing regional fish distribution dependent on the analytical method used.
Evaluation of the drug-drug interactions management system for appropriate use of nirmatrelvir/ritonavir: a retrospective observational study
Authors: Tomida Takeshi , Kimura Takeshi , Yamamoto Kazuhiro , Uda Atsushi , Matsumoto Yuki , Tamura Naoki , Iida Masashi , Tanifuji Akiko , Matsumoto Kumiko , Mizuta Naomi , Ebisawa Kei , Ohji Goh , Omura Tomohiro , Iwata Kentaro , Yano Ikuko 
Published: September 2024

Abstract
Purpose
While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r.

Methods
A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality.

Results
This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1–3.1].

Conclusions
Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.