bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Review of Network Models for HIV Spread
Authors: Mattie Heather , Goyal Ravi , De Gruttola Victor , Onnela Jukka-Pekka 
Published: December 2024

Background:
HIV/AIDS has been a global health crisis for over 4 decades. Network models, which simulate human behavior and intervention impacts, have become an essential tool in guiding HIV prevention strategies and policies. However, no comprehensive survey of network models in HIV research has been conducted. This article fills that gap, offering a summary of past work and future directions to engage more researchers and inform policy related to eliminating HIV.

Setting:
Network models explicitly represent interactions between individuals, making them well-suited to study HIV transmission dynamics. Two primary modeling paradigms exist: a mechanistic approach from applied mathematics and a statistical approach from the social sciences. Each has distinct strengths and weaknesses, which should be understood for effective application to HIV research.

Methods:
We conducted a systematic review of network models used in HIV research, detailing the model types, populations, interventions, behaviors, datasets, and software used, while identifying potential future research directions.

Results:
Network models are particularly valuable for studying behaviors central to HIV transmission, such as partner selection and treatment adherence. Unlike traditional models, they focus on individual behaviors, aligning them with clinical practice. However, more accurate network data are needed for better model calibration and actionable insights.

Conclusions:
This article serves as a point of reference for HIV researchers interested in applying network models and understanding their limitations. To our knowledge, this is the most comprehensive review of HIV network models to date.
The Coexistence of Accessory Anterior Cerebral and Anterior Communicating Arteries
Authors: Triantafyllou George , Papadopoulos-Manolarakis Panagiotis , Tsakotos George , Piagkou Maria 
Published: December 2024

Variations in the cerebral artery circle are more prevalent than one might expect. This imaging report outlines the variability observed in the anterior circulation of a 47-year-old female patient, analyzed using a computed tomography angiogram. The first segments (A1) of the anterior cerebral arteries (ACAs) on the left and right side emanate from the internal carotid artery. The authors identified 2 anterior communicating arteries (AComAs) standing 1.4 mm apart. The left and right second segments (A2) of the ACAs were typically present, and authors discovered an accessory A2 branching from the second AComA, also referred to as the median artery of the corpus callosum. Consequently, the patient exhibited both accessories ACA and AComA. These morphological variants in the anterior cerebral circulation are particularly significant due to the increased risk of aneurysms in this area.
Linguistic and clinical validation of the Chinese version of the Acute Cystitis Symptom Score (ACSS) questionnaire in Taiwanese women with uncomplicated acute cystitis
Authors: Chou Yi-Ju , Chang Shang-Jen , Alidjanov Jakhongir F. , Naber Kurt G. , Yang Stephen Shei-Dei 
Published: December 2024

Purpose:
The Acute Cystitis Symptom Score (ACSS) questionnaire is designed to diagnose acute cystitis in women. By quantifying the severity of symptoms, ACSS provides objective diagnostic criteria. The aim of this study is to translate the ACSS questionnaire into a Chinese version and validate its clinical use for diagnosing acute cystitis in Taiwanese women.

Materials and methods:
After rigorously translating the ACSS questionnaire into traditional Chinese used by the Mandarin-speaking Taiwanese people, it was clinically validated. Women aged 20 and above with suspected acute cystitis were recruited as the patients, and healthy women undergoing health check-ups as controls. Discriminative ability was assessed by comparing ACSS scores between the 2 groups, and the optimal diagnostic cutoff was determined using receiver operating characteristics analysis. In the patient group, treatment response was evaluated as patient-reported outcome by comparing ACSS scores pretreatment and posttreatment.

Results:
A total of 89 and 43 participants were recruited for the patient and control groups, respectively. The total score of typical symptoms between the patient and the control groups was significantly different (P < 0.001). After antibiotic treatment, the total score of typical symptoms in the patient group significantly decreased (P < 0.001). Using receiver operating characteristics curve analysis, the best cutoff score for diagnosing acute cystitis was 4, with a sensitivity and a specificity of 75.3% and 95.3%, respectively.

Conclusion:
After clinical validation, the Chinese version of the ACSS questionnaire can now be used as a symptom-oriented diagnostic and patient-reported outcome tool for acute cystitis in the Mandarin-speaking female population in Taiwan.
EsoDetect: Computational Validation and Algorithm Development of a Novel Diagnostic and Prognostic Tool for Dysplasia in Barrett’s Esophagus
Authors: Miskinyte Migla , Pondeca Benilde , Pereira-Leal José B. , Cardoso Joana 
Published: December 2024

ABSTRACTBarrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a malignancy with increasing incidence and unfavorable prognosis. This study endeavors to identify BE biomarkers capable of diagnosing low-grade dysplasia (LGD) in BE, as well as biomarkers that can predict the progression from BE to EAC to be subsequently integrated into diagnostic and prognostic algorithms.Datasets containing gene expression data from metaplastic and dysplastic BE, as well as EAC tissue samples, were collected from public databases and used to explore gene expression patterns that differentiate between non-dysplastic (ND) and LGD BE (for diagnostic purposes) and between non-progressed and progressed BE (for prognostic purposes). Specifically, for the diagnostic application, three RNAseq datasets were employed, while for the prognostic application, nine microarray datasets were identified, and 25 previously described genes were validated. A Thresholding Function was applied to each gene to determine the optimal gene expression threshold for group differentiation. All analyzed genes were ranked based on the F1-score metrics. Following the identification of genes with superior performance, different classifiers were trained. Subsequently, the best algorithms for diagnostic and prognostic applications were selected.In evaluating the value of gene expression for diagnosis and prognosis, the analyzed datasets allowed for the ranking of biomarkers, resulting in eighteen diagnostic genes and fifteen prognostic genes that were used for further algorithm development. Ultimately, a linear support vector machine algorithm incorporating ten genes was identified for diagnostic application, while a radial basis function support vector machine algorithm, also utilizing ten genes, was selected for prognostic prediction. Notably, both classifiers achieved recall and specificity scores exceeding 0.90.The identified algorithms, along with their associated biomarkers, hold significant potential to aid in the early management of malignant progression of BE. Their strengths lie in their development using multiple independent datasets and their ability to demonstrate recall and specificity levels superior to those reported in the existing literature. Ongoing experimental and clinical validation is essential to further substantiate their utility and effectiveness, and to ensure that these tools can be reliably integrated into clinical practice to improve patient outcomes.
Implementing the mhGAP-HIG: The process and outcome of supervising trained primary health care workers in Khyber Pakhtunkhwa, Pakistan
Authors: Humayun Asma , Najmussaqib Arooj , Muneeb Noor ul Ain 
Published: December 2024

AbstractBackgroundThe province of Khyber Pakhtunkhwa (KP), grappling with frequent humanitarian and conflict challenges, faces significant gaps in mental health services marked by limited resources and inequitable distribution of services. To strengthen these services in nine districts in the province, 105 PHCWs were trained to identify and treat psychological conditions and were subsequently supervised for three months. This study examined the efficacy of remote supervision and analyzed the clinical data gathered during the supervision period.MethodsA mixed-method approach was used to collect clinical data during supervision. Supervision covered assessment, management (including pharmacological and psychosocial interventions), and referral needs in all cases. Both qualitative and quantitative feedback were analyzed. Additionally, clinical data were examined to identify reported stressors and clinical presentations.ResultsOut of 105 registered trainees, 53 (50.34%) participants (including 38 PCPs and 15 CPs) submitted 413 cases through the application during three months of supervision following the initial training. The most frequently reported condition was depression (56.9%). Commonly reported stressors include health challenges or caregiver burden, marital or domestic challenges, bereavement, and socio-economic difficulties. Supervision was crucial in adjusting diagnoses in nearly a quarter of cases and management plans in 38.25% of cases. Participants expressed a preference for remote supervision and found it beneficial for assessment/diagnosis (61.1%), management interventions (72.2%), and referral guidance (44.4%).ConclusionEffective capacity building of PHCWs depends on remote supervision for an extended period, continuous monitoring of assessment and intervention skills, and the establishment of structured referral pathways. The collection of clinical data is crucial for improving the training programs. Systematic support from provincial governments is essential to scale up this initiative.
Bulk Transcriptomic Analysis with InMoose, the Integrated Multi-Omic Open-Source Environment in Python
Authors: Colange Maximilien , Appé Guillaume , Meunier Léa , Weill Solène , Johnson W. Evan , Nordor Akpéli , Behdenna Abdelkader 
Published: December 2024

AbstractWe introduce InMoose, an open-source Python environment aimed at omic data analysis. We illustrate its capabilities for bulk transcriptomic data analysis.Due to its wide adoption, Python has grown as ade factostandard in fields increasingly important for bioinformatic pipelines, such as data science, machine learning, or artificial intelligence (AI). As a general-purpose language, Python is also recognized for its versatility and scalability. InMoose aims at bringing state-of-the-art tools, historically written in R, to the Python ecosystem. Our intent is to provide a drop-in replacement for R tools, so our approach focuses on the faithfulness to the original tools outcomes. The first development phase has focused on bulk transcriptomic data, with current capabilities encompassing data simulation, batch effect correction, and differential analysis and meta-analysis.
Knowledge Graph and Machine Learning Help the Research of Drugs Aimed at Neurological Diseases
Authors: Menestrina Luca , Recanatini Maurizio 
Published: December 2024

AbstractIn this study, we present PATHOS (PATHologies of HOmo Sapiens), a semantically rich knowledge graph constructed by integrating diverse datasets spanning multiple biomedical entity types. PATHOS provides a comprehensive resource for representing and exploring the intricate relationships underlying human diseases. To leverage this resource, we developed LOGOS (Learning Optimized Graph-based representations of Object Semantics), a graph embedding model capable of generating predictions relevant to drug research. The PATHOS-LOGOS framework was validated through three neurological case studies: drug repurposing for Alzheimer’s disease, phenotype selection for Huntington’s disease, and protein target identification in multiple sclerosis. The results demonstrate the potential of this approach to advance therapeutic insights and inform biomedical research.
Rebuilding the autoimmune-damaged corneal stroma through topical lubrication
Authors: Efraim Yael , Ting Chen Feeling Yu , Niknezhad Seyyed Vahid , Pham Dylan , Cheong Ka Neng , An Luye , Sinada Hanan , McNamara Nancy A. , Knox Sarah M. 
Published: December 2024

AbstractCorneal lubrication is the most common treatment for relieving the signs and symptoms of dry eye and is considered to be largely palliative with no regenerative functions. Here we challenge this notion by demonstrating that wetting the desiccated cornea of an aqueous-deficient mouse model with the simplest form of lubrication, a saline-based solution, is sufficient to rescue the severely disrupted collagen-rich architecture of the stroma, the largest corneal compartment that is essential to transparency and vision. At the single cell level we show that stromal keratocytes responsible for maintaining stromal integrity are converted from an inflammatory state into unique reparative cell states by lubrication alone, thus revealing the extensive plasticity of these cells and the regenerative function of lubricating the surface. We further show that the generation of a reparative phenotype is due, in part, to disruption of an IL1β autocrine amplification loop promoting chronic inflammation. Thus, our study uncovers the regenerative potential of topical lubrication in dry eye and represents a paradigm shift in our understanding of its therapeutic impact.
PD-L1 expression is mediated by microRNA processing, Wnt/β-catenin signaling, and chemotherapy in Wilms tumor
Authors: Desai Kavita , Tiburcio Patricia D.B. , Warne Austin , Nabbi Arash , Zhou Serena , Reiff Sean D. , Campbell Matthew E. , Chen Kenneth S. 
Published: December 2024

ABSTRACTInhibition of immune checkpoint proteins is effective in adult cancers but has shown limited efficacy in pediatric cancers. While factors regulating expression of immune checkpoint proteins such as PD-L1 are well-documented in adult cancers, their regulation is poorly understood in pediatric cancers. Here, we show that PD-L1 is upregulated in distinct subsets of Wilms tumor, the most common pediatric kidney cancer. Specifically, chemotherapy-exposed Wilms tumor specimens exhibited higher levels of PD-L1 expression, and common chemotherapeutics upregulated PD-L1 in childhood cancer cell linesin vitro. Furthermore, mutations inCTNNB1andDROSHA, the two most commonly mutated genes in Wilms tumor, correlated with higher PD-L1. Activation of Wnt/β-catenin signaling and knockdown ofDROSHAorDICER1both increase PD-L1in vitro. Lastly, in adult cancers,DICER1alterations are associated with immune gene expression signatures and improved survival in response to immune checkpoint inhibitors. Together, our results identify clinical and biological properties regulating PD-L1 in Wilms tumor that may inform precision therapy approaches in pediatric immuno-oncology.
FCRL4 and exhausted B cell signature in tumor infiltrating B cells from lung cancer
Authors: Bryushkova EA , Shchoka EV , Lukyanov DK , Gikalo MB , Mushenkova N , Laktionov K.K. , Kazakov A.M. , Khalmurzaev O.A , Matveev V.B. , Chudakov DM , Serebrovskaya EO 
Published: December 2024

AbstractOur understanding of the heterogeneity of tumor-infiltrating B cells (TIBs) evolves in parallel with the advances in high-dimensional flow cytometry and single-cell RNA sequencing (scRNA-seq). Subpopulations of TIBs have been described with diverse and even opposite roles in tumor control, based on surface molecule, cytokine and transcriptional factor expression. Furthermore, recently the predictive role of IgA and IgG expression in tumors was shown for melanoma and KRAS-mutated, but not KRAS wild type, lung adenocarcinoma. This may imply that B cells producing different immunoglobulin isotypes also acquire different functional characteristics that have unequal effects on tumor microenvironment (TME) and differentially affect tumor progression. To address this question, we performed comparative bulk transcriptome analysis of tumor-infiltrating surface-IgA+ (sIgA+) and sIgG+ memory B cells from lung adenocarcinoma (LUAD) tumors. We identified FCRL4, PDCD1 and RUNX2 among genes overexpressed in IgA+ B cells, which suggests exhausted, chronically antigen-stimulated phenotype. Using public scRNA-seq data, we showed that FCRL4-expressing memory TIBs form a distinct cluster of cells with transcriptomic profile characterized by upregulation of genes involved in IFNγ and IFNα responses. sIgG+ B cells, on the other hand, overexpress IL5RA, consistent with the role of IL-5 in class-switch recombination to IgG isotype. Moreover, based on the analysis of the TCGA LUAD cohort, we found that FCRL4 to CD20 expression ratio correlates with lower overall survival, further strengthening the view on FCRL4 as a marker of exhausted dysfunctional TIBs. Our findings support the initial hypothesis that IgA/IgG ratio in tumors is not merely an indication of cytokine environment in the TME, but also reflects the difference in the functional characteristics of the respective B cell populations.
Vaginal Microbiome and Inflammation Among Chinese Women
Authors: Yichan Zhang , Ina Schuppe-Koistinen , Huarui Wang , Vicente Pelechano Garcia , Xiangyang Tian , Wei-Hua Chen , Guolan Gao , Juan Du 
Published: December 2024

AbstractHuman papillomavirus (HPV) infection, cervical intraepithelial neoplasia (CIN), pelvic organ prolapse (POP), cervical polyps (CP), abnormal uterine bleeding (AUB), and vaginitis are common conditions encountered in gynecological practice. In this study, we collected vaginal secretions from patients diagnosed with these diseases (n = 310) and from healthy donors (n = 112) to analyze their vaginal microbiome using 16S rRNA sequencing and cytokine expression using a cytometric bead array (CBA). Our findings revealed that the vaginal microbiome in POP patients exhibited higher complexity compared to other groups. Regarding cytokine expression, levels of IL-1α, IL-1β, IL-6, IL-8, MCP-1, and MIG were significantly elevated in HPV and CIN patients. Analysis of microbial associations showed thatLactobacillus crispatusandLactobacillus inerswere significantly negatively correlated with IL-1α and IL-1β expression. In contrast, non-Lactobacillusbacteria, includingBifidobacterium breve, Prevotella bivia, Gardnerella vaginalis, Sneathia amnii, Sneathia sanguinegens, Prevotella amnii, Escherichia coli,andChlamydia trachomatis, were positively correlated with IL-1α, IL-1β, IL-6, IL-8, MCP-1, and MIG levels. Furthermore,Lactobacillus inersexhibited a significant negative effect in the HPV and CIN patient groups.
Temporal Lobe Epilepsy is dominated by Region Specific Interictal Cortical Inhibition
Authors: Kienitz Ricardo , Strzelczyk Adam , Spyrantis Andrea , Konczalla Jürgen , Rosenow Felix , Strüber Michael 
Published: December 2024

AbstractEpilepsy is typically characterized by excessive neuronal excitability, manifesting as seizures and interictal epileptiform discharges (IEDs) in the EEG. However, the dynamics of excitation and inhibition (E/I balance) remain poorly understood. Here, we leverage the aperiodic exponent of the EEG power spectrum—a marker indicative of synaptic inhibition—to investigate shifts in E/I balance during antiseizure medication (ASM) tapering in patients with mesial temporal lobe epilepsy (TLE). We analyzed EEG data from 28 TLE patients and 25 controls with non-epileptic episodes (NEE) undergoing presurgical video EEG monitoring. Unexpectedly, TLE patients showed a localized increase in the aperiodic exponent in the ipsilesional temporal lobe during ASM tapering, absent in controls. This inhibition increase correlated with seizure latency and predicted seizure occurrence. Intracranial recordings from 10 TLE patients revealed higher aperiodic exponents in the lateral temporal cortex compared to the hippocampus, suggesting stronger inhibition in the lateral cortex. Notably, hippocampal IEDs triggered transient inhibitory responses in the lateral cortex, accompanied by increased high-frequency activity and disrupted hippocampus-to-lateral connectivity. These findings suggest that TLE likely involves complex inhibitory mechanisms beyond the epileptic focus in the interictal period, with neocortical inhibition potentially containing epileptic activity, and offers a new tool to map epileptic brain regions.
Does domestication trade-off stress tolerance for leaf growth? A search for evidence across eight Pooideae grass species
Authors: Yun Jie , Yuan Chenyang , Irelan Katherine , Kabongo MJ , Urkumbayev Eldar , Des Marais David L. 
Published: December 2024

AbstractPlant domestication is thought to create trade-offs between high yield and stress tolerance, raising concerns about yield stability in future climates. Previous studies have found limited direct evidence for such trade-offs, often focusing on weakened defenses associated with higher growth rates. However, trade-offs can also occur when traits (such as yield in agriculture) optimized for favorable conditions perform less efficiently in stressful conditions. Deciphering the mechanisms driving these trade-offs is crucial for maintaining yield in changing environments. We examine leaf growth, a key trait influencing carbon assimilation, in eight species of grasses. We use a machine learning pipeline to automatically extract cell dimensions and positions from leaf microscope images to study cell kinematics, finding that domesticated plants generally have longer leaves, larger division zones and higher cell production rates. We found no clear evidence of trade-off between domestication and drought response in final leaf length. However, a trade-off is observed in development as wild species exhibited a smaller decrease in elongation zone size under drought than their domesticated counterparts. These nuanced trade-offs associated with domestication highlight the importance of examining physiological traits and mechanisms in greater detail, possibly informing breeding strategies to enhance crop resilience in the face of climate change.HighlightThis study uses a high throughput pipeline to characterize leaf elongation responding to drought stress across eight species including barley, wheat, oat and wild relatives.