bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Risk of Progression from Barrett’s Esophagus to Esophageal Adenocarcinoma with a Mass-Spectrometry-Based Proteomic Panel
Authors: Cannon Andrew , Hiatt Mark , Ban Igor , Sayad Saed , Karkus Ted , Hartley Christopher 
Published: October 2024

AbstractBackgroundEsophageal adenocarcinoma (EAC) is a highly aggressive cancer with poor prognosis, often arising from gastroesophageal reflux disease (GERD) and its precursor, Barrett’s esophagus (BE). Although only a small proportion of individuals with GERD or BE develop EAC, accurately identifying those at high risk is critical for early intervention. Current surveillance methods, such as endoscopy, are invasive and have limited accuracy in predicting malignant transformation. Mass-spectrometry-based proteomics offers a promising alternative by identifying protein biomarkers associated with disease progression.MethodThis study evaluated an eight-protein panel in predicting the risk of progression from BE to BE with high-grade dysplasia or EAC, potentially improving early detection and patient outcomes. A cohort of 107 subjects diagnosed with BE was recruited, and biological samples (tissue biopsies) were collected and labeled by a pathologist. Proteomic analysis was conducted using mass spectrometry to profile protein expression across the samples. A statistical test (t-test) was applied to assess differences in the proteomic panel across BE that progressed on follow-up compared to BE without progression.ResultsThe t-test results revealed significant differences in protein expression levels between subjects with BE who progressed to cancer and those who did not. Key proteins, including CNDP2_TVF, DAD1 (detected via the FLE and ADF peptides), and GPI_LQQ, demonstrated strong statistical significance (p < 0.001) for under-expression, suggesting their potential as early biomarkers for identifying individuals at high risk. S100p_YSG also showed meaningful under-expression (p = 0.0111), indicating its relevance in cancer progression pathways. In contrast, LTF_DGA was over-expressed (p = 0.0226), possibly serving as an activator in the progression pathway and offering a novel therapeutic target.ConclusionsThis study identified promising biomarkers on the panel—including CNDP2_TVF, DAD1 (detected via the FLE and ADF peptides), and GPI_LQQ—associated with the development of advanced cancer in BE. Their under-expression could inform novel diagnostic and therapeutic approaches. Integrating these protein profiles with genetic and epigenetic data may provide a more complete understanding of disease progression. Longitudinal studies tracking protein levels over time may also reveal their potential as early cancer markers.
Clinical Relevance and Applicability of the 2022 World Health Organization Classification of Childhood B Lymphoblastic Leukemia in the Context of MRD-Directed Therapy
Authors: Rajpal Sweta , Chatterjee Gaurav , Bhanshe Prasanna , Terse Vishram , Joshi Swapnali , Chaudhary Shruti , Shetty Dhanalaxmi , Mohanty Purvi , Dhamne Chetan , Tembhare Prashant , Srinivasan Shyam , Chichra Akanksha , Malik Nirmalya Roy , Banavali Shripad , Gujral Sumeet , Narula Gaurav , Subramanian PG , Patkar Nikhil 
Published: October 2024

AbstractWHO5-2022 classification of B-lymphoblastic leukemia (B-ALL) incorporates several novel entities requiring high-throughput sequencing for their accurate characterization. The clinical relevance of this classification in the context of contemporary MRD-directed therapy is unclear. We analyzed 533 pediatric B-ALL uniformly treated with ICiCLe-ALL-14 protocol as defined by WHO2016 and reclassified them as per WHO5-2022 using targeted sequencing, FISH, and cytogenetics. Subtype-defining genetic abnormalities were identified in 81.2% of the cohort as per the WHO5 classification. Among the new subtypes,PAX5alt,MEF2D-r, andBCR::ABL1-like(ABL-class) were associated with an inferior 2-year event-free survival (EFS) of 39.1% (p<0.0001), 53.8% (p=0.024) and 60.6% (p=0.043), respectively. We developed a 3-tier genetic risk stratification model incorporating 15 genetic subtypes and theIKZF1deletion. Children with standard, intermediate, and high genetic risk demonstrated 2-year EFS of 92.6%, 71.0%, and 50.7% (p<0.0001), and 2-year overall survival of 94.3%, 81.9%, and 71.6% (p<0.0001), respectively. Genetic risk further identified heterogeneous outcomes among ICiCLe risk groups (p<0.0001). Standard genetic risk was associated with superior OS and EFS irrespective of MRD status. We demonstrate the applicability of the WHO5 classification in routine practice and create a general framework for incorporating the WHO5 classification in risk-adapted therapy for childhood B-ALL.
Sleep pressure propels cerebrovascular oscillations while sleep intensity correlates with respiration- and cardiac-driven brain pulsations
Authors: Ulv Larsen Sara Marie , Holst Sebastian Camillo , Olsen Anders Stevnhoved , Ozenne Brice , Zilstorff Dorte Bonde , Brendstrup-Brix Kristoffer , Weikop Pia , Pleinert Simone , Kiviniemi Vesa , Jennum Poul Jørgen , Nedergaard Maiken , Knudsen Gitte Moos 
Published: October 2024

AbstractThe waste-clearing flow of cerebrospinal fluid through the brain is driven by cerebrovascular, respiratory, and cardiac forces and is thought to be regulated by homeostatic sleep mechanisms. In a circadian-controlled sleep and sleep deprivation study, we investigated how heightened sleep pressure and slow-wave-rich sleep affect physiological brain oscillations in humans, as measured with accelerated neuroimaging. Our study also included a randomised, double-blind, placebo-controlled, cross-over administration of the adrenergic antagonist carvedilol, which allowed us to examine the effect of modulating cerebrovascular pulsatility. We report that sleep deprivation increases low frequency brain oscillations (LFOs) more than sleep does, with LFOs during sleep correlating with cognitive measures of sleep pressure. Conversely, slow-wave-rich NREM sleep (stages N2 and N3) enhances respiration- and cardiac-driven brain pulsations – particularly within grey and white matter. The strength of these brain pulsations escalates with sleep depth (N3 > N2) and correlates with EEG delta power. Carvedilol dampens LFOs, supporting that these reflect cerebrovascular oscillations. Altogether, our findings indicate that sleep pressure promotes cerebrovascular oscillations, while sleep slow waves synchronise with respiration- and cardiac-driven brain pulsations.Graphical Abstract
Factors to Perceived Quality of Community Based Health Insurance Utilization Among Admitted Patients at St. Paul’s Hospital Millennium Medical College and AaBET Hospital, Addis Ababa, Ethiopia
Authors: Guddu Dessalegn Keney , Asres Yared Lasebew , Dullo Abrham Getachew , Shawel Tefaye Getachew 
Published: October 2024

AbstractBackgroundCommunity based health insurance(CBHI) was introduced by the Ethiopian government in 2011 with the aim to improve access and quality of health care to the poor informal workers. But studies show that CBHI scheme based service quality is also reported to be low.On the other hand, there has been scarcity of data on barriers to quality of service utilized particularly at hospital level by the insured patients.ObjectiveThe aim of this study was to identify the barriers to good quality of community based health insurance utilization among admitted patients at St. Paul’s Hospital Millenium Medical College and AaBET Hospital, Ethiopia.MethodsCross sectional mixed design implementing quantitative from chart review as well as qualitative study using phenomenological design using focused group discussion and indepth interview involving the concerned CBHI stake holders was conducted from June1-July15,2023. Opendata kit (ODK) was used for quantitatie data collection and SPSS V25 and NVIVO V12 were used for data analysis.ResultsTotal of 396 clients participated in the study. The mean age of study particiapnts was 43.64± 14.3 years. over all, 72.7% of admitted patients have got good quality community-based health insurance services.Factors significantly affecting quality of CBHI utilization were a clean and attractive hospital environment [AOR = 2.77:95% CI (1.24–6.165)], satisfied with community based health insurance [AOR = 2.45:95% CI (1.11–5.39)] at enrollment, good knowledge of the CBHI scheme [AOR = 1.97:95% CI (1.2– 3.23)], adequate availability of information on CBHI services in hospital [AOR = 2.37:95% CI (1.34–4.21)], higher family monthly income between 5251 and 7800 [AOR = 1.97:95% CI (1.2–3.23)], income more than 7801 birr [AOR = 5.3:95% CI (2.32–10.23)] respectively. The barriers to good quality utilization identified with qualitative exploration include difficulty in accessing hospital service areas(inconvenient) and information, limitation on the type of service provided by the scheme, poor knowledge of patients, overcrowding, long waiting times for chart activation, shortage of drugs and inpatient bedsConclusion and recommendationThis study determined that the magnitude of good quality community-based health insurance services utilization was moderate compared to previous studies.Policymakers and stakeholders should improve monitoring of quality of CBHI services and further multicenter studies are necessary to improve service quality in public hospitals of Addis Ababa.
Parallel Analysis of Pharmaceuticals and Viruses in Wastewater: An Untargeted Approach to Tracking Population-Level Respiratory Illness Burden
Authors: Baumgartner Stephan , Salvisberg Michelle , Schmidhalter Patrick , Julian Timothy R , Ort Christoph , Singer Heinz 
Published: October 2024

1AbstractWastewater-based surveillance is widely used for the detection and tracking of priority respiratory pathogens. In this study, pharmaceuticals are tracked in wastewater as an untargeted indicator of symptoms related to acute respiratory infections and influenza-like illnesses, such as coughing, fever, and pain, coincident to respiratory viral loads.From January 2021 to June 2024, wastewater samples from ten wastewater treatment plants across Switzerland serving 23% of the population were analyzed. The analysis encompassed 15 pharmaceuticals and priority respiratory viruses SARS-CoV-2, respiratory syncytial virus, influenza A, and influenza B. Pharmaceutical data were further benchmarked against national clinical surveillance data on a broader range of respiratory pathogens.The pharmaceutical compounds dextrorphan (indicative of dextromethorphan), pheniramine, clarithromycin, acetaminophen, and codeine showed a strong correlation with respiratory viral loads. This enabled the estimation of pathogen-specific and cumulative symptom burdens in the population. Additionally, notable increases in pharmaceutical loads without corresponding increases in viral loads in 2021 and 2024 signaled high community symptom burdens linked to unsurveilled pathogens.The study demonstrates that pharmaceutical surveillance can inform respiratory disease burden and highlights the broader potential of integrated surveillance to assess population-scale symptoms, indicating emerging public health threats beyond those routinely monitored.
Academic stress through salivary biomarkers: A multivariate analysis of cortisol, IL-1β, CRP, and IgA levels and their variations as a function of sex
Authors: Klagges Rodrigo Castillo , Sáez Camila Pezo , Aguila Luis , Pantoja Verónica , Seguel Favián Treulen 
Published: October 2024

AbstractIntroductionAcademic stress can activate physiological changes mediated by the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis, triggering the release of biomarkers such as cortisol and proinflammatory cytokines. Although physiological stress has been studied in relation to different inducers and diseases, there is still a gap regarding the association of academic stress with biological markers. Thus, this study aimed to associate the levels of academic stress against biological markers isolated from saliva from undergraduates’ students.Materials and methods81 students (53 women and 28 men) were recruited and completed the SISCO inventory to determine the level of academic stress. The levels of cortisol, interleukin-1β (IL-1β), C-reactive protein (CRP) and immunoglobulin A (IgA) from saliva samples were determined by ELISA assays, and data were analyzed using ANOVA, Pearson correlation tests. A predictor model was estimated by lineal regression.ResultsStress categorization following the SISCO inventory showed that 37% of the students grouped in the low stress level (<48%), 35% grouped in the moderate stress level (>49% <60%), and 28% in high stress level (>61% <100%). The levels of salivary markers were similar across stress categories, however the trends identified—such as the decrease in cortisol and the increase in pro-inflammatory markers in male participants categorized in the high stress group—suggest a possible association between these biomarkers with academic stress gender-dependent. The multivariable model including the 4 biomarkers resulted in R2= 0.14 with predictions that were roughly within +/-20% of stress levels.ConclusionIn conclusion, no significance was found in the association of salivary biomarkers with academic stress levels. However, trends were observed with increasing levels of academic stress in men. The concentration of these biomarkers may be affected by sex. Further research will consider individual factors, longitudinal assessments, and the use of multiple psychometric tools to better define the interaction between academic stress and salivary biomarkers.
Chronic recording of brain activity in awake toads
Authors: Shaykevich Daniel A. , Woods Grace A. , O’Connell Lauren A. , Hong Guosong 
Published: October 2024

ABSTRACTBackgroundAmphibians represent an important evolutionary transition from aquatic to terrestrial environments and they display a large variety of complex behaviors despite a relatively simple brain. However, their brain activity is not as well characterized as that of many other vertebrates, partially due to physiological traits that have made electrophysiology recordings difficult to perform in awake and moving animals.New methodWe implanted flexible mesh electronics in the cane toad (Rhinella marina) and performed extracellular recordings in the telencephalon of anesthetized toads and partially restrained, awake toads over multiple days.ResultsWe recorded brain activity over five consecutive days in awake toads and over a 15 week period in a toad that was anesthetized during recordings. We were able to perform spike sorting and identified single- and multi-unit activity in all toads.Comparison with existing methodsTo our knowledge, this is the first report of a modern method to perform electrophysiology in non-paralyzed toads over multiple days, though there are historical references to short term recordings in the past.ConclusionsImplementing flexible mesh electronics in amphibian species will allow for advanced studies of the neural basis of amphibian behaviors.
Methylation Clocks Do Not Predict Age or Alzheimer’s Disease Risk Across Genetically Admixed Individuals
Authors: Cruz-González Sebastián , Gu Esther , Gomez Lissette , Mews Makaela , Vance Jeffery M. , Cuccaro Michael L. , Cornejo-Olivas Mario R. , Feliciano-Astacio Briseida E. , Byrd Goldie S. , Haines Jonathan L. , Pericak-Vance Margaret A. , Griswold Anthony J. , Bush William S. , Capra John A. 
Published: October 2024

AbstractEpigenetic clocks that quantify rates of aging from DNA methylation patterns across the genome have emerged as a potential biomarker for risk of age-related diseases, like Alzheimer’s disease (AD), and environmental and social stressors. However, methylation clocks have not been validated in genetically diverse cohorts. Here we evaluate a set of methylation clocks in 621 AD patients and matched controls from African American, Hispanic, and white co-horts. The clocks are less accurate at predicting age in genetically admixed individuals, especially those with substantial African ancestry, than in the white cohort. The clocks also do not consistently identify age acceleration in admixed AD cases compared to controls. Methylation QTL (meQTL) commonly influence CpGs in clocks, and these meQTL have significantly higher frequencies in African genetic ancestries. Our results demonstrate that methylation clocks often fail to predict age and AD risk beyond their training populations and suggest avenues for improving their portability.
Unlocking the role of SH3PXD2B in epithelial-to-mesenchymal transition driving Breast Cancer Lung Metastasis
Authors: Das Subhajit , Khilwani Riya , Singh Shailza 
Published: October 2024

AbstractDespite advancements in breast cancer treatment, metastasis remains a significant challenge, contributing to high mortality rates. This study investigates the mechanisms underlying breast cancer lung metastasis, with a particular emphasis on the role of SH3PXD2B in driving epithelial-to-mesenchymal transition. Here, we analyzed RNA sequencing data from CCLE and TCGA databases and characterized that SH3PXD2B expression is elevated in breast cancer (BC) and lung cancer (LC) tissues compared to non-transformed tissues. Bioinformatics analysis revealed that SH3PXD2B regulates several cellular processes and is associated with poor prognosis in breast cancer (BRCA) and lung adenocarcinoma (LUAD) patients. Functional experiments underscore that the upregulation of SH3PXD2B promoted BC and LC cell migration in vitro; however, its knockdown inhibited the effect. Mechanistically, the mass spectrometry analysis was utilized to pull down interacting partners of SH3PXD2B, and the findings were substantiated by immunoblotting. Additionally, our findings on immunofluorescence and gene expression analysis demonstrated the additive role of SH3PXD2B and migratory proteins in promoting breast cancer progression. Further, we performed bioluminescent IVIS imaging analysis to trace the metastatic spread of MDA-MB-468 cells and observed strong signals and a high degree of dissemination to distant organs. Collectively, our results highlight the importance of SH3 domains in aggravating breast transformation, which can therefore serve as a promising therapeutic strategy in counteracting breast-related malignancy.Abstract Figure
Evolution of Key Factors Influencing Performance Across Phases in Junior Short Sprints
Authors: Oku Kyosuke , Kai Yoshihiro , Koda Hitoshi , Gonno Megumi , Tanaka Maki , Matsui Tomoyuki , Watanabe Yuya , Morihara Toru , Kida Noriyuki 
Published: October 2024

AbstractSprint performance plays a crucial role in various sports. Short sprints vary in court size and competitive characteristics but are common in many sports. Although the relationship between age and muscle strength has been explored in short sprints, there is limited understanding of how various physical factors interact, particularly concerning differences in the acceleration phase. This study examined the relationship between sprint times at 0‒2.5 m, 2.5‒5 m, and 5‒10 m intervals and various factors in junior athletes. Results indicated that sprint times increased with age, and is correlated with muscle strength and flexibility. Partial correlation analysis showed that faster times in the 0‒2.5 m interval were associated with higher hip flexibility; in the 2.5‒5 m interval, faster times were associated with higher core flexibility; and in the 5‒10 m interval, a relationship with standing long jump performance was confirmed. Furthermore, lower fat-free body weight translated to higher performance. In the acceleration phase of 10 m, flexibility immediately after the start and the subsequent horizontal propulsive force is important factors that are strongly related to performance change in each interval. The study results illuminate the mechanism behind short sprints in junior athletes and emphasize the importance of daily training, considering the sprint distance required for each sport.
Discovery and Biosynthesis of Sulfenicin and Its New-to-Nature Acylsulfenic Acid Functional Group
Authors: Xue Dan , Zou Hongbin , Lv Wei , Madden Michael D. , Lian Xiaoying , Xu Mingming , Pulliam Conor , Older Ethan A. , Hou Lukuan , Campbell Andrew , de Rond Tristan , Awakawa Takayoshi , Yuan Chunhua , Moore Bradley S. , Li Jie 
Published: October 2024

AbstractLife’s organic molecules are built with diverse functional groups that enable biology by fine tuning intimate connections through time and space. As such, the discovery of new-to-nature functional groups can expand our understanding of the natural world and motivate new applications in biotechnology and biomedicine. Herein we report the genome-aided discovery of sulfenicin, a novel polyketide-nonribosomal peptide hybrid natural product from a marineStreptomycesbacterium bearing a unique acylsulfenic acid functionality. Through a series of heterologous biosynthesis, functional genetics, and enzymatic reconstitution experiments, we show that this previously described synthetic functional group is biologically assembled by a set of enzymes from both primary and secondary metabolism, including a novel flavin-dependentS-hydroxylase that hydroxylates a thiocarboxylic acid’s sulfur atom. While the sulfenicin biosynthetic gene cluster is presently without parallel in public databases, acylsulfenic acid-encoding enzymes are widely distributed in bacterial genomes, implying that this labile functional group may similarly have a broad distribution among specialized metabolites.
Exogenous selenium supplements reduce cadmium accumulation and restores micronutrient content in rice grains
Authors: Barman Falguni , Guha Titir , Kundu Rita 
Published: October 2024

AbstractPurposeCadmium (Cd) contamination in agricultural soil and accumulation in rice poses serious threat to human health. It is reported that Selenium (Se) can mitigate the toxic effect of Cd in rice. But the underlying mechanism of Se preventing the Cd accumulation and restoring the micronutrient content in rice grains have not been studied before. Therefore, our main aim is to reduce Cd content and restore micronutrient content in rice grain and study the mechanism.MethodsTwo indigenous rice genotypes (Maharaj and Jamini) were exposed to 10 and 50 µM Cd in presence and absence of Se (5µM) with a control set and assessed for plant growth, biomass, Cd content, ROS and antioxidants for Cd induced toxicity and amelioration. Genes for micronutrient transporters were studied by RT-PCR. Grain Cd and micronutrient content and agronomic parameters were also studied.ResultsSe supplementation increased plant growth, biomass, and yield under Cd stress. SEM and EDX analysis revealed that Se-Cd complex formed on root surfaces restricted Cd uptake by the roots preventing root damage. Soil analysis confirmed that Se decreased Cd bioavailability, restricted root to shoot Cd translocation, ultimately reducing Cd accumulation and restoring micronutrients in grain. This was further validated by fluorescent Leadmium dye staining. In (Se+Cd) treated seedlings, up-regulation of S metabolism and nutrient transporter genes also contributed to the mitigation of Cd stress.ConclusionsSo, the Se supplementation can be considered as a cost-effective, ecofriendly and sustainable approach to produce Cd free rice cultivation in Cd polluted soil.