bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT1-mediated deacetylation of FOXO3 enhances mitophagy and drives hormone resistance in endometrial cancer
Authors: Wei Xuehua , Xiong Xiangpeng , Wang Pingping , Zhang Shufang , Peng Dongxian 
Published: September 2024

Abstract
Background
The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance.

Methods
High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues.

Results
High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein–protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC.

Conclusion
This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.
Identification of zinc finger MIZ-type containing 2 as an oncoprotein enhancing NAD-dependent protein deacetylase sirtuin-1 deacetylase activity to regulate Wnt and Hippo pathways in non-small-cell lung cancer
Authors: Gan Xueting , Feng Yuheng , Liu Yang , Lin Xuyong , Yu Xinmiao , Rong Xuezhu , Han Qiang 
Published: September 2024

Abstract
Background
Zinc finger MIZ-type containing 2 (ZMIZ2) can function as a coactivator and participate in the progression of certain malignant tumors; however, its expression and underlying molecular mechanism in non-small-cell lung cancer (NSCLC) remains unknown. In this study, we aim to analyze the expression of ZMIZ2 and its tumorigenic function in NSCLC, identifying its related factors.

Methods
ZMIZ2 expression in NSCLC tissue samples and cell lines was examined using immunohistochemistry and western blotting; its biological role was investigated using in vivo and in vitro assays. The association between ZMIZ2 and NAD-dependent protein deacetylase sirtuin-1 (SIRT1) was demonstrated using mass spectrometry and immunoprecipitation experiments. Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG)-based enrichment analysis, luciferase reporter assay, and real-time quantitative polymerase chain reaction (RT–qPCR) were conducted to verify the impact of ZMIZ2–SIRT1 combination on Hippo/Wnt pathways.

Results
ZMIZ2 was highly expressed in NSCLC and positively associated with advanced pTNM staging, lymph node metastasis, and poor overall survival. Functional experiments revealed that ZMIZ2 promotes the proliferation, migration, and invasiveness of lung cancer cells—establishing its role as a promoter of oncogenes. Molecular mechanism studies identified SIRT1 as an assisted key factor interacting with ZMIZ2. KEGG enrichment analysis revealed that ZMIZ2 is closely related to Wnt/Hippo pathways; ZMIZ2–SIRT1 interaction enhanced SIRT1 deacetylase activity. Direct downregulation of intranuclear β-catenin and yes-associated protein (YAP) acetylation levels occurred independently of upstream proteins in Wnt/Hippo pathways; transcriptional activities of β-catenin-transcription factor 4 (TCF4) and YAP–TEA domain family transcription factors (TEADs) were amplified.

Conclusions
ZMIZ2 promotes the malignant phenotype of lung cancer by regulating Wnt/Hippo pathways through SIRT1, providing an experimental basis for discovering novel biomarkers and developing tumor-targeted drugs.

Graphical Abstract
altAFplotter: a web app for reliable UPD detection in NGS diagnostics
Authors: Radtke Maximilian , Moch Johanna , Hentschel Julia , Schumann Isabell 
Published: September 2024

Abstract
Background
The detection of uniparental disomies (the inheritance of both chromosome homologues from a single parent, UPDs) is not part of most standard or commercial NGS-pipelines in human genetics and thus a common gap in NGS diagnostics. To address this we developed a tool for UPD-detection based on panel or exome data which is easy to use and publicly available.

Results
The app is freely available at https://altafplotter.uni-leipzig.de/ and implemented in Python, using the Streamlit framework for data science web apps. It utilizes bcftools and tabix for processing vcf files. The source code is available at https://github.com/HUGLeipzig/altafplotter and can be used to host your own instance of the tool.

Conclusion
We believe the app to be a great benefit for research and diagnostic labs, which struggle identifying and interpreting UPDs in their NGS diagnostic setup. The information provided allows a quick interpretation of the results and thus is suitable for usage in a high throughput manner by clinicians and biologists.
Recruiting people with selected citizenships for the health interview survey GEDA Fokus throughout Germany: evaluation of recruitment efforts and recommendations for future research
Authors: Koschollek Carmen , Gaertner Beate , Geerlings Julia , Kuhnert Ronny , Mauz Elvira , Hövener Claudia 
Published: September 2024

Abstract
Background
Germany is the second most common country of immigration after the US. However, people with own or familial history of migration are not represented proportionately to the population within public health monitoring and reporting. To bridge this data gap and enable differentiated analyses on migration and health, we conducted the health interview survey GEDA Fokus among adults with Croatian, Italian, Polish, Syrian, or Turkish citizenship living throughout Germany. The aim of this paper is to evaluate the effects of recruitment efforts regarding participation and sample composition.

Methods
Data collection for this cross-sectional and multilingual survey took place between 11/2021 and 5/2022 utilizing a sequential mixed-mode design, including self-administered web- and paper-based questionnaires as well as face-to-face and telephone interviews. The gross sample (n = 33436; age range 18–79 years) was randomly drawn from the residents’ registers in 120 primary sampling units based on citizenship. Outcome rates according to the American Association for Public Opinion Research, the sample composition throughout the multistage recruitment process, utilization of survey modes, and questionnaire languages are presented.

Results
Overall, 6038 persons participated, which corresponded to a response rate of 18.4% (range: 13.8% for Turkish citizenship to 23.9% for Syrian citizenship). Home visits accounted for the largest single increase in response. During recruitment, more female, older, as well as participants with lower levels of education and income took part in the survey. People with physical health problems and less favourable health behaviour more often took part in the survey at a later stage, while participants with symptoms of depression or anxiety more often participated early. Utilization of survey modes and questionnaire languages differed by sociodemographic and migration-related characteristics, e.g. participants aged 50 years and above more often used paper- than web-based questionnaires and those with a shorter duration of residence more often used a translated questionnaire.

Conclusion
Multiple contact attempts, including home visits and different survey languages, as well as offering different modes of survey administration, increased response rates and most likely reduced non-response bias. In order to adequately represent and include the diversifying population in public health monitoring, national public health institutes should tailor survey designs to meet the needs of different population groups considered hard to survey to enable their survey participation.
Comparison of a new MR rapid wash-out map with MR perfusion in brain tumors
Authors: Khadhraoui Eya , Schmidt Leon , Klebingat Stefan , Schwab Roland , Hernández-Durán Silvia , Gihr Georg , Paukisch Harald , Stein Klaus-Peter , Behme Daniel , Müller Sebastian Johannes 
Published: September 2024

Abstract
Background
MR perfusion is a standard marker to distinguish progression and therapy-associated changes after surgery and radiochemotherapy for glioblastoma. TRAMs (Treatment Response Assessment Maps) were introduced, which are intended to facilitate the differentiation of vital tumor cells and radiation necrosis by means of late (20–90 min) contrast clearance and enhancement. The differences of MR perfusion and late-enhancement are not fully understood yet.

Methods
We have implemented and established a fully automated creation of rapid wash-out (15–20 min interval) maps in our clinic. We included patients with glioblastoma, CNS lymphoma or brain metastases who underwent our MR protocol with MR perfusion and rapid wash-out between 01/01/2024 and 30/06/2024. Since both wash-out and hyperperfusion are intended to depict the active tumor area, this study involves a quantitative and qualitative comparison of both methods. For this purpose, we volumetrically measured rCBV (relative cerebral blood volume) maps and rapid wash-out maps separately (two raters). Additionally, we rated the agreement between both maps on a Likert scale (0–10).

Results
Thirty-two patients were included in the study: 15 with glioblastoma, 7 with CNS lymphomas and 10 with brain metastasis. We calculated 36 rapid wash-out maps (9 initial diagnosis, 27 follow-up).
Visual agreement of MR perfusion with rapid wash-out by rating were found in 44 ± 40% for initial diagnosis, and 75 ± 31% for follow-up. We found a strong correlation (Pearson coefficient 0.92, p < 0.001) between the measured volumes of MR perfusion and rapid wash-out. The measured volumes of MR perfusion and rapid wash-out did not differ significantly. Small lesions were often not detected by MR perfusion. Nevertheless, the measured volumes showed no significant differences in this small cohort.

Conclusions
Rapid wash-out calculation is a simple tool that provides new information and, when used in conjunction with MR perfusion, may increase diagnostic accuracy. The method shows promising results, particularly in the evaluation of small lesions.
RAS mutation associated with short surgically controllable period in colorectal liver metastases: a retrospective study
Authors: Ito Sono , Takamoto Takeshi , Nara Satoshi , Ban Daisuke , Mizui Takahiro , Nagata Hiroshi , Takamizawa Yasuyuki , Moritani Konosuke , Tsukamoto Shunsuke , Kanemitsu Yukihide , Kinugasa Yusuke , Esaki Minoru 
Published: September 2024

Abstract
Background
The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability.

Methods
This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP.

Results
A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03).

Conclusions
CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP.
Interactions of depression, anxiety, and sleep quality with menopausal symptoms on job satisfaction among middle-aged health workers in England: a STROBE-based analysis
Authors: Asiamah Nestor , Cronin Camille , Abbott Joanne E. , Smith Susan 
Published: September 2024

Abstract
Background
This study examined the association between menopausal symptoms and job satisfaction, and ascertained whether three psychosomatic factors (e.g., anxiety, depression, and sleep quality) interact with menopausal symptoms on job satisfaction.

Methods
A cross-sectional design with sensitivity analysis was adopted. The participants of the study were clinical health workers in England. Data from 154 health workers were analyzed with the hierarchical linear regression (HLR) analysis.

Results
There was a negative association between menopausal symptoms and job satisfaction (β = −0.38; t = −4.81, p < 0.001), but this relationship became non-significant after adjusting for work stress, self-reported health, job tenure, and resilience at work. An interaction between menopausal symptoms and the psychosomatic factors was found. The strength of the negative association between menopausal symptoms and job satisfaction was weakened by sleep quality (β = 0.05; t = 0.48; p > 0.05) but was strengthened by anxiety (β = −0.22; t = −2.28; p < 0.05) and depression (β = −0.24; t = −2.16; p < 0.05).

Conclusion
Menopausal symptoms can be directly associated with lower job satisfaction and indirectly associated with lower job satisfaction through its interaction with depression and anxiety. Menopausal symptoms can weaken the positive association between sleep quality and job satisfaction.
Sex-specific chrono-nutritional patterns and association with body weight in a general population in Spain (GCAT study)
Authors: Pons-Muzzo Luciana , de Cid Rafael , Obón-Santacana Mireia , Straif Kurt , Papantoniou Kyriaki , Santonja Isabel , Kogevinas Manolis , Palomar-Cros Anna , Lassale Camille 
Published: September 2024

Abstract
Background
Altered meal timing patterns can disrupt the circadian system and affect metabolism. Our aim was to describe sex-specific chrono-nutritional patterns, assess their association with body mass index (BMI) and investigate the role of sleep in this relationship.

Methods
We used the 2018 questionnaire data from the population-based Genomes for Life (GCAT) (n = 7074) cohort of adults aged 40–65 in Catalonia, Spain, for cross-sectional analysis and its follow-up questionnaire data in 2023 (n = 3128) for longitudinal analysis. We conducted multivariate linear regressions to explore the association between mutually adjusted meal-timing variables (time of first meal, number of eating occasions, nighttime fasting duration) and BMI, accounting for sleep duration and quality, and additional relevant confounders including adherence to a Mediterranean diet. Finally, cluster analysis was performed to identify chrono-nutritional patterns, separately for men and women, and sociodemographic and lifestyle characteristics were compared across clusters and analyzed for associations with BMI.

Results
In the cross-sectional analysis, a later time of first meal (β 1 h increase = 0.32, 95% CI 0.18, 0.47) and more eating occasions (only in women, β 1 more eating occasion = 0.25, 95% CI 0.00, 0.51) were associated with a higher BMI, while longer nighttime fasting duration with a lower BMI (β 1 h increase=-0.27, 95% CI -0.41, -0.13). These associations were particularly evident in premenopausal women. Longitudinal analyses corroborated the associations with time of first meal and nighttime fasting duration, particularly in men. Finally, we obtained 3 sex-specific clusters, that mostly differed in number of eating occasions and time of first meal. Clusters defined by a late first meal displayed lower education and higher unemployment in men, as well as higher BMI for both sexes. A clear “breakfast skipping” pattern was identified only in the smallest cluster in men.

Conclusions
In a population-based cohort of adults in Catalonia, we found that a later time of first meal was associated with higher BMI, while longer nighttime fasting duration associated with a lower BMI, both in cross-sectional and longitudinal analyses.
Pareto-principle in rare disease education: assessing the representation of common rare diseases in medical education and coding systems
Authors: Berger Alexandra , Grimm Kai Lars , Noll Richard , Wagner Thomas OF 
Published: September 2024

Abstract
Background
The Pareto Principle asserts that a large portion of results can be achieved with a small amount of effort. Wakap et al. found that around 80% of individuals with rare diseases (RD) suffer from one of 149 specific rare diseases. A significant challenge in the RD domain is the lack of information, compounded by the fact that most RD are not specifically codifiable in the ICD-10, leading to a deficit in reliable epidemiological data. Additionally, time constraints in medical education hinder the comprehensive teaching of all RD, contributing to the diagnostic odyssey problem through failure of recognizing diseases. We identified the most and second most prevalent RD (prevalences of 1–5/10,000 and 1–9/100,000, respectively) from the Orphanet Epidemiology File, totaling 454 diseases. We investigated the feasibility of specific coding using ICD-10-GM and whether these diseases were explicitly listed in the subject catalog (GK) of the second state examination in human medicine in Germany. A two-sided chi-square test was employed to identify statistically significant differences between prevalence groups.

Results
Out of 454 diseases, a total of 34% could be specifically coded in ICD-10-GM, with 49% of diseases in the 1–5/10,000 prevalence range (153 RD) and 26% in the 1–9/100,000 range (301 RD) having specific codes. Approximately 15% of all investigated diseases were part of the GK, with 25% of the most prevalent and 10% of the second most prevalent RD group, respectively. Statistically significant differences were observed between prevalence groups concerning the presence of a specific ICD-10-GM code and inclusion in the GK.

Conclusion
Only 49% of the most prevalent RD can be specifically coded, highlighting the challenge of limited epidemiological data on RD. In Germany, the Alpha-ID was introduced in addition to ICD-10 in the inpatient setting to obtain more valid epidemiological data on RD. Recognizing the Pareto Principle’s applicability, the study emphasizes the importance of including the most common rare diseases in medical education. While recognizing the limitations, especially in covering ultra-rare diseases, the study underscores the potential benefits of enhancing medical curricula to improve rare disease awareness and diagnostic accuracy.
Owner satisfaction and prognosis for return to work after pancarpal arthrodesis in working dogs in the United Kingdom: a retrospective study (2011–2020)
Authors: Higgins Joseph , Hayes Graham 
Published: September 2024

Abstract
Background
Pancarpal arthrodesis (PCA) is a commonly performed procedure in the UK. However, it is not known whether working dogs in the UK and other European countries with carpal injuries that have undergone unilateral PCA are able to return to working ability as determined by the owner. Medical records from a referral hospital in the UK were reviewed retrospectively for cases of working dogs treated using unilateral PCA. Case files and radiographs were retrospectively analysed for cause of injury, diagnosis, and complications. The ability of the dog to work after surgery and owner satisfaction with the outcome were assessed using telephone questionnaire.

Results
50% (5/10, 50%) owners stated their dog could perform normal duties, 4/10 (40%) could perform most duties with some allowances. Outcome was not as good for dogs working on steep, uneven fell terrain. 80% (8/10, 80%) owners rated the level of post-operative lameness as unaffected with a normal gait. 90% (9/10, 90%) owners were either very satisfied or satisfied with the outcome of the procedure, and 90% owners stated the financial investment was worthwhile.

Conclusions
Unilateral PCA carries a good prognosis for working dogs with high owner satisfaction. Caution should be advised for dogs expected to work on steep, uneven fell terrain.
Should AI models be explainable to clinicians?
Authors: Abgrall Gwénolé , Holder Andre L. , Chelly Dagdia Zaineb , Zeitouni Karine , Monnet Xavier 
Published: September 2024

AbstractIn the high-stakes realm of critical care, where daily decisions are crucial and clear communication is paramount, comprehending the rationale behind Artificial Intelligence (AI)-driven decisions appears essential. While AI has the potential to improve decision-making, its complexity can hinder comprehension and adherence to its recommendations. “Explainable AI” (XAI) aims to bridge this gap, enhancing confidence among patients and doctors. It also helps to meet regulatory transparency requirements, offers actionable insights, and promotes fairness and safety. Yet, defining explainability and standardising assessments are ongoing challenges and balancing performance and explainability can be needed, even if XAI is a growing field.