bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biovalorization of whey waste as economic nutriment for mycogenic production of single cell oils with promising antibiofilm and anticancer potentiality
Authors: Eltarahony Marwa , El-deeb Nehal , Abu‑Serie Marwa , El‑Shall Hadeel 
Published: November 2024

AbstractThe production of value-added bio-compounds from rejuvenated sources and their recruitment for healthcare services are paramount objectives in the agenda of white biotechnology. Hereupon, the current study focused on economic production of single cell oils (SCOs) from oleaginous fungi Alternaria sp. (A-OS) and Drechslera sp. (D-OS) using cheese whey waste stream, followed by their evaluation as antibiofilm and anticancer agents, for the first time. As a sole substrate for growth, the whey aided in lipid accumulation by 3.22 and 4.33 g/L, which representing 45.3 and 48.2% lipid content in Drechslera sp. (D-OS) and Alternaria sp. (A-OS), respectively. Meanwhile, a higher unsaturation degree was detected in A-OS by 62.18% comparing to 53.15% of D-OS, with advantageous presence of omega-6 poly unsaturated fatty acid by 22.67% and 15.04% for A-OS and D-OD, respectively, as revealed by GC-MS and FTIR characterization analysis. Interestingly, an eminent and significant (P ≤ 0.05) antibiofilm potency was observed in a dose-dependent modality upon employing both SCOs as antibiofilm agents. Whereas, 100 µg/mL of A-OS recorded superior inhibition of P. aeruginosa, S. aureus and C. albicans biofilms development by 84.10 ± 0.445, 90.37 ± 0.065 and 94.96 ± 0.21%, respectively. Whereas, D-OS (100 µg/mL) thwarted the biofilms of P. aeruginosa, S. aureus and C. albicans by 47.41 ± 2.83, 62.63 ± 5.82 and 78.67 ± 0.23%, correspondingly. Besides, the metabolic performance of cells within biofilm matrix, protein, carbohydrate contents and hydrophobicity of examined biofilms were also curtailed in a significant correlation with biofilm biomass (r ≥ 0.9). Further, as anticancer agents, D-OS recorded higher potency against A549 and CaCo-2 cell lines with IC50 values of 2.55 and 3.425% and SI values of 10.1 and 7.5, respectively. However, A-OS recorded 8.275% and 2.88 for IC50 and SI of Caco-2 cells, respectively. Additionally, A-OS activated caspase 3 by 64.23 ± 1.18% and 53.77 ± 0.995% more than D-OS (52.09 ± 0.222% and 49.72 ± 0.952%) in A549 and Caco-2 cells, respectively. Furthermore, the enzymes, which associated with cancer invasion, metastasis, and angiogenesis (i.e., MMP2 and MMP9) were strongly inhibited by A-OS with 18.58% and 8.295%, respectively as IC50 values; while D-OS results recorded 23.61% and 13.16%, respectively, which could be ascribed to the higher ω-6/ω-3 contents of A-OS. The promising results of the current study opens up the vision to employ SCOs as anti-infective nutraceuticals and in complementary/alternative therapy and prophylactic programs as well.
Adverse food reactions and alterations in nutritional status in children with autism spectrum disorders: results of the NAFRA project
Authors: Coppola Serena , Nocerino Rita , Oglio Franca , Golia Paola , Falco Maria Candida , Riccio Maria Pia , Carucci Laura , Rea Teresa , Simeone Silvio , Garotti Raffaele , Marani Nadia , Bravaccio Carmela , Canani Roberto Berni 
Published: November 2024

Abstract
Background
To assess the adverse food reactions (AFR) prevalence in children with autism spectrum disorder (ASD) and in non-ASD healthy controls (NASD). Nutritional status alterations, food selectivity and adherence to Mediterranean Diet (MD) were also evaluated.

Methods
The NAFRA (Nutritional status and Adverse Food Reactions in children with Autism Spectrum Disorder) project was an observational, case-control, comparative study conducted at a tertriary center for pediatrics involving Caucasian patients of both sexes, aged 18 months-7 years, with a diagnosis of ASD, and matched NASD controls.

Results
From October 2017 to December 2023, 100 ASD patients [79 male, mean (± SD) age 49.9 months (± 15.4)] and 100 NASD controls [75 male, mean (± SD) age 49.8 months (± 17.7)] were enrolled at the Pediatric Section of the Department of Translational Medical Science of the University of Naples Federico II. A significantly higher prevalence of AFR was observed in ASD patients if compared with NASD (16% vs. 2%, p = 0.001), mainly due to a higher prevalence of food allergy (7% vs. 1%, p = 0.03). A significantly higher prevalence of food intolerance and celiac disease was also observed in ASD children. The rate of obesity was significantly higher in ASD patients compared to NASD. Food selectivity and low MD-adherence were more frequent in ASD children (26% vs. 2%, p < 0.0001 and 28% vs. 16%, p = 0.041, respectively).

Conclusions
The high rate of AFR, obesity and unhealthy dietary habits observed in ASD children strongly suggest the importance of a multidisciplinary approach, providing early diagnosis of AFR and appropriate nutritional management to improve core and associated ASD-related conditions.

Trial registration
The NAFRA Project was registered on https://clinicaltrials.gov/ with the identifier NCT04719923. Registered 18 January 2021. https://clinicaltrials.gov/study/NCT04719923.
Breast cancer in women with previous gestational diabetes: a nationwide register-based cohort study
Authors: Christensen Maria Hornstrup , Vinter Christina Anne , Olesen Thomas Bastholm , Petersen Maria Houborg , Nohr Ellen Aagaard , Rubin Katrine Hass , Andersen Marianne Skovsager , Jensen Dorte Moeller 
Published: November 2024

Abstract
Background
Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk.

Methods
We conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test.

Results
Of 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83–1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk.

Conclusions
This large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.
Differential sensitivity and specificity of Aedes aegypti and Anopheles gambiae to adenine nucleotide phagostimulants—an all-or-none response?
Authors: Lukenge Matthew , Ignell Rickard , Hill Sharon Rose 
Published: November 2024

Abstract
Background
The decision to imbibe a blood meal is predominantly dependent on the sensitivity and specificity of haematophagous arthropods to blood-derived adenine nucleotides, in particular adenosine triphosphate (ATP). Despite previous efforts to identify and characterise the specificity and sensitivity to ATP and other adenine nucleotides, as well as the role of other blood-derived phagostimulants across the Culicidae, comparisons across species remain difficult.

Methods
The feeding response of the yellow fever mosquito Aedes aegypti and the African malaria vector Anopheles gambiae to adenine nucleotides in the presence of a carbonate buffer was assessed using a membrane feeding assay. The proportion of mosquitoes engorged and the volume imbibed by all mosquitoes was scored visually and spectrophotometrically. In addition, the proportion of prediuresing An. gambiae, as well as the volume engorged and prediuresed, was examined.

Results
Aedes aegypti was more sensitive to adenine nucleotides than An. gambiae, but both species maintained specificity to these phagostimulants, demonstrating a dose-dependent bimodal feeding pattern, thereby expanding our understanding of the all-or-none blood-feeding hypothesis. Feeding on the bicarbonate buffer by An. gambiae—but not that of Ae. aegypti—demonstrated a species-specific variation in how blood phagostimulants are encoded. Adenine nucleotides, with and without bovine serum albumin, were observed to dose-dependently regulate the proportion of An. gambiae prediuresing and the volumes prediuresed but not volumes engorged.

Conclusions
Taken together, the results of this study expand our understanding of how mosquitoes differentially assess and respond to blood meal constituents, and provide a basis for further physiological and molecular studies.

Graphical Abstract
Kidnapping-Induced Trauma and secondary stress in armed conflicts: a comparative study among women in hostage families, volunteers, and the General Population
Authors: Livne Shahar , Feldblum Ilana , Kivity Sara , Shamir-Stein Naama , Brand Einat , Cohen Shir , Rotman Eran , Levine Hagai , Saban Mor 
Published: November 2024

Abstract
Background
Exposure to armed conflict negatively impacts health. However, there is limited data on secondary stress from ambiguous loss contexts, such as kidnapping. In this study we aimed to quantify changes in modifiable health behaviors and well-being among women in hostage families and hostage crisis volunteers versus the general female population within the first two months of the 2023 Israel-Hamas war.

Methods
A cross-sectional online survey was conducted on 318 Hebrew-speaking women aged 18–75 in Israel comparing: (1) a general population sample (n = 245); (2) hostage crisis volunteers (n = 40); and (3) hostage family members (n = 33). Participants provided demographic information, details on chronic illnesses, and responded to Likert-scale questions covering self-rated health, mental health, and lifestyle habits before the conflict and in current state.

Results
Hostage family members reported the most severe health impacts, followed by volunteers. Fair/poor physical health status increased significantly in all groups during the war, with hostages’ families reporting the highest rate (61.6%). Mental health deterioration was more pronounced among hostages’ families, with 84% expressing a need for mental health support. Hostages’ families also reported the highest rates of sleep problems, reduced adherence to a healthy lifestyle, and weight loss. Mental and physical health declined significantly across the exposed groups, as measured by multiple assessments, with hostage families experienced the most pronounced impairments across various domains of well-being.

Conclusions
This period of conflict severely harmed the well-being of all women in the study population. Women from all three groups - hostage families, volunteers, and those from the general population - experienced health deterioration due to varying levels of stress and exposure to conflict-related factors. Hostage families faced the greatest impact with nearly all members of this group showing significant health damage. Long-term support is needed to help restore post-conflict health for all affected women. Further research may be needed to determine the most effective interventions for addressing these impacts across the different groups.
Critical role of ROCK1 in AD pathogenesis via controlling lysosomal biogenesis and acidification
Authors: Song Chenghuan , Huang Wanying , Zhang Pingao , Shi Jiyun , Yu Ting , Wang Jing , Hu Yongbo , Zhao Lanxue , Zhang Rui , Wang Gang , Zhang Yongfang , Chen Hongzhuan , Wang Hao 
Published: November 2024

Abstract
Background
Lysosomal homeostasis and functions are essential for the survival of neural cells. Impaired lysosomal biogenesis and acidification in Alzheimer’s disease (AD) pathogenesis leads to proteolytic dysfunction and neurodegeneration. However, the key regulatory factors and mechanisms of lysosomal homeostasis in AD remain poorly understood.

Methods
ROCK1 expression and its co-localization with LAMP1 and SQSTM1/p62 were detected in post-mortem brains of healthy controls and AD patients. Lysosome-related fluorescence probe staining, transmission electron microscopy and immunoblotting were performed to evaluate the role of ROCK1 in lysosomal biogenesis and acidification in various neural cell types. The interaction between ROCK1 and TFEB was confirmed by surface plasmon resonance and in situ proximity ligation assay (PLA). Moreover, we performed AAV-mediated ROCK1 downregulation followed by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and behavioral tests to unveil the effects of the ROCK1–TFEB axis on lysosomes in APP/PS1 transgenic mice.

Results
ROCK1 level was significantly increased in the brains of AD individuals, and was positively correlated with lysosomal markers and Aβ. Lysosomal proteolysis was largely impaired by the high abundance of ROCK1, while ROCK1 knockdown mitigated the lysosomal dysfunction in neurons and microglia. Moreover, we verified ROCK1 as a previously unknown upstream kinase of TFEB independent of m-TOR or GSK-3β. ROCK1 elevation resulted in abundant extracellular Aβ deposition which in turn bound to Aβ receptors and activated RhoA/ROCK1, thus forming a vicious circle of AD pathogenesis. Genetically downregulating ROCK1 lowered its interference with TFEB, promoted TFEB nuclear distribution, lysosomal biogenesis and lysosome-mediated Aβ clearance, and eventually prevented pathological traits and cognitive deficits in APP/PS1 mice.

Conclusion
In summary, our results provide a mechanistic insight into the critical role of ROCK1 in lysosomal regulation and Aβ clearance in AD by acting as a novel upstream serine kinase of TFEB.
Drosophila Toxicogenomics: genetic variation and sexual dimorphism in susceptibility to 4-Methylimidazole
Authors: Collins Katelynne M. , Howansky Elisabeth , Macon-Foley Sarah C. , Adonay Maria E. , Shankar Vijay , Lyman Richard F. , Nazario-Yepiz Nestor Octavio , Brooks Jordyn K. , Lyman Rachel A. , Mackay Trudy F. C. , Anholt Robert R. H. 
Published: November 2024

Abstract
Background
4-methylimidazole is a ubiquitous and potentially carcinogenic environmental toxicant. Genetic factors that contribute to variation in susceptibility to its toxic effects are challenging to assess in human populations. We used the Drosophila melanogaster Genetic Reference Panel (DGRP), a living library of natural genetic variation, to identify genes with human orthologs associated with variation in susceptibility to 4-methylimidazole.

Results
We screened 204 DGRP lines for survival following 24-hour exposure to 4-methylimidazole. We found extensive genetic variation for survival, with a broad sense heritability of 0.82; as well as genetic variation in sexual dimorphism, with a cross-sex genetic correlation of 0.59. Genome-wide association analyses identified a total of 241 candidate molecular polymorphisms in or near 273 unique genes associated with survival. These polymorphisms had either sex-specific or sex-antagonistic effects, and most had putative regulatory effects. We generated interaction networks using these candidate genes as inputs and computationally recruited genes with known physical or genetic interactions. The network genes were significantly over-represented for gene ontology terms involving all aspects of development (including nervous system development) and cellular and organismal functions as well as canonical signaling pathways, and most had human orthologs.

Conclusions
The genetic basis of variation in sensitivity to acute exposure to 4-methylimidazole in Drosophila is attributable to variation in genes and networks of genes known for their effects on multiple developmental and cellular processes, including possible neurotoxicity. Given evolutionary conservation of the underlying genes and pathways, these insights may be applicable to humans.
Intolerance of uncertainty and repetitive negative thinking: transdiagnostic moderators of perfectionism in eating disorders
Authors: Hyde-Smith Craig , Carey Holly , Steward Trevor 
Published: November 2024

AbstractPerfectionism has been identified as a vulnerability and maintenance factor across eating disorders (EDs). Additionally, research has found that intolerance of uncertainty (IU) and repetitive negative thinking (RNT) moderate the relationship between perfectionism and psychopathology. Despite this evidence, few studies have examined if these factors specifically moderate ED severity. This study aimed to fill this gap by investigating the moderating effect of IU and RNT on the relationship between perfectionism and ED symptoms, as well as the predictive power of these factors on identifying participants with clinically significant ED symptoms. 331 treatment-seeking adults from a university-affiliated community clinic and 264 undergraduate students completed measures to assess ED symptoms, RNT, perfectionism and IU. 147 participants (24.7% of the total sample) had clinically significant levels of ED symptoms as determined by the Eating Disorder Questionnaire Short-Form (EDE-QS). Multiple linear regressions found significant associations between ED symptoms and both the IU*perfectionism interaction (p < .001) and the RNT*perfectionism interaction (p < .001). A binary logistic regression identified that both the IU*perfectionism interaction (p = .03) and the RNT*perfectionism interaction (p = .001) predicted clinically significant EDE-QS scores. The findings indicate that both IU and RNT moderate the relationship between perfectionism and ED symptoms and build on previous literature recognising transdiagnostic contributors to ED symptomatology.
Correlation of non-alcoholic fatty liver disease and neurodegenerative disorders
Authors: Jadhav Pranali A. , Thomas Asha B. , Chopada Vinay M. , Bokaria Prajay V. , Deokate Shivam B. , Chougule Pankaj S. , Chavan Pruthviraj N. , Chitlange Sohan S. 
Published: November 2024

AbstractNon-alcoholic fatty liver disease and neurodegenerative disorders represent significant health challenges worldwide, with shared pathophysiological mechanisms. Evolving data indicates a bidirectional relationship between NAFLD and neurodegenerative disorders, with common risk factors, such as metabolic syndrome, inflammation, oxidative stress, and genetic predisposition, contributing to both conditions. Mechanistic links connecting NAFLD and neurodegeneration include systemic inflammation, dysregulation of the gut-liver-brain axis, and vascular dysfunction. This comprehensive review explores the intricate relationship between NAFLD and neurodegenerative disorders, focusing on shared pathophysiological mechanisms, common risk factors, and emerging therapeutic strategies. Furthermore, it presents evidence of the association between NAFLD and neurodegenerative disorders from clinical studies, underscoring the importance of understanding and addressing these interconnected conditions. A broad understanding of the complex linking between NAFLD and neurodegenerative disorders is essential for the advancement of future therapeutic strategies that can effectively lessen the load of these devastating conditions. By unveiling the shared pathophysiological mechanisms, common risk factors, and interconnected pathways linking NAFLD and neurodegeneration, researchers can identify novel therapeutic targets and interventions aimed at halting disease progression and preserving patient health.
Discovery of optimal cell type classification marker genes from single cell RNA sequencing data
Authors: Liu Angela , Peng Beverly , Pankajam Ajith V. , Duong Thu Elizabeth , Pryhuber Gloria , Scheuermann Richard H. , Zhang Yun 
Published: November 2024

Abstract
Background
The use of single cell/nucleus RNA sequencing (scRNA-seq) technologies that quantitively describe cell transcriptional phenotypes is revolutionizing our understanding of cell biology, leading to new insights in cell type identification, disease mechanisms, and drug development. The tremendous growth in scRNA-seq data has posed new challenges in efficiently characterizing data-driven cell types and identifying quantifiable marker genes for cell type classification. The use of machine learning and explainable artificial intelligence has emerged as an effective approach to study large-scale scRNA-seq data.

Methods
NS-Forest is a random forest machine learning-based algorithm that aims to provide a scalable data-driven solution to identify minimum combinations of necessary and sufficient marker genes that capture cell type identity with maximum classification accuracy. Here, we describe the latest version, NS-Forest version 4.0 and its companion Python package (https://github.com/JCVenterInstitute/NSForest), with several enhancements to select marker gene combinations that exhibit highly selective expression patterns among closely related cell types and more efficiently perform marker gene selection for large-scale scRNA-seq data atlases with millions of cells.

Results
By modularizing the final decision tree step, NS-Forest v4.0 can be used to compare the performance of user-defined marker genes with the NS-Forest computationally-derived marker genes based on the decision tree classifiers. To quantify how well the identified markers exhibit the desired pattern of being exclusively expressed at high levels within their target cell types, we introduce the On-Target Fraction metric that ranges from 0 to 1, with a metric of 1 assigned to markers that are only expressed within their target cell types and not in cells of any other cell types. NS-Forest v4.0 outperforms previous versions in simulation studies and on its ability to identify markers with higher On-Target Fraction values for closely related cell types in real data, and outperforms other marker gene selection approaches for cell type classification with significantly higher F-beta scores when applied to datasets from three human organs—brain, kidney, and lung.

Discussion
Finally, we discuss potential use cases of the NS-Forest marker genes, including for designing spatial transcriptomics gene panels and semantic representation of cell types in biomedical ontologies, for the broad user community.