bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community assembly modeling of microbial evolution within Barrett’s esophagus and esophageal adenocarcinoma
Authors: Guccione Caitlin , Sfiligoi Igor , Gonzalez Antonio , Shaffer Justin P. , Kazachkova Mariya , Weng Yuhan , McDonald Daniel , Shah Shailja C. , Minot Samuel S. , Paulson Thomas , Grady William M. , Alexandrov Ludmil B. , Knight Rob , Curtius Kit 
Published: January 2025

AbstractMathematical modeling of somatic evolution, a process impacting both host cells and microbial communities in the human body, can capture important dynamics driving carcinogenesis. Here we considered models for esophageal adenocarcinoma (EAC), a cancer that has dramatically increased in incidence over the past few decades in Western populations, with high case fatality rates due to late-stage diagnoses. Despite advancements in genomic analyses of the precursor Barrett’s esophagus (BE), prevention of late-stage EAC remains a significant clinical challenge. Previous microbiome studies in BE and EAC have focused on quantifying static microbial abundance differences rather than evolutionary dynamics. Using whole genome sequencing data from esophageal tissues, we first applied a robust bioinformatics pipeline to extract non-host DNA reads, mapped these putative reads to microbial taxa, and retained those taxa with high genomic coverage. When applying mathematical models of microbial evolution to sequential stages of progression to EAC, we observed evidence of neutral dynamics in community assembly within normal esophageal tissue and BE, but not EAC. In a case-control study of BE patients who progressed to EAC cancer outcomes (CO) versus those who had non-cancer outcomes (NCO) during follow-up (mean=10.5 years), we found thatHelicobacter pylorideviated significantly from the neutral expectation in BE NCO, suggesting that factors related toH. pyloriorH. pyloriinfection itself may influence EAC risk. Additionally, simulations incorporating selection recapitulated non-neutral behaviors observed in the datasets. Formally modeling dynamics during progression holds promise in clinical applications by offering a deeper understanding of microbial involvement in cancer development.
The Translational Landscape of Reactive Astrocytes Reveals the Impact of eIF2B-mediated Dysregulation in VWM Disease
Authors: Mandelboum Shir , Lev-Ari Liat , Atzmon Andrea , Herrero Melisa , Brezner Naama , Benhalevy Daniel , Elroy-Stein Orna 
Published: January 2025

AbstractA devastating genetic recessive neurodegenerative disorder, Vanishing White Matter Disease (VWMD), stems from mutations in eIF2B—a master regulator of mRNA translation initiation and mediator of cellular stress response. While astrocytes, the brain’s essential support cells, are known to be central to VWMD pathology, the molecular mechanisms underlying their dysfunction remain poorly understood. Our study reveals that even a mild mutation in eIF2B5 profoundly disrupts astrocyte mRNA translation regulation upon cytokine-mediated activation, affecting nearly one-third of all expressed genes. Through innovative integration of RNA-seq and Ribo-seq analyses using primary cell cultures of astrocytes isolated from eIF2B5R132H/R132Hmice, we discovered attempts to compensate for impaired protein production by increasing mRNA levels. However, this compensation proves insufficient to maintain critical cellular functions. Our comprehensive analysis uncovered significant disruptions in cellular energy production and protein synthesis machinery. We also predicted previously unknown defects in cholesterol biosynthesis within mutant astrocytes. Moreover, a meta-analysis of translation initiation scores pinpointed, for the first time, a short list of specific ’effector’ gene candidates that may drive disease progression. This powerful combination of transcriptome and translatome illuminates the complex pathophysiology of VWMD and identifies promising new biomarkers and therapeutic target opportunities.
Receipt of BNT162b2 KP.2 Vaccine and COVID-19 CVS MinuteClinic Visits in US Adults
Authors: Rudolph Abby E. , Khan Farid L. , Sun Xiaowu , Lupton Laura L. , Puzniak Laura A. , Jodar Luis , McLaughlin John M. 
Published: January 2025

AbstractUsing a test-negative design, we modeled the association between receipt of BNT162b2 KP.2 vaccine and symptomatic COVID-19 among adults testing for SARS-CoV-2 at walk-in clinics in a large US retail pharmacy chain (9/5/2024–12/8/2024). At a median of 37 days post-vaccination, those who received BNT162b2 KP.2 were 48% less likely to test positive.
Pan-Cancer Proteogenomic Network Analysis Uncovers Immune Microenvironment and Prognostic Biomarkers
Authors: Shi Wenhan , Guan Runing , Li Jiafeng , Chen Dongjing 
Published: January 2025

AbstractPan-cancer analysis provides valuable insights into common and distinct molecular mechanisms across various cancer types. Co-expression networks, which captured the cordinated expression of genes and proteins, offer potentials for identifying robust biomarkers and targeted therapies. However, current-existing co-expression construction method involves either RNA or Protein data in isolation, limiting our understanding on multi-perspective interactions in cancer. To address this gap, we integerated both the RNA and Protein data to constrcut a comprehensive pan-cancer co-expression network, combining both gene and proteomic layers of information across cancer types. This approach enables the identification of previously undetected co-expression relationships, highlighting key regulatory patterns in cancer analysis. Our study constructed a multi-perspective co-expression network, after that, we identified several conservation modules and compare the modules identified from RNA and Protein. We found out that the conservation modules identified differ significantly from RNA and Protein data. However, there are certain shared conservation modules, especially those related to IFN-gamma, IFN-alpha, and the activation of JAK_STAT. Then we identified several important immune-related pathways using RNA and Protein data and uncovered some modules with high prognostic value across cancers. As a novel pan-cancer analysis approach, it holds promise for advancing future cancer research, from the discovery of novel biomarkers to the design of personalized cancer therapies, thereby enabling more thorough and holistic cancer analysis.
Cytosolic transport of citrate protects nutrient-austere pancreatic cancer from ferroptosis
Authors: Kneebone Adam , Lindaur Kailey , Abbas Ata , Cassel Joel , Graff Sarah , Abood Gerard , Ding Xianzhong , Small William , Tatsuoka Curtis , Sidoli Simone , Salvino Joseph M. , Vaziri-Gohar Ali 
Published: January 2025

AbstractPancreatic cancer (PDAC) cells experience nutrient starvation in a poorly perfused tumor microenvironment. Metabolic dependencies that protect PDAC cells from detrimental oxidative stress in a nutrient-restricted niche represent as tumor-specific targets. While the role of mitochondria in supporting energy production and biosynthetic requirements of cells has been well investigated, their contribution to maintaining intracellular redox homeostasis when PDAC cells are exposed to nutrient deprivation is unknown. Our results demonstrate that cytosolic transport of citrate via SLC25A1 confers a survival advantage to PDAC cells by protecting them from ferroptosis, a well-established iron-dependent cell death mechanism, under nutrient-limited conditions. Employing selective SLC25A1 inhibitor or targeting mitochondrial OXPHOS dramatically reduced GPX4 expression and PDAC cell viability. Rescuing GPX4 expression with the products of both ACLY and ACO1-dependent pathways uncovered their critical role in conferring survival advantage under metabolic stress. Importantly, exogenous expression of GPX4 reversed redox imbalance and metabolic discordance resulting from the lack of SLC25A1 activity, indicating the requirement of citrate-induced GPX4 expression to support mitochondrial health and function. As observed with cultured cells under nutrient limitation, SLC25A1 function was revealed to be indispensable in pancreatic tumor microenvironment, and the reduced growth, due to the lack of SLC25A1 activity, was rescued with antioxidant NAC in preclinical models of PDAC. Lastly, SLC25A1 suppression was accompanied by elevated glutamine metabolism, and combination therapy with pharmacologic inhibitors of SLC25A1 and glutaminase inhibitor CB-839 dramatically suppressed tumor growth, highlighting this combinatorial approach as a potential therapeutic strategy in PDAC.
NimA promotes cell adhesion at the blood brain barrier ofDrosophilanervous system
Authors: Sakr Rosy , Monticelli Sara , Delaporte Claude , Zhang Gege , Tabiat Tarek , Giangrande Angela , Cattenoz Pierre B. 
Published: January 2025

AbstractGlial cells are crucial for nervous system development and function, by clearing debris, protecting neurons, and ensuring neuronal survival. In Drosophila, glia also form the blood-brain barrier (BBB), which regulates neural stem cell proliferation and shields the nervous system while maintaining organism-wide communication. To uncover glial-specific roles, we compared their transcriptome with that of neurons and macrophages.Our study identifies NimA, an uncharacterized member of the Nimrod scavenger receptor family, as a glial-specific protein consistently expressed during development. Unlike other family members, i.e. NimC1 (macrophage-specific), Draper (shared by glia and macrophages), and NimC4/Simu (restricted to embryonic stages), NimA is not involved in phagocytosis. Instead, it regulates cell-cell interactions and adhesion, crucial for maintaining the tight septate junctions of the larval BBB. Loss of NimA compromises BBB integrity, delays development, reduces brain size and impairs neural stem cell proliferation.Altogether, the identification of a novel molecular player and more in general, of the glial-specific molecular landscape, are key to understand the contribution of glia to the construction and the function of the nervous system.
Redundant, weakly connected prefrontal hemispheres balance precision and capacity in spatial working memory
Authors: Tschiersch Melanie , Umakantha Akash , Williamson Ryan C. , Smith Matthew A. , Barbosa Joao , Compte Albert 
Published: January 2025

AbstractHow the prefrontal hemispheres coordinate to adapt to spatial working memory (WM) demands remains an open question. Recently, two models have been proposed: A specialized model, where each hemisphere governs contralateral behavior, and a redundant model, where both hemispheres equally guide behavior in the full visual space. To explore these alternatives, we analyzed simultaneous bilateral prefrontal cortex recordings from three macaque monkeys performing a visuo-spatial WM task. Each hemisphere represented targets across the full visual field and equally predicted behavioral imprecisions. Furthermore, memory errors were weakly correlated between hemispheres, suggesting that redundant, weakly coupled prefrontal hemispheres support spatial WM. Attractor model simulations showed that the hemispheric redundancy improved precision in simple tasks, whereas weak inter-hemispheric coupling allowed for specialized hemispheres in complex tasks. This interhemispheric architecture reconciles previous findings thought to support distinct models into a unified architecture, providing a versatile interhemispheric architecture that adapts to varying cognitive demands.
Immune-sensitization toMycobacterium tuberculosisAmong Young Children With and Without Tuberculosis
Authors: Gutierrez Jesús , Malone LaShaunda L. , Mohammadi Mitchka , Mukisa John , Atuhairwe Michael , Mwesigwa Simon Peter G. , Athieno Salome , Buwule Sharon , Ameda Faith , Kiyingi Sophie , Mupere Ezekiel , Stein Catherine M. , Lancioni Christina L. 
Published: January 2025

ABSTRACTBackgroundIdentification of young children withMycobacterium tuberculosis(Mtb)-infection is critical to curb Tuberculosis (TB)-related pediatric morbidity and mortality. The optimal test to identify young children with evidence ofMtb-infection remains controversial.MethodsUsing a TB household contact (HHC) study design among 130 Ugandan children less than 5 years with establishedMtb-exposure, we compared the usefulness of the tuberculin skin test (TST) and QuantiFERON Gold Plus (QFT-Plus) to identify children with evidence forMtb-sensitization. We conducted univariate analysis to compare findings between children with and without TB disease, and performed a logistic regression model to estimate the odds of TB. We performed a sensitivity analysis by stratifying results by age (< 2 years vs. 2-5 years). Finally, we compared results of the QFT-Plus TB tube 1 and TB tube 2 to establish concordance.ResultsA 5 mm TST threshold identified the most children with evidence ofMtb-sensitization; this result was most pronounced in children with TB. Moreover, the odds of TB were 2 times higher [aOR: 2.09 (CI: 1.02 – 4.37)] among children with a positive TST. The QFT-Plus’ TB tube 1 and TB tube 2 results were highly correlated.ConclusionsTST identified more TB-exposed young children with evidence ofMtb-immune-sensitization, when compared to QFT-Plus. These findings are highly relevant for children who are TB HHCs in endemic settings, and most at risk for TB following an exposure. We recommend that TST testing continue to be performed to assess forMtb-sensitization in young children.
Tissue Region Segmentation in H&E-Stained and IHC-Stained Pathology Slides of Specimens from Different Origins
Authors: Naghshineh Kani Sepideh , Soyak Burak Can , Gokce Melih , Duyar Zeynep , Alicikus Hasan , Yapıcıer Özlem , Oner Mustafa Umit 
Published: January 2025

AbstractIn the era of advancing digital pathology, integrating digital slides and deep learning-based decision support systems has become increasingly prevalent in clinical practice. The effectiveness of these systems heavily relies on tissue region segmentation, a process essential for slide scanning and success of deep learning (DL) models. While thresholding-based methods are fast, they usually do not accurately detect tissue regions, especially in diverse staining scenarios or debris-laden images. Hence, this study develops a fast, lightweight, accurate, and robust deep-learning framework for segmenting tissue regions in digital pathology slides of various tissue types with different staining. The model is trained and tested on datasets of seven tissue types collected from seven different institutes. Internal and external validation studies have shown promising results, with area under receiver operating characteristics curve values greater than 0.98. The model has a memory footprint of 19.8 MBs, and it takes approximately 22 seconds to segment out a digital pathology slide using the CPU. The model could be used in digital slide scanners to improve the scanning process and in the pre-processing stages of DL pipelines to prepare high-quality datasets.
Berry Supplement-Modified Human Microbiome Improves Immunotherapy Response in Mouse Models
Authors: Jahanbahkshi Shiva , Bibi Amna , Hoyd Rebecca , Dravillas Caroline , Williams Nyelia , Zhang Shiqi , Pallerla Aaditya , Suman Shankar , Amann Joseph , Goruganthu Mounika , Okimoto Tamio , Liu Yangyang , Bittoni Marisa A. , Shi Ni , Anand Alvin , Conrad Bailey , Nevers Lane , Heitman Kristen , Webb Maxine , Grainger Elizabeth M , Grogan Madison , Quiles Christian , Chen Tong , Presley Carolyn J. , Li Lang , Bradley Patrick , Vodovotz Yael , Carbone David P. , Clinton Steven K. , Zhu Jiangjiang , Spakowicz Daniel 
Published: January 2025

AbstractCancer outcomes have improved with immune checkpoint inhibitor (ICI) treatment; however, less than half of tumors respond. Emerging data show that some responses to ICI depend on the host’s microbiome. Here, we explore a dietary intervention to modify the microbiome and determine the response to ICIs. Following pre-clinical studies showing the benefit of black raspberries, we conducted a human intervention trial called the BEWELL Study (NCT04267874). The intervention increased the abundance of pro-ICI-response microbes (PIRMs). In mouse models, participants’ post-dietary intervention stool led to smaller tumor volumes following treatment with ICIs than pre-dietary intervention samples. One PIRM,Blautia obeum, was sufficient to improve ICI response. These results suggest that black raspberry nectar can modify the human gut microbiome to promote an improved response to ICIs.
Association between digital biomarkers, loneliness and social isolation: a systematic review and meta-analysis
Authors: Lau Yolanda , Chemas Natalia , Gokani Heema Ajeet , Morrell Rachel , Phannarus Harisd , Cooper Claudia , Walker Zuzana , Demnitz-King Harriet , Marchant Natalie L 
Published: January 2025

ABSTRACTQuestionWhat is the current evidence base for the association between digital biomarkers from wrist-worn wearables, loneliness and social isolation in adults?Study selection and analysisWe systematically searched six databases from inception to 24thSeptember, 2024. We narratively synthesised findings and pooled effect sizes using random-effects meta-analyses where possible.FindingsWe included 14 studies from 12 articles (12 assessing loneliness, two assessing social isolation). Eight studies used sleep metrics, four used physical activity metrics, and two studies used machine learning approaches. Three meta-analyses were conducted: worse sleep efficiency (SE), but not total sleep time or sleep onset latency, was associated with higher loneliness (Fisher’s z = −0.20, 95% CI −0.34 to −0.06, p = 0.006). Two studies examined wake after sleep onset (WASO), and found longer periods of WASO were associated with higher loneliness. These findings on loneliness were echoed in the study examining social isolation. One study found that lower total physical activity was associated with higher levels of loneliness and social isolation, while other activity intensities showed mixed evidence. Machine learning studies demonstrated high accuracy in predicting loneliness, though models using digital biomarkers from smartphones provided better accuracy.ConclusionsWorse SE, more WASO, and lower total physical activity were associated with loneliness and social isolation, particularly in middle- and older-age. Digital biomarker-based machine learning studies are sparse but show potential in predicting loneliness. Leveraging digital biomarkers as proxy markers of loneliness and social isolation could facilitate early detection of these conditions.Key messages of the articlesWhat is already known on this topicLoneliness and social isolation are linked to negative health outcomes, including increased dementia risk. Digital biomarkers have shown potential in detecting mental health conditions and symptoms, but no systematic review has explored their association with loneliness and social isolation.What this study addsThis review identified 14 studies examining the association between digital biomarkers and loneliness or social isolation. Worse sleep efficiency, more wake after sleep onset, and lower physical activity were associated with higher levels of loneliness and social isolation.How this study might affect research, practice or policyDigital biomarkers could support the early detection of loneliness and social isolation, enabling timely intervention.
Detection of alpha synuclein seeding activity in tear fluid in patients with Parkinson’s disease
Authors: Canaslan Sezgi , Schmitz Matthias , Maass Fabian , Hermann Peter , da Silva Correia Susana , Zhang Shuyu , van Riesen Christoph , Parchi Piero , Lingor Paul , Zerr Inga 
Published: January 2025

AbstractDetection of alpha-synuclein seeding activity in tear fluid (TF) might provide a promising non-invasive biomarker for Parkinson’s disease (PD) diagnosis.In this study, we applied the alpha-synuclein seeding amplification assay (aSynSAA) to detect misfolded alpha-synuclein (aSyn) aggregation in TF from PD patients. The discovery cohort included 11 PD patients and 13 controls, and the validation cohort consisted of 9 PD patients and 11 controls without synucleinopathies.The aSynSAA yielded positive results in over 55% of PD patients. These findings were confirmed in a second cohort, including patients with prion diseases as a negative control for synuclein pathology. Our results demonstrate for the first time the ability of aSynSAA to distinguish between PD and control groups in TF, with PD showing the highest seeding activity compared to prion disease and control groups. Further comparisons between cerebrospinal fluid (CSF) and TF samples from the same individuals revealed consistent seeding results across both biofluids. These findings highlight the potential of tear fluid as a novel, accessible medium for detecting Lewy body-specific misfolded synuclein aggregation in PD, which could aid in early diagnosis and disease progression monitoring.
Individualized Alpha-tACS for Modulating Pain Perception and Neural Oscillations: A Sham-Controlled Study in Healthy Participants
Authors: Fathi Yaser , Dissassuca Françoise , Ricci Gloria , Liberati Giulia 
Published: January 2025

AbstractPain encompasses sensory, affective, and cognitive dimensions, with neural oscillations increasingly recognized as key mechanisms in their integration. However, the underlying processes remain inadequately understood. Transcranial alternating current stimulation (tACS) offers a promising tool for modulating these oscillations, yet the widespread reliance on ‘one-size-fits-all’ tACS protocols with fixed frequencies has led to limited and contradictory findings on its efficacy in pain treatment. In this study, we employed individualized tACS at individual peak alpha frequency (IAF) over the primary motor cortex (M1) contralateral to the dominant arm of 38 healthy participants, in a within-subject, sham-controlled design, to investigate its effects on pain perception and neural oscillations. Sustained and periodic 0.2 Hz thermonociceptive stimuli were applied to the dominant forearm before and after tACS. We measured participants pain perception and heat pain thresholds (HPT) before and after tACS stimulation. Scalp electroencephalography (EEG) measurements were used to measure neural activity during thermonociceptive stimuli. To calculate IAF, we used a discriminative approach based on independent component analysis (ICA) to separate sensorimotor related IAF (SM-IAF). The results revealed an overall increase in pain perception and a decrease in HPT in both sham and active conditions, with no significant interactions between conditions. However, a trend toward reduced sensitization post-tACS was observed. Exploratory analyses indicated a significant tACS effect on HPT in women. Furthermore, a significant correlation was found between SM-IAF and HPT. These findings provide a novel perspective on advancing individualized neuromodulation approaches for pain and neurobiological disorders.