bluuebunny/crossref_metadata_2025_split huggingface dataset:
ER-anchored protein sorting controls the fate of two proteasome activators for intracellular organelle communication during proteotoxic stress
Authors: Üstün Suayib , Langin Gautier , Raffeiner Margot , Biermann David , Franz-Wachtel Mirita , Spinti Daniela , Börnke Frederik , Macek Boris 
Published: March 2024

Abstract

Proteotoxic stress, characterized by the accumulation of damaged proteins, poses a significant challenge to cellular homeostasis. To mitigate proteotoxicity eukaryotes employ the proteasome that is regulated by proteasome activators, e.g. transcription factors that promote gene expression of proteasome subunits. As proteotoxicity originates in different compartments, cells need to perceive signals from various locations. Understanding which components integrate signals to address proteotoxicity is essential to develop strategies to cope with proteotoxicity but remain elusive. Here, we identify that the proteasome autoregulatory feedback loop acts as a gatekeeper to facilitate the communication between nucleus and chloroplast. We reveal that the ER-anchored protein sorting system (ERAPS) controls the proteasomal degradation or nuclear translocation of proteasome activators NAC53 and NAC78. While both transcription factors activate the proteasome gene expression, they repress photosynthesis-associated nuclear genes during proteotoxicity through association with a conserved cis-element. Our data implicate a general trade-off between proteasome function and energy metabolism unravelling an unprecedented mechanism of how eukaryotic cells cope with proteotoxicity. Collectively, our discoveries provide a novel conceptual framework in which the proteasome autoregulatory feedback loop coordinates subcellular proteostasis and the trade-off between growth and defence.
Sugar sweetened beverages consumption is associated with metabolic alterations in an independent manner of body mass index and body fat in young population.
Authors: Anaya-Loyola Miriam Aracely , Camacho-Calderon Nicolás , Villagran-Herrera María Elena , Lopez-Velazquez María Guadalupe , Aguilar-Galarza Adriana , Palacios-Delgado Jorge , Campos-Ramírez Cesar 
Published: March 2024

Abstract

Background Sugar sweetened beverages (SSBs) consumption are widely associated with metabolic and anthropometric dysfunctions. The aim of this study was to examine the relationship between SSBs consumption and its attributable caloric intake with metabolic and anthropometric variables. We hypothesize that SSBs consumption is positively associated with metabolic dysfunction independently of the body composition.
Methods A cross-sectional analysis was carried out in healthy university students, information was collected on metabolic and anthropometric measurements using standardized procedures as well as SSBs consumption patterns through validated questionnaire to describe associations and interactions.
Results A total of 504 students, 208 men (41.3%) and 296 women (58.7%), with an average age of 19.0 years (SD = 1.5), were evaluated. The 35.4% of men and 32.6% of women presented body mass index (BMI) ≥ 25 kg / m2. The average SSBs consumption was 20.3 servings / week (SD = 14.0). A positive association was found between SSBs consumption and the concentrations of triglycerides (TG), low-density lipoprotein cholesterol (LDL- C) and total cholesterol (TC) in men, while women presented a positive association with visceral fat and LDL. Men consume more calories than women with an average of 2174.9 kcal / week (SD = 1380.0) from SSBs and 1526.9 kcal / week (SD = 1070.3) respectively (p <0.01). The general linear model do not show interactions between the body fat or the obesity diagnosis and the SSBs consumption for the variables TC, TG and LDL-C in men and very low density lipoprotein in women.
Conclusion This study shows that the concentrations of the metabolic variables seem to be associated with the SSBs consumption independently of obesity or body fat.
Temporal Single-Cell Sequencing Analysis Reveals That GPNMB-Expressing Macrophages Potentiate Muscle Regeneration
Authors: Chen Yu-Fan 
Published: March 2024

Abstract
Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poorly understood. To address this issue, we induced injury and performed single-cell RNA sequencing on individual cells in skeletal muscle at different time points. Our analysis revealed a distinct macrophage subset that expressed high levels of Gpnmb and that coexpressed critical factors involved in macrophage-mediated muscle regeneration, including Igf1, Mertk, and Nr1h3. Gpnmb gene knockout inhibited macrophage-mediated efferocytosis and impaired skeletal muscle regeneration. Functional studies demonstrated that GPNMB acts directly on muscle cells in vitro and improves muscle regeneration in vivo. These findings provide a comprehensive transcriptomic atlas of macrophages during muscle injury, highlighting the key role of the GPNMB macrophage subset in regenerative processes. Targeting GPNMB signaling in macrophages could have therapeutic potential for restoring skeletal muscle integrity and homeostasis.
Metabolites mediate the causal associations between gut microbiota and NAFLD：a Mendelian randomization study
Authors: Ouyang Chen , Liu Pengpeng , Liu Yiwei , Lan Jianwei , Liu Quanyan 
Published: March 2024

Abstract

Background
Although gut microbiota and serum metabolite composition have been observed to be altered in patients with non-alcoholic fatty liver disease (NAFLD), previous observational studies have demonstrated inconsistent results. As this may be influenced by factors such as confounders and reverse causality, we used Mendelian randomization to clarify the causal effect of gut microbiota and blood metabolites on NAFLD.
Methods
In this research, we performed a two-step Mendelian randomization analysis by utilizing genome-wide association study (GWAS) data obtained from MiBioGen and UK Biobank. To mitigate potential errors, we employed False Discovery Rate (FDR) correction and linkage unbalanced regression (LDSC) analysis. Sensitivity analyses including cML-MA and bidirectional Mendelian randomization were performed to ensure the robustness of the results.
Results
In this study, a total of nine gut microbiota and seven metabolites were found to be significantly associated with NAFLD. MR analysis of the above findings revealed a causal relationship between Ruminococcus2 and cysteine-glutathione disulfide (OR = 1.17, 95%CI = 1.006–1.369, P = 0.041), as well as 3-indoleglyoxylic acid (OR = 1.18, 95%CI = 1.011–1.370, P = 0.036). For each incremental standard deviation in Ruminococcus2 abundance, there was a corresponding 26% reduction in NAFLD risk (OR = 0.74, 95%CI = 0.61–0.89, P = 0.0012), accompanied by a 17% increase in cysteine-glutathione disulfide levels (OR = 1.17, 95%CI = 1.01–1.37, P = 0.041) and an 18% increase in 3-indoleglyoxylic acid levels (OR = 1.18, 95%CI = 0.81-1.00, P = 0.036). The proportion mediated by cysteine-glutathione disulfide is 11.2%, while the proportion mediated by 3-indoleglyoxylic acid is 7.5%.
Conclusion
Our study suggests that increased abundance of specific gut microbiota may reduce the risk of developing NAFLD, and this relationship could potentially be mediated through blood metabolites.
Ectopic expression of chemokines and chemokine receptors in relation to immune cell infiltration, prostate cancer recurrence
Authors: Zhang Jialong , Huang Cong , Wang Hongzhi 
Published: March 2024

Abstract
Background
Interleukins can nurture a tumor promoting environment and simultaneously regulate immune cell infiltration. However, the potential roles of interleukins in the prostate cancer immune landscape remain abstruse.
Methods
We comprehensively investigated the interleukin expression patterns and tumor immune landscape of prostate cancer patients. And explored the interleukin expression patterns with immune infiltration landscape. The interleukin score was established using LASSO cox regression analysis. Multivariate Cox regression analysis was employed to assess the prognostic value of the interleukin score.
Results
We identified two distinct interleukin clusters, characterized by different immune cell infiltration, tumor promoting signaling pathways activation and prognosis. The interleukin score was established to estimate the prognosis of individual prostate cancer patient. Further analysis demonstrated that the interleukin score was an independent prognostic factor of PRAD. Finally, we investigated the predictive value of interleukin score in the programed cell death protein (PD-1) blockade therapy of patients with prostate cancer.
Conclusions
This study demonstrated the correlation between interleukin and tumor immune landscape in prostate cancer. The comprehensive evaluation of interleukin expression patterns in individual prostate patients contribute to our understanding of the immune landscape and helps clinicians selecting proper immunotherapy strategies for prostate patients.
The Effect of Selinexor on Prostaglandin Synthesis in Virus-Positive Merkel Cell Carcinoma Cell Lines
Authors: Narayanan Deepika , Bartley Brooke , Landes Jennifer , Moore Stephen A. , Kulkarni Veda , He Qin , Simonette Rebecca , Doan Hung Q. , Rady Peter L. , Tyring Stephen K. 
Published: March 2024

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with high rates of metastasis and mortality. In vitro studies suggest that selinexor (KPT-330), an inhibitor of exportin 1, may be a targeted therapeutic option for MCC. This selective inhibitor prevents the transport of oncogenic mRNA out of the nucleus. Of note, 80% of MCC tumors are integrated with Merkel cell polyomavirus (MCPyV), and virally encoded tumor-antigens, small T (sT) and large T (LT) mRNAs may require an exportin transporter to relocate to the cytoplasm and modulate host tumor-suppressing pathways. To explore selinexor as a targeted therapy for MCC, we examine its ability to inhibit LT and sT antigen expression in vitro and its impact on the prostaglandin synthesis pathway. Protein expression was determined through immunoblotting and quantified by densitometric analysis. Statistical significance was determined with t-test. Treatment of MCPyV-infected cell lines with selinexor resulted in a significant dose-dependent downregulation of key mediators of the prostaglandin synthesis pathway. Given the role of prostaglandin synthesis pathway in MCC, our findings suggest that selinexor, alone or in combination with immunotherapy, could be a promising treatment for MCPyV-infected MCC patients who are resistant to chemotherapy and immunotherapy.
Early Prognosis Prediction for Non-variceal Upper Gastrointestinal Bleeding in the Intensive Care Unit: Based on Interpretable Machine Learning
Authors: Zhao Xiaoxu , Wei Shuxing , Pan Yujie , Qu Kunlong , Yan Guanghao , Wang Xiya , Song Yuguo 
Published: March 2024

Abstract

Introduction: This study aims to construct a mortality prediction model for patients with non-variceal upper gastrointestinal bleeding (NVUGIB) in the intensive care unit (ICU), employing advanced machine learning algorithms. The goal is to identify high-risk populations early, contributing to a deeper understanding of patients with NVUGIB in the ICU.Methods: We extracted NVUGIB data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.2) database spanning from 2008 to 2019. Feature selection was conducted through LASSO regression, followed by training models using eleven machine learning methods. The best model was chosen based on the area under the curve (AUC). Subsequently, Shapley additive explanations (SHAP) was employed to elucidate how each factor influenced the model. Finally, a case was randomly selected, and the model was utilized to predict its mortality, demonstrating the practical application of the developed model.Results: In total, 2716 patients with NVUGIB were deemed eligible for participation. Following selection, 30 out of a total of 64 clinical parameters collected on day 1 after ICU admission remained associated with prognosis and were utilized for developing machine-learning models. Among the eleven constructed models, the Gradient Boosting Decision Tree (GBDT) model demonstrated the best performance, achieving an AUC of 0.853 and an accuracy of 0.839 in the validation cohort. Feature importance analysis highlighted that Shock, Glasgow Coma Scale (GCS), renal disease, age, albumin, and alanine aminotransferase (ALP) were the top six features of the GBDT model with the most significant impact. Furthermore, SHAP force analysis illustrated how the constructed model visualized the individualized prediction of death.Conclusions: Patient data from the MIMIC database were leveraged to develop a robust prognostic model for patients with NVUGIB in the ICU. The analysis using SHAP also assisted clinicians in gaining a deeper understanding of the disease.
Causal Relationship between the Gut Microbiota and Haematological Malignancies: A Two-Sample Mendelian Randomization Analysis
Authors: Xiang Biyu , Li Qianyuan , Zhang Hongfei , JI Shuqi , Peng Yuzhen , Yao Chenjiao 
Published: March 2024

Abstract

Background
The gut microbiota has been implicated in the occurrence and development of haematological malignancies. However, the causal relationship between specific gut microbiota and haematological malignancies remains unclear.
Methods
In this study, we employed the Mendelian randomization (MR) approach to investigate the causal relationship between the gut microbiota and haematological malignancies. We selected the human gut microbiota as the exposure variable from the human whole-genome association analysis (GWAS) dataset of International Alliance MiBioGen. GWAS data of eight haematological malignancies from the FinnGen database were used as the outcome. We performed two-sample Mendelian randomization analysis using inverse-variance weighting (IVW), the weighted median estimator (WME), and MR‒Egger. Sensitivity analysis was also conducted to assess the stability of all MR results.
Results
Our findings revealed that 57 gut microbiota species may be causally related to haematological malignancies. Specifically, the family Oxalobacteraceae (OR = 1.828, 95% CI = 1.284 to 2.602, p = 0.0008) exhibited a strong positive correlation with the occurrence of ML. Additionally, the presence of the class Erysipelotrichia (OR = 8.738, 95% CI = 2.469 to 30.930, p = 0.001), the order Erysipelotrichales (OR = 8.738, 95% CI = 2.469 to 30.930, p = 0.001), and the family Erysipelotrichaceae (OR = 8.738, 95% CI = 2.469 to 30.930, p = 0.001) exhibited strong positive correlations with the occurrence of MCL. On the other hand, the class Methanobacteria (OR = 0.525, 95% CI = 0.338 to 0.816, p = 0.004), order Methanobacteriales (OR = 0.525, 95% CI = 0.338 to 0.816, p = 0.004), and family Methanobacteriaceae (OR = 0.525, 95% CI = 0.338 to 0.816, p = 0.004), as well as the class Actinobacteria(OR = 0.394, 95% CI: 0.209 to 0.746, p = 0.004), and genus Lachnospiraceae UCG001 (OR = 0.411, 95% CI = 0.232 to 0.728, p = 0.002), exhibited strong negative correlations with the occurrence of mature NK/T-cell lymphoma. These results suggest that the gut microbiota may play a significant role in the development of haematological malignancies.
Conclusions
Our findings suggest a causal relationship between the gut microbiota and haematological malignancies, which may contribute to providing new insights into the mechanisms of microbiota-mediated hematological malignancies. Additionally, these findings might lead to the identification of risk factors and early prediction of haematological malignancies.
Purity Control of Simulated Moving Bed Based on Advanced Fuzzy Controller
Authors: xie chaofan , Zhang Hong , Chen Xiong 
Published: March 2024

Abstract

Simulated Moving Bed (SMB) technology is considered one of the most successful techniques for chromatographic separation. However, due to its complex model and sensitivity to numerous separation performance parameters, controlling SMB systems poses challenges. In recent years, the application of fuzzy controllers in industrial settings has gained popularity due to their simplicity and robust performance. Nevertheless, the traditional fuzzy controllers used in industry often neglect the consideration of error acceleration, leading to a slight deviation from the target value in steady-state conditions and oscillatory behavior when system parameters change. This study proposes the implementation of an advanced fuzzy controller for controlling purity in simulated moving bed systems, and it demonstrates improved robustness compared to traditional fuzzy control methods.
Using digital technology as a platform to strengthen the continuum of care at community level for maternal, child and adolescent health in Tanzania: Introducing the Afya-Tek program
Authors: Dillip Angel , Kahamba Gloria , Sambaiga Richard , Shekalaghe Elizabeth , Kapologwe Ntuli , Kitali Erick , Kengia James Tumaini , Haonga Tumaini , Nzilibili Simon , Tanda Mark , Haroun Yasini , Hofmann Rachel , Litner Rebecca , Lampariello Riccardo , Kimatta Suleiman , Ketende Sosthenes , James Johanitha , Fumbwe Khadija , Mahmoud Fatma , Lugumamu Oscar , Gabunda Christina , Salim Ally , Allen Megan , Mathew Eden , Nkaka Melania , Liana Jafary , Norman Toby , Mbwasi Romuald , Sarkar Nandini 
Published: March 2024

Abstract

Poor quality of care within Tanzania’s primary health system contributes to thousands of preventable maternal and child deaths, and unwanted pregnancies each year. A key contributor is lack of coordination between three primary healthcare actors: public sector Community Health Workers (CHWs) and health facilities, and private sector Accredited Drug Dispensing Outlets (ADDOs). The Afya-Tek program aims to improve the continuity of care amongst these actors in Kibaha district, through a mobile-application based digital referral system that focuses on improving maternal, child and adolescent health. The digital system called Afya-Tek was co-created with users and beneficiaries, and utilises open-source technology in-line with existing government systems. The system guides healthcare actors with individualised decision support during client visits and recommends accurate next steps (education, treatment, or referral). From July 2020 to June 2023, a total of 241,000 individuals were enrolled in the Afya-Tek program covering 7,557 pregnant women, 6,582 postpartum women, 45,900 children, and 25,700 adolescents. CHWs have conducted a total of 626,000 home visits to provide health services, including screening clients for danger signs. This has resulted in 38,100 referrals to health facilities and 24,300 linkages to ADDOs. At the ADDO level, 48,552 clients self-presented; 33% of children with pneumonia symptoms received Amoxicillin; 34% of children with diarrhoea symptoms received ORS and zinc; and 4,203 referrals were made to nearest health facilities. Adolescents preferred services at ADDOs as a result of increased perceived privacy and confidentiality. In total, 89% of all referrals were attended by health facilities. As the first digital health program in Tanzania to demonstrate the linkage among public and private sector primary healthcare actors, Afya-Tek holds promise to improve maternal, child and adolescent health as well as for scale-up and sustainability, through incorporation of other disease conditions and integration with government’s Unified Community System (UCS).
Effect of concentrated growth factor(CGF) on postoperative patient comfort in impacted lower third molars undergoing coronectomy: a prospective clinical study
Authors: Dudak Muharrem Ergun , Calis Aylin , Koca Huseyin 
Published: March 2024

Abstract

Objectives The aim of this study was to evaluate the effect of CGF on post-operative patient comfort following coronectomy in impacted third molars with roots associated with the nervus alveolaris inferior.
Materials and Methods Thirty-five patients with bilateral vertical impacted wisdom teeth with roots associated with the nervus alveolaris inferior were included in the study with an indication for coronectomy. Coronectomy was performed on both sides followed by cgf on one side. Pain levels were monitored with the VAS scale for 7 post-operative days. In addition, the amount of edema occurring on post-operative days 2 and 7 was also measured. All data were statistically evaluated. Statistical significance was determined as p<0.001.
Results The first 6 days showed significantly lower (p<0.001) pain on the CGF-treated side, while the difference between the sides was not significant on the 7th day (p=0.627). On the 2nd day, significantly lower (p<0.001) edema occurred in the tragus-pogonion and angulus-lateral canthus planes on the CGF treated side. On day 7, there was no significant difference in edema between the sides. Uneventful healing was observed in all patients.
Conclusion It is possible to prevent possible nerve damage with coronectomy. In addition, CGF can successfully improve patient comfort in the early post-operative period.
Clinical Relevance Post-operative pain and edema, which are very important for patients, can be significantly reduced with the application of CGF, an easily obtainable autogenous product. The results obtained may provide valuable contributions to clinicians.
Analysing Roman itineraries using the GIS tool: the case of the road XIX
Authors: Argüelles-Alvarez Patricia Ana , Trapero-Fernández Pedro 
Published: March 2024

Abstract
Reconstruction of the Roman road network must be approached from various methodologies of multidisciplinary character. When traditional approaches have been exhausted without achieving a historiographical consensus, the problem may appear insurmountable. However, leveraging Geographic Information Systems (GIS) provides an avenue for re-evaluating existing proposals and suggesting more fitting layouts. This can be accomplished through a meticulous analysis that incorporates topographic and non-Euclidean correlations, allowing for a more nuanced and accurate understanding of the subject matter than conventional methods might offer. We explore a case study in the Galician territory, where we have detected methodological shortcomings when it comes to being able to identify and reconstruct the route of the XIX road: Item Bracaram Asturicam. One of the sections that has aroused the most debate is the case of Tude to Lucus Augusti, based on several basic problems that are the identification of the mansions, the lack of consensus in the measurements of the distances of the miles referred to in the classical sources, and the complex orography of this territory. To propose answers and theories that solve the current problem of the description of this route of the XIX road, it is proposed a work that, through applications of Geographic Information Systems, settles the debate of the current state of the question.