bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Parkinson’s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons
Authors: Jones-Tabah Jace , He Kathy , Karpilovsky Nathan , Senkevich Konstantin , Deyab Ghislaine , Pietrantonio Isabella , Goiran Thomas , Cousineau Yuting , Nikanorova Daria , Goldsmith Taylor , del Cid Pellitero Esther , Chen Carol X.-Q. , Luo Wen , You Zhipeng , Abdian Narges , Ahmad Jamil , Ruskey Jennifer A. , Asayesh Farnaz , Spiegelman Dan , Fahn Stanley , Waters Cheryl , Monchi Oury , Dauvilliers Yves , Dupré Nicolas , Miliukhina Irina , Timofeeva Alla , Emelyanov Anton , Pchelina Sofya , Greenbaum Lior , Hassin-Baer Sharon , Alcalay Roy N. , Milnerwood Austen , Durcan Thomas M. , Gan-Or Ziv , Fon Edward A. 
Published: November 2024

Abstract
Background
Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson’s disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified.

Methods
Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines, induced pluripotent stem cell-derived dopaminergic neurons and midbrain organoids and assessed lysosomal activity and the handling of aggregated synuclein fibrils.

Results
We find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. In cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. In midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein.

Conclusions
These results indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.
Network analysis of influential risk factors in adolescent suicide attempters
Authors: Fernandez-Fernandez Jennifer , Jiménez-Treviño Luis , Andreo-Jover Jorge , Ayad-Ahmed Wala , Bascarán Teresa Bobes , Canal-Rivero Manuel , Cebria Annabel , Crespo-Facorro Benedicto , De la Torre-Luque Alejandro , Diaz-Marsa Marina , Gonzalez-Pinto Ana , Gomez Sandra , Grande Iría , Iglesias Noelia , Ortin Francisco , March Katya , Palao Angela , Pérez-Díez Iván , Pérez-Guerra Carla , Ruiz-Veguilla Miguel , Vieta Eduard , Perez-Sola Victor , Saiz Pilar Alejandra 
Published: November 2024

Abstract
Objective
This study aims to investigate the interrelationship of risk factors for suicidal behaviour and their influence on attempt severity in a sample of adolescents who have recently attempted suicide. For it a network analyse was performed.

Method
Data from a sample of adolescents from 12 to 17 years of age with documented suicide attempts were collected and analysed in the context of a larger study conducted in Spain called SURVIVE. Several factors were examined including age, sex, depression, trauma, impulsivity, and substance abuse. Graph analysis was performed to identify relationships and centrality measures among these factors.

Results
A total of 267 participants were enrolled: 233 females and 34 males with a mean age of 15.00 years (SD = 1.52). The results indicate that age and sex do not have a notable relationship with attempt severity in adolescents. Emotional and behavioural difficulties, measured by the Strengths and Difficulties Questionnaire (SDQ), have the greatest influence on other variables. Depression and childhood trauma show varying degrees of association with suicidal behaviour, as does motor impulsivity. Substance use does not appear to be strongly related to suicide attempt severity. The number of suicide attempts is strongly correlated with emotional and behavioural difficulties, depression, and childhood trauma. Lethality of suicide attempts and intensity of suicidal ideation do not show significant associations with the other variables.

Conclusion
This study identifies significant risk factors for adolescent suicide. Emotional and behavioural symptoms, depression, and childhood trauma are strongly linked to suicidal behaviour. However, age, sex, and substance abuse show minimal correlation. Assessing emotional difficulties and depressive symptoms using specific questionnaires could be crucial in evaluating suicidal behaviour in adolescents.
Reducing Exposures to Endocrine Disruptors (REED) study, a personalized at-home intervention program to reduce exposure to endocrine disrupting chemicals among a child-bearing age cohort: study protocol for a randomized controlled trial
Authors: Rochester Johanna R. , Kwiatkowski Carol F. , Lathrop Michael Kupec , Neveux Iva , Daza Eric J. , Grzymski Joseph , Hua Jenna 
Published: November 2024

Abstract

Background

Exposures to endocrine disrupting chemicals (EDCs) have been linked to chronic diseases including breast cancer, metabolic syndrome, diabetes, and infertility. Exposure during pregnancy may have a lifelong impact on the fetus. Services are needed to allow individuals to learn about their personal EDC exposures and how to reduce them. Million Marker (MM) aims to crowdsource and scale the biomonitoring of environmental chemicals and provide actionable results to empower individuals to proactively assess, track, and reduce their EDC exposures. In previous research, we developed and tested the first mobile EDC intervention service (mail-in urine testing and exposure report-back) for its efficacy in increasing EH literacy (EHL), willingness to reduce exposures (i.e., readiness to change, RtC), and system usability. After intervention, we found increased EHL, increased RtC in women (but not men), and decreased EDC exposure. However, some participants did not increase their RtC and had difficulty carrying out the intervention on their own. The reasons for these less optimal results were the difficulty in the EHL subject matter—participants still felt ill-prepared to apply their knowledge to making healthier lifestyle changes. Therefore, in this study, we will address these perceived limitations.

Methods
We will test a self-directed online interactive curriculum with live counseling sessions and individualized support modeled after the highly effective Diabetes Prevention Program (DPP). Recruiting from the Healthy Nevada Project (HNP), one of the largest population health cohorts in the world, we test the effectiveness of our EDC-specific online intervention curriculum via EHL and RtC surveys and determine changes in EDC exposure before and after intervention in a randomized controlled trial. We will also test for common clinical biomarkers via a commercially available at-home test (Siphox). We will recruit and randomize 300 women and 300 men of reproductive age (total n=600) from HNP. Our target population is men and women of reproductive age (18–44 years old).

Discussion
At the conclusion of this project, we will be well-positioned to scale our services to clinics and the general public, with the eventual aims of FDA approval, insurance coverage, and incorporation into routine clinical care.
Assessment of wind energy potential along the Egyptian Mediterranean Coast
Authors: Tonbol Kareem , Elbessa Mohamed , Ibrahim Omneya , El-Geziry Tarek M. 
Published: November 2024

Abstract
Background
Currently, there is no wind park operating along the Egyptian Mediterranean Coast. Therefore, this study aims to find suitable locations for such projects. Wind data from five coastal meteorological stations were used. These are Marsa Matruh (MM), Ras El-Tin (RE), Abu Qir (AQ), Port Said (PS), and Arish (Ar), in that order from west to east. The wind regime dataset, comprising velocity and direction measurements at a 10-m elevation, was collected from January 2007 to December 2022 (16 years), with a complete record of all data points. The Weibull distribution function, along with its different parameters, was used to characterize wind energy along the Egyptian Mediterranean Coast. The coefficient of determination (R2), root mean squared error (RMSE), and relative root mean squared error (RRMSE) for the Weibull parameters, along with the relative percentage errors (RPE) for the wind power density were calculated to assess the concordance between outcomes derived from observed data and those predicted by the Weibull function.

Results
Results revealed that the dominant wind direction along the Egyptian Mediterranean Coast was the NNW to N wind, except at Ar where the dominant wind was S. The wind velocity range of 4–6 m/s dominated RE, AQ, and PS. At MM and Ar, this was reduced to 2–4 m/s. The analysis of wind power density outlined significant insights into the potential for wind energy generation in the region. The overall analysis showed that AQ and PS were potentially the most suitable locations for wind energy projects. However, the high variability at the AQ site required robust system designs to manage the fluctuating wind conditions. PS might be more suitable for projects prioritizing stability and consistency over maximum energy output. Although Arish, characterized by its lower wind power density, may be less conducive for large-scale wind energy projects, it could still be viable for smaller installations or when integrated with other renewable energy sources.

Conclusions
The different statistical indices reflected good model fitting, displaying the reliability of the Weibull distribution as a tool for preliminary wind resource assessment along the Egyptian Mediterranean Coast and facilitating accurate predictions of wind power availability.
A real-time predicting online tool for detection of people’s emotions from Arabic tweets based on big data platforms
Authors: Abdelhady Naglaa , Elsemman Ibrahim E. , Soliman Taysir Hassan A. 
Published: November 2024

AbstractEmotion prediction is a subset of sentiment analysis that aims to extract emotions from text, speech, or images. The researchers posit that emotions determine human behavior, making the development of a method to recognize emotions automatically crucial for use during global crises, such as the COVID-19 pandemic. In this paper, a real-time system is developed that identifies and predicts emotions conveyed by users in Arabic tweets regarding COVID-19 into standard six emotions based on the big data platform, Apache Spark. The system consists of two main stages: (1) Developing an offline model and (2) Online emotion prediction pipeline. For the first stage, two different approaches: The deep Learning (DL) approach and the Transfer Learning-based (TL) approach to find the optimal classifier for identifying and predicting emotion. For DL, three classifiers are applied: Convolutional Neural Network (CNN), Gated Recurrent Unit (GRU), and Bidirectional GRU (BiGRU). For TL, five models are applied: AraBERT, ArabicBERT, ARBERT, MARBERT, and QARiB. For the second stage, create a Transmission Control Protocol (TCP) socket between Twitter’s API and Spark used to receive streaming tweets and Apache Spark to predict the label of tweets in real-time. The experimental results show that the QARiB model achieved the highest Jaccard accuracy (65.73%), multi-accuracy (78.71%), precision-micro (78.71%), recall-micro (78.71%), f-micro (78.71%), and f-macro (78.55%). The system is available as a web-based application that aims to provide a real-time visualization of people’s emotions during a crisis.
Assessment of mitochondrial function and its prognostic role in sepsis: a literature review
Authors: Nedel Wagner , Strogulski Nathan Ryzewski , Kopczynski Afonso , Portela Luis Valmor 
Published: November 2024

AbstractSepsis is characterized by a dysregulated and excessive systemic inflammatory response to infection, associated with vascular and metabolic abnormalities that ultimately lead to organ dysfunction. In immune cells, both non-oxidative and oxidative metabolic rates are closely linked to inflammatory responses. Mitochondria play a central role in supporting these cellular processes by utilizing metabolic substrates and synthesizing ATP through oxygen consumption. To meet fluctuating cellular demands, mitochondria must exhibit adaptive plasticity underlying bioenergetic capacity, biogenesis, fusion, and fission. Given their role as a hub for various cellular functions, mitochondrial alterations induced by sepsis may hold significant pathophysiological implications and impact on clinical outcomes. In patients, mitochondrial DNA concentration, protein expression levels, and bioenergetic profiles can be accessed via tissue biopsies or isolated peripheral blood cells. Clinically, monocytes and lymphocytes serve as promising matrices for evaluating mitochondrial function. These mononuclear cells are highly oxidative, mitochondria-rich, routinely monitored in blood, easy to collect and process, and show a clinical association with immune status. Hence, mitochondrial assessments in immune cells could serve as biomarkers for clinical recovery, immunometabolic status, and responsiveness to oxygen and vasopressor therapies in sepsis. These characteristics underscore mitochondrial parameters in both tissues and immune cells as practical tools for exploring underlying mechanisms and monitoring septic patients in intensive care settings. In this article, we examine pathophysiological aspects, key methods for measuring mitochondrial function, and prominent studies in this field.
CT radiation dose reduction with tin filter for localisation/characterisation level image quality in PET-CT: a phantom study
Authors: Bebbington Natalie Anne , Østergård Lone Lange , Christensen Kenneth Boye , Holdgaard Paw Christian 
Published: November 2024

Abstract
Background
The tin filter has allowed radiation dose reduction in some standalone diagnostic computed tomography (CT) applications. Yet, ‘low-dose’ CT scans are commonly used in positron emission tomography (PET)-CT for lesion localisation/characterisation (L/C), with higher noise tolerated. Thus, dose reductions permissible with the tin filter at this image quality level may differ. The aim was to determine the level of CT dose reduction permitted with the tin filter in PET-CT, for comparable image quality to the clinical reference standard (CRS) L/C CT images acquired with standard filtration.

Materials and methods
A whole-body CT phantom was scanned with standard filtration in CRS protocols, using 120 kV with 20mAs-ref for bone L/C (used in 18F-Sodium Fluoride (NaF) PET-CT) and 40mAs-ref for soft tissue L/C (used in 18F-Fluorodeoxyglucose (FDG) PET-CT), followed by tin filter scans at 100 kV (Sn100kV) and 140 kV (Sn140kV) with a range of mAs settings. For each scan, effective dose (ED) in an equivalent-sized patient was calculated, and image quality determined in 5 different tissues through quantitative (contrast-to-noise ratio) and qualitative (visual) analyses. The relative dose reductions which could be achieved with the tin filter for comparable image quality to CRS images were calculated.

Results
Quantitative analysis demonstrated dose savings of 50–76% in bone, 27–51% in lung and 8–61% in soft tissue with use of the tin filter at Sn100kV. Qualitative analysis demonstrated dose reductions using Sn100kV in general agreement with the dose reductions indicated by quantitative analysis. Overall, CT dose reductions of around 85% were indicated for NaF bone PET-CT, allowing whole-body CT at just 0.2mSv ED, and a 30–40% CT dose reduction for FDG PET-CT using Sn100kV (1.7-2.0mSv), providing comparable image quality to current CRS images with standard filtration. Sn140kV demonstrated limited value in CT dose reduction.

Conclusions
Large CT dose reductions can be made using the tin filter at Sn100kV, when imaging bone, lung and soft tissue at L/C level CT image quality in PET-CT. As well as reducing the risk of inducing a cancer in later life, such dose reductions may also impact PET-CT practice, such as justifying cross-sectional over planar imaging or justifying PET-CT in younger patients.
The risk of upper gastrointestinal bleeding associated with concomitant proton pump inhibitor administration during dual antiplatelet therapy with aspirin and prasugrel: a retrospective single-center study
Authors: Ide Yutaro , Morikawa Go , Yoshida Kyohei , Takano Yuki , Kubota Ken , Okazawa Katsuko , Yasu Takeo 
Published: November 2024

Abstract
Objective
Dual‐antiplatelet therapy (DAPT) and proton pump inhibitor (PPI) are frequently prescribed after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) placement. However, studies that evaluate the optimal PPI when used as primary prevention in patients without a history of peptic ulcer disease or upper gastrointestinal bleeding (UGIB), particularly in the context of DAPT involving prasugrel, are lacking. This study aimed to assess the efficacy and safety of PPI use in preventing UGIB in this patient population.

Methods
This study included patients who underwent PCI with coronary stent placement for acute coronary syndrome or stable angina at our institution from January 2015 to December 2020. Eligible patients started DAPT with aspirin and prasugrel and concomitantly received PPI therapy (lansoprazole or esomeprazole), with a follow-up period of two years. The primary endpoint was UGIB incidence, diagnosed during follow-up, serving as an efficacy measure. Secondary endpoints included the assessment of major bleeding (as defined by the Thrombolysis in Myocardial Infarction major bleeding criteria) and clinically relevant non-major bleeding events. Safety outcomes focused on adverse event incidence attributable to PPI use.

Results
Among the 165 patients analyzed, 109 and 56 were included in the lansoprazole and esomeprazole groups, respectively, with cumulative incidence of UGIB at 96 weeks of 0.9% (1/109) and 3.6% (2/56). No significant differences in terms of major bleeding events or other bleeding outcomes were observed between the two groups. Adverse events related to PPI use were reported as diarrhea/soft stools in 7 (6%) cases and thrombocytopenia in 1 (1%) case in the lansoprazole group, whereas no such events were observed in the esomeprazole group. No clinically significant hematologic or biochemical abnormalities were reported.

Conclusion
This study evaluated the efficacy and safety of PPIs in combination with DAPT, including prasugrel, following PCI, and suggests that lansoprazole and esomeprazole may offer comparable efficacy in preventing UGIB.
Exploring the role of oxidative stress and mitochondrial dysfunction in β-damascone-induced aneuploidy
Authors: Hashizume Tsuneo , Munakata Satoru , Takahashi Tomohiro , Watanabe Taku 
Published: November 2024

Abstract
Background
The rose ketone β-damascone (β-Dam) elicits positive results in the in vitro micronucleus (MN) assay using human lymphocytes, but shows negative outcomes in the Ames test and combined in vivo MN and comet assays. This has led to the interpretation that the in vitro MN result is a misleading positive result. Oxidative stress has been suggested as an indirect mode of action (MoA) for in vitro MN formation, with the α, β-unsaturated carbonyl moiety of the β-Dam chemical structure expected to cause misleading positive results through this MoA. In this study, we investigated the role of oxidative stress in β-Dam-induced in vitro MN formation by co-treatment with the antioxidant N-acetyl-l-cysteine (NAC), thereby highlighting a possible link between mitochondrial dysfunction and aneugenicity.

Results
β-Dam induced MN formation in both CHL/IU and BEAS-2B cells, with the response completely inhibited by co-treatment with NAC. Moreover, β-Dam induced oxidative stress-related reporter activity in the ToxTracker assay and increased reactive oxygen species levels, while decreasing glutathione levels, in BEAS-2B cells in the high-content analysis. All of these effects were suppressed by NAC co-treatment. These findings indicate that β-Dam elicits oxidative stress, which causes DNA damage and ultimately leads to MN induction. However, no significant DNA damage-related reporter activities were observed in the ToxTracker assay, nor was there an increased number of γH2AX foci in the high-content analysis. These data suggest that MN formation is not a DNA-reactive MoA. Considering recent reports of aneuploidy resulting from chromosome segregation defects caused by mitochondrial dysfunction, we investigated if β-Dam could cause such dysfunction. We observed that the mitochondrial membrane potential was dose-dependently impaired in BEAS-2B cells exposed to β-Dam.

Conclusions
These findings suggest that the oxidative stress induced by β-Dam exposure may be explained through an aneugenic MoA via mitochondrial dysfunction, thereby contributing to MN formation in mammalian cells.
Antiosteoporotic activity of lupeol on postmenopausal symptoms through promoting estrogenic activity and bone markers in ovariectomized rats
Authors: Bhalerao Tanmayee , Mandlik Deepa , Rojatkar Supada , Bodhankar Subhash , Sathiyanarayanan Arulmozhi 
Published: November 2024

Abstract
Background
Menopause is caused by age-related follicular degeneration and is marked by menstrual cycle cessation with insufficiency of an ovarian hormone, particularly estrogen. Estrogen insufficiency causes vasomotor and urogenital symptoms, as well as an increased risk of osteoporosis. Lupeol (LP) is a triterpene compound found in aloe leaves, carrot root, mango pulp, melon seeds, cucumber, soybean, and other plants. The present study aims to assess the effect of LP on estrogen insufficiency in ovariectomy-induced postmenopausal osteoporosis in rats. Female rats were ovariectomized bilaterally and placed into five groups (n = 8) as ovariectomy control (OVX), standard (17β-Estradiol 50 µg/kg) group, and LP (25, 50, and 100 mg/kg) groups. Two additional groups Normal Control (NC) and Sham Control (SC) rats went through a sham operation procedure. The rats were given an oral dose for 90 days. The tail skin temperature (TST) was recorded every day, and vaginal cornification was assessed every fourth day. Serum hormones, biochemical parameters, bone physical, radiographic, and histological markers were measured on the 90th day of treatment.

Results
In LP-treated rats, there was a decrease in TST, induction of vaginal cornification, improved serum hormonal and lipid profile, improved bone physical properties, increased bone density, and enhanced cytological and histological alterations.

Conclusions
These findings imply that LP exhibited an antiosteoporotic activity against postmenopausal symptoms in ovariectomized rats, suggesting that it could be used therapeutically to treat menopausal problems.