bluuebunny/crossref_metadata_2025 huggingface dataset:
Dude, Everyone Wants Pattern Analysis Tools (DEWPAT): Tools for measuring visual pattern diversity from digital images
Authors: Sanderson Jillian A , Aumentado-Armstrong Tristan , Dufresne-Camaro Charles-Olivier , Mahler D Luke
Published: February 2025

Exploring the diversity and function of complex colour patterns is a fundamental interest in ecology and evolutionary biology, but progress on many questions is limited by our ability to quantify diverse visual patterns. We address this problem by introducing Dude, Everyone Wants Colour Pattern Analysis Tools (DEWPAT), a Python package for characterizing multidimensional pattern complexity.

DEWPATis a flexible framework designed to extract a diversity of components of visual pattern complexity from standard RGB and multispectral images, including entropy (information content), average gradient magnitude (edge content), high frequency content (detail granularity), generalized variance (heterogeneity), and patch dissimilarity.DEWPAToffers optional image transformation functionality, including blurring to model receiver acuity and segmentation to reduce noise.

Functions in this package return both quantitative measurements and graphical representations of color and pattern diversity. We demonstrateDEWPAT’s key functions and applications with three empirical examples (longhorn beetles, anole lizards, and flowers).

DEWPAThas the potential to quantitatively characterize previously intractable pattern phenotypes in ways that make their features available for biological analysis.
On CA1 ripple oscillations: reevaluating asynchronicity evidence
Authors: Scheffer-Teixeira Robson , Tort Adriano
Published: February 2025

Sharp-wave ripples (SWRs) are hippocampal network oscillations associated with memory consolidation. They are characterized by the co-occurrence of fast and slow field potentials across CA1 layers: the fast-frequency oscillations, known as ripples, are prominent in the pyramidal cell layer, where they coincide with increased neuronal spiking, while slower negative transients, referred to as sharp waves, occur simultaneously in thestratum radiatum. SWRs have traditionally been considered globally synchronous across the hippocampus; however, recent evidence suggests that ripples may be less synchronous than previously thought, particularly between the two hemispheres (Villalobos et al., 2017). In this study, we revisited this question using a unique dataset from probes spanning the septo-temporal axis of CA1. Our results demonstrate that ripples are phase-locked within but not between hemispheres, although their occurrence remains time-locked across both the septo-temporal axis and hemispheres. We also observed a similar synchronicity pattern for spiking activity: neurons are locally phase-coupled and globally time-coupled to ripple events. Interneurons exhibit a much stronger phase coupling to both ipsilateral and contralateral ripples than pyramidal neurons. These findings suggest that ripples are locally phase-coupled through pyramidal-interneuron interactions, with global time-locking likely driven by a common bilateral CA3 input and potentially modulated by interneuron circuits.
Decoding bacterial methylomes in four public health-relevant microbial species: Nanopore sequencing enables reproducible analysis of DNA modifications
Authors: Galeone Valentina , Dabernig-Heinz Johanna , Lohde Mara , Brandt Christian , Kohler Christian , Wagner Gabriel E. , Hölzer Martin
Published: February 2025

Investigating bacterial methylation profiles provides essential complementary information to the native DNA sequence, significantly extending our understanding of how DNA modifications influence virulence, antibiotic resistance, and the ability of bacteria to evade the immune system. Recent advancements in real-time Nanopore sequencing and basecalling algorithms have enabled the direct detection of modified bases from raw signal data, eliminating the need for bisulfite treatment of DNA. However, decoding methylation signals remains challenging due to rapid technological and methodological progress.

In this study, we focus on public health-relevant bacterial strains to analyze their methylation profiles and identify methylation motifs. Our dataset includes samples fromStaphylococcus aureus,Listeria monocytogenes,Enterococcus faecium, andKlebsiella pneumoniae, sequenced on the Nanopore GridION platform using the latest flow cell chemistry (R10.4.1) and modification basecalling models (Dorado basecalling SUP model v5).

We investigated distinct methylation patterns within and between species, focusing on heavily modified genes or genomic regions. Our results reveal distinct species-specific methylation profiles, with each strain exhibiting unique modification patterns. We developed a modular pipeline using Nextflow and the Nanopore Modkit tool to streamline the detection of methylated motifs. We compared the results with outputs from MicrobeMod, a recent toolkit for exploring prokaryotic methylation and base modifications in nanopore sequencing. Our pipeline is publicly available for further use (github.com/rki-mf1/ont-methylation).

We identified known methylation motifs already described in the literature and novelde novomotifs, providing deeper insights into the diversity of bacterial DNA modifications. Furthermore, we identified genomic regions that are extensively methylated, which could have implications for bacterial behavior and pathogenicity. We also assess improvements in basecalling accuracy, specifically how methylated bases can influence neighboring basecalls. Recent advances in basecalling models, particularly v5 models as part of Dorado, have reduced these issues, improving the reliability of methylation detection in bacterial genomes.

In conclusion, our study highlights the potential of current nanopore sequencing tools for detecting DNA modifications in prokaryotes. By making our pipeline and results publicly available, we facilitate further research into bacterial DNA modifications and their role in microbial pathogenesis.
Confounder-free Predictive Models for Microbiome-based Host Phenotype Prediction
Authors: Monshizadeh Mahsa , Hong Yuhui , Ye Yuzhen
Published: February 2025

As in many fields, the presence of confounding effects (or biases) presents a significant challenge in micro-biome research, including using microbiome data to predict host phenotypes. If not properly addressed, confounders can lead to spurious associations, biased predictions and misleading interpretations. One notable example is the medication metformin, which is commonly prescribed to treat type 2 diabetes (T2D) and is known to influence the gut microbiome. In this study, we propose confounder-free predictive models for human phenotype prediction using microbiome data. These models utilize an end-to-end approach within an adversarial min-max optimization framework to derive features that are invariant to confounding factors, while accounting for the intrinsic correlations between confounders and prediction outcomes. We implemented two versions of confounder-free predictors using different network architectures: one based on a fully connected network (referred as FNN CF) and another incorporating prior biological knowledge (referred as MicroKPNN CF). We evaluated our models on microbiome datasets associated with T2D, where metformin acts as a confounder. Our results demonstrate that confounder-free predictors achieve higher accuracy compared to models that do not account for confounders and more effectively identify microbial markers associated with the phenotype, rather than markers influenced by metformin. Between the two confounder-free models, although the prior-knowledge-guided approach showed slightly lower prediction accuracy compared to the fully connected model, it offered greater interpretability, providing additional insights into the underlying biological mechanisms.
Chronic Inhaled Benzene Exposure Exacerbates Atherosclerosis in LDL Receptor-Null Mice
Authors: Zelko Igor N. , Malovichko Marina V. , McFall Samantha A. , Taylor Breandon S. , Chen Hong , Conklin Daniel J. , Srivastava Sanjay
Published: February 2025

Background

Benzene is a ubiquitous environmental pollutant generated by a variety of natural and anthropological sources. It is a known carcinogen and hematopoietic toxin; however, little is known about benzene’s potential atherogenicity.

Hypothesis

Inhaled benzene induces atherogenesis by increasing vascular inflammation in LDL receptor Knockout (LDLR-KO) mice.

Methods

Male LDLR-KO mice were exposed to HEPA-filtered air or benzene (1 ppm, 6h/day, 5days/week) for 24 weeks. For the last 12 weeks of exposure, the mice were maintained on a western diet. The single nuclei RNA sequencing (snRNAseq) of aortae was performed at Novogene. Forin vitroexperiments, splenic naïve T cells were exposed to 1 µM of hydroquinone (HQ) for 24 hours, and intracellular ROR-gamma levels were measured by flow cytometry.

Results

Benzene inhalation increased the aortic valve lesion area by more than 25% (P<0.05) in LDLR-KO mice. Using snRNAseq, eleven major cell types were detected, including T cells and vascular smooth muscle cells (VSMC). Benzene increased the number of T cells by 2.5-fold, proliferating T-cells by 5.8-fold, and VSMC by 1.6-fold, suggesting increased cellularity and reduced plaque stability. In addition, benzene upregulated Th17 polarization markerRorcand negative regulators of apoptosisRag1andBcl11bwhile significantly attenuating the expression of proliferation inhibitorMs4a4bin T cells. In VSMC, benzene downregulated extracellular matrix organization genes and upregulated platelet degranulation pathways. Polarization of T cells into Th17 was confirmed by HQ-dependent upregulation of ROR-gammain vitro.

Conclusion

Our data suggest that inhaled benzene exposure compromises plaque cellularity and stability by facilitating T-cell proliferation and polarization, which coincides with the degradation of smooth muscle extracellular matrix and platelet activation.
The Influence of Macrophages within the Tumor Microenvironment on Ovarian Cancer Growth and Response to Therapies
Authors: Nikeghbal Parisa , Burke Danielle , Armijo Dalet , Aldarondo-Quinones Samuel , Lidke Diane S. , Steinkamp Mara P.
Published: February 2025

While the majority of ovarian cancer (OC) patients respond to front-line carboplatin/paclitaxel chemotherapy and surgical debulking, nearly all patients will develop platinum-resistance and recur. Our study investigates how tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) affect chemotherapy outcomes using OC patient-derived organoids and humanized patient-derived xenografts (huPDX).In vitromacrophage migration assays demonstrate the selective recruitment of M2 polarized macrophages to OC organoids. M2 macrophages, but not M1 macrophages, increase OC organoid viability and reduce their sensitivity to paclitaxel in co-culture assays. Furthermore, we identified BMS777607, a receptor tyrosine kinase inhibitor, that is capable of repolarizing M2 macrophagesin vitroand reduces organoid viability by a macrophage-dependent mechanism. In a platinum-sensitive humanized patient-derived xenograft (huPDX) model, the presence of human immune cells increased between-mouse variability in response to paclitaxel with two of four mice demonstrating tumor regrowth after two weeks of treatment. A TAM-targeted CSF-1R inhibitor, BLZ945 significantly reduced the total number of human immune cells within the ascites fluid of huPDX3 mice, but did not reduce tumor burden. However BLZ945 in combination with paclitaxel reduced tumor burden with no sign of regrowth. Our study demonstrates that patient-derived OC organoids and huPDX, are useful for evaluating the immunomodulatory effects of therapies and the influence of TAMs on response. huPDX models could serve as a robust platform for preclinical testing of novel anti-cancer treatments, providing insights into the complex interplay between immune cells and cancer therapeutics.
vcfsim: flexible simulation of all-sites VCFs with missing data
Authors: Goulart Paimon , Samuk Kieran
Published: February 2025

VCFs are the most widely used data format for encoding genetic variation. By design, standard VCFs do not include data from sites where all individuals are homozygous for the reference allele (“invariant sites”) and thus do not differentiate these from sites where data are completely missing. However, missing data are a key feature of biological datasets across all domains of genomics, and many recent studies have shown that missing data can introduce a variety of statistical biases in the estimation of key population genetic parameters. A solution to this limitation is to include invariant sites in a standard VCF, creating an “all-sites VCF”, exposing missing and invariant sites explicitly. One hurdle to the wider adoption of all-sites VCFs is a reliable parameterized simulation framework for generating biologically realistic all-sites VCFs. Here, we introduce an open-source command line tool,vcfsim, that interfaces with the popular coalescent simulation platformmsprimeand provides convenience functions for simulating all-sites VCFs with variable levels of ploidy and missing data. We show that the post-processed VCFs generated usingvcfsimalign precisely with population genetic expectations (i.e. are statistically identical to rawmsprimeoutput) and can accurately introduce missing data and varying ploidy levels, including the simulation of intraindividual ploidy variation (e.g. heterogametic sex chromosomes). We suggestvcfsimwill be a useful tool for the benchmarking of new software tools, training of machine learning models, and the exploration of the effects of missing data in genomics data sets.
User-Assisted Approach for Accurate Nonrigid Registration of Images and Traces
Authors: Baig Mirza M. Junaid , Hoang Tina Thuy N. , Chung Samuel H. , Stepanyants Armen
Published: February 2025

Fully automated registration algorithms are prone to getting trapped in solutions corresponding to local minima of their objective functions, leading to errors that are easy to detect but challenging to correct. Traditional solutions often involve iterative parameter tuning, data preprocessing and preregistering, and multiple algorithm reruns—an approach that is both time-consuming and does not guarantee satisfactory results. Therefore, for tasks where registration accuracy is more important than speed, it is appropriate to explore alternative, user-assisted registration strategies. In such tasks, finding and correcting errors in automated registration is often more time-consuming than directly integrating user input during the registration process.

Therefore, this study evaluates a user-assisted approach for accurate nonrigid registration of images and traces. By leveraging the corresponding sets of fiducial points provided by the user to guide the registration, the algorithm computes an optimal nonrigid transformation that combines linear and nonlinear components. Our findings demonstrate that the registration accuracy of this approach improves consistently with the increased complexity of the linear transformation and as more fiducial points are provided. As a result, accuracy sufficient for many biomedical applications can be achieved within minutes, requiring only a small number of user-provided fiducial points.
Lithographic structuring of thermoresponsive hydrogel on a micron scale
Authors: Esch Katharina , Zieske Katja
Published: February 2025

Hydrogel microstructures and microchannels are important tools in biophysical bottom-up approaches for studying the interactions between extracellular obstacles or boundaries and cells. In prior studies, several microstructuring techniques, cell sources, and gel types have been employed to mimic static cellular environments. However, the dynamic nature of the extracellular environment, which exerts forces on cells, plays an important role in tissue-level contexts. To date, only few approaches have been implemenmted to mimic these forces of the extracellular environment.

Here, we present an approach for generating arrays of hydrogel microstructures, that expand and contract dynamically in response to temperature modulations. To do this, we use a thermoresponsive hydrogel and a custom-built lithographic setup. Through direct lithographic photopatterning of a liquid phase, we fabricate smart hydrogel microstructures at the micrometer scale (10-100 μm) with well-defined geometries. These hydrogel microstructures display reversible size changes of over 70% triggered by temperature modulations.

Our study represents a step towards mimicking the dynamic properties of biological boundaries and obstacles. The dynamic nature of smart hydrogel microstructures holds the potential to mimic the micron-scale dynamics of extracellular environments. Our results may thus be relevant for the fields of bioengineering and systems level biophysics offering opportunities for manipulating and exploring cellular interactions with dynamic obstacles.
Competing Risk Model in Dental Cost-Effective Research
Authors: Seth Anand , Saleh Muhammad H.A. , Shah Priyanshi , Bhattacharyya Arinjita , Almashni Hamzeh , Troiano Guiseppe , Dukka Himabindu , Rai Shesh N.
Published: February 2025

Over the years, few attempts have been made to use survival analysis techniques in dental research. Moreover, the use of survival analysis was restricted to a simple method of drawing a survival curve using the Kaplan-Meier technique, but later prognostic factors were included utilizing the Cox Proportional Hazard (CPH) model. More recently, the CPH model has been incorporated with a frailty parameter to account for the correlation of observations within a subject. A recent publication has utilized a subdistribution hazard model with time-dependent covariates. In actual dental practice, a tooth failure could be due to a variety of reasons other than the cause of failure of interest. To have a realistic estimate of the risk of failure for cause i, one should also include the risk of failure due to causes j, j=1(1) n, which could occur prior to cause i. This competing risk scenario has been attempted in the last ten to fifteen years or so to estimate the probability of failure in the presence of competing event(s). Precise estimate of survival (failure) probabilities using competing risk model has implications in the dental cost-effectiveness and cost-utility studies.
Improving Labor Induction With Ultrasound: A Systematic Review
Authors: Romero Callejas Elisa , Enamorado Plata Antonio , Luque Fernández Miguel Ángel , Melchor Rodríguez Juan Manuel , Montero Alonso Miguel Ángel
Published: February 2025

Introduction

Labor induction is performed when continuing the pregnancy poses a greater risk than ending it. Elastography is emerging as an increasingly relevant technique to predict the success of labor induction.

Objective

To evaluate the relevant literature regarding elastography as a predictive tool for the success of labor induction, resulting in an uncomplicated vaginal delivery.

Methodology

A systematic review was conducted on the predictive accuracy of elastography in labor induction, using PubMed, Scopus, and the Cochrane Library. A total of 10 studies were selected, covering the period from 2007 to 2022. The included studies were clinical trials and observational studies that analyzed elastography in predicting the success of induced labor. Success was defined as the completion of labor via vaginal delivery without maternal or neonatal complications.

Results

The elastography technique demonstrates an increased accuracy in predicting successful labor induction and vaginal delivery compared to the traditional use of Bishop score. Among other predictors of labor induction failure, defined as labor ending in a cesarean delivery, are: cervical length (Odds Ratio [OR] OR = 1.916; 95% Confidence Interval [1.451–2.530]), maternal age ≥35 years, and body mass index (BMI) ≥30 kg/m2(OR = 2.257; 95% CI [1.353–3.767]). However, parity decreases the probability of labor induction failure (OR = 0.129; 95% CI [0.063–0.265]).

Discussion

The reviewed scientific evidence suggests that the use of elastography before induction improves the chances of a successful labor induction. Therefore, the right moment for the labor induction based on a clinical decision should be supplemented with other objective methods such as the elastography helping to evaluate the potential success of the induction and therefore, helping to improve maternal and infant health outcomes. Further research is recommended on the comparative effectiveness of different methods to identify the optimal time for labor induction, as well as to validate its clinical utility.
Meta-analysis reveals transcription factors and DNA binding domain variants associated with congenital heart defect and orofacial cleft
Authors: Jeong Raehoon , Bulyk Martha L.
Published: February 2025

Many structural birth defect patients lack genetic diagnoses because there are many disease genes as yet to be discovered. We applied a gene burden test incorporatingde novopredicted-loss-of-function (pLoF) and likely damaging missense variants together with inherited pLoF variants to a collection of congenital heart defect (CHD) and orofacial cleft (OC) parent-offspring trio cohorts (n = 3,835 and 1,844, respectively). We identified 17 novel candidate CHD genes and 10 novel candidate OC genes, of which many were known developmental disorder genes. Shorter genes were more powered in a “de novoonly” analysis as compared to analysis including inherited pLoF variants. TFs were enriched among the significant genes; 14 and 8 transcription factor (TF) genes showed significant variant burden for CHD and OC, respectively. In total, 30 affected children had ade novomissense variant in a DNA binding domain of a known CHD, OC, and other developmental disorder TF genes. Our results suggest candidate pathogenic variants in CHD and OC and their potentially pleiotropic effects in other developmental disorders.
Genomic Taxometric Analysis of Negative Emotionality and Major Depressive Disorder Highlights a Gradient of Genetic Differentiation across the Severity Spectrum
Authors: Ennis Garrett W. , Mallard Travis T. , de la Fuente Javier , Williams Camille M. , Schwaba Ted , Tucker-Drob Elliot M.
Published: February 2025

A core question in both human genetics and medicine is whether clinical disorders represent extreme manifestations of continuous traits or categorically distinct entities with unique genetic etiologies. To address this question, we introduceGenomic Taxometric Analysis of Continuous and Case-Controldata (GTACCC), a novel method for systematically evaluating continuity and differentiation of traits across the severity spectrum. GTACCC’s key innovation lies in binarizing continuous data at multiple severity thresholds, enabling the estimation of genetic continuity and differentiation within the trait and in its relation to other traits via multivariate models. We apply GTACCC to self-reported neuroticism data from UK Biobank (N= 414,448) and clinically ascertained major depressive disorder (MDD) data from the Psychiatric Genomics Consortium (ΣNeff = 111,221). We find that while neuroticism shares a considerable portion of its genetic etiology with MDD across the nonclinical, and even very low, range of (rg∼ .50), genetic sharing increases monotonically across the severity spectrum, approaching unity only at the highest levels of severity (rg∼ 1.0). Genomic structural equation models indicate that a single liability threshold model of negative emotionality is less consistent with the data than a multifactor model, suggesting that a gradient of genetic differentiation emerges across the spectrum of negative emotionality. Thus, within continuous measures of negative emotionality, partly distinct genetic liabilities exist at varying severity levels, with only the most severe levels associated with liabilities that approach equivalence to MDD genetics.
Low-concentration, low-dose lidocaine in ultrasound-guided sacral anesthesia reduces postoperative agitation and delirium in children undergoing hidden penis and hypospadias surgery: A prospective, randomized, controlled study
Authors: Guo Gaofeng , Wu Jiangxia , Zhao Yang , Zhang Jing , Yang Qing , Zhang Jiaqiang
Published: February 2025

Postoperative agitation or postoperative delirium (EA/ED) has a high incidence among pediatric patients undergoing anesthesia and surgery. In this study, we aimed to evaluate the effects of sacral anesthesia with 0.125 mL/kg of 1% lidocaine on EA/ED in children undergoing hidden penis and hypospadias surgery. Sixty children aged 1–6 years undergoing elective hidden penis or hypospadias surgery were enrolled in the study. The postoperative EA/ED score and incidence; Face, Legs, Activity, Cry, and Consolability scale; perioperative general information and vital signs; and the occurrence of adverse events were analyzed. Ultrasound-guided sacral anesthesia in children resulted in more stable vital signs, postoperative pain relief, fewer complications, and lower incidence of EA/ED. In conclusion, the use of 0.125 mL/kg of 1% lidocaine combined with laryngeal mask general anesthesia significantly reduced the incidence of EA/ED in children undergoing hidden penis and hypospadias surgery while ensuring high perioperative safety.
Classification of Pediatric Dental Diseases from Panoramic Radiographs using Natural Language Transformer and Deep Learning Models
Authors: Pham Tuan D.
Published: February 2025

Accurate classification of pediatric dental diseases from panoramic radiographs is crucial for early diagnosis and treatment planning. This study explores a text-based approach using a natural language transformer to generate textual descriptions of radiographs, which are then classified using deep learning models. Three models were evaluated: a one-dimensional convolutional neural network (1D-CNN), a long short-term memory (LSTM) network, and a pretrained bidirectional encoder representations from transformer (BERT) model for binary disease classification. Results showed that BERT achieved 77% accuracy, excelling in detecting periapical infections but struggling with caries identification. The 1D-CNN outperformed BERT with 84% accuracy, providing a more balanced classification, while the LSTM model achieved only 57% accuracy. Both 1D-CNN and BERT surpassed three pretrained CNN models trained directly on panoramic radiographs, indicating that text-based classification is a viable alternative to traditional image-based methods. These findings highlight the potential of language-based models for radiographic interpretation while underscoring challenges in generalizability. Future research should refine text generation, develop hybrid models integrating textual and image-based features, and validate performance on larger datasets to enhance clinical applicability.
Complexity of hospital demand during the COVID-19 pandemic in Mexico City
Authors: de Anda-Jáuregui Guillermo , Sifuentes-Osornio José , Angulo-Guerrero Ofelia , Díaz-De-León-Santiago Juan L , Benítez-Pérez Héctor , Herrera Luis A , López-Arellano Oliva , Revuelta-Herrera Arturo , Rosales-Tapia Ana R , Suárez-Lastra Manuel , Kershenobich David , Ruiz-Gutiérrez Rosaura , Hernández-Lemus Enrique
Published: February 2025

Background

The COVID-19 pandemic posed unprecedented challenges to healthcare systems worldwide. In densely populated urban areas such as Mexico City, the strain on hospitals was amplified due to the high volume of cases and resource limitations. Understanding the spatial and temporal dynamics of hospital demand is crucial for informing effective public health strategies and improving system resilience.

Methods

A retrospective analysis of COVID-19 hospitalization data in Mexico City was conducted utilizing a line-list dataset from the SISVER surveillance system. The analysis included the spatial distribution of hospital demand using the weighted centroid of hospitalizations as well as a model system of the interactions between residential areas and hospitals as a bipartite network. The emergence of giant components in the network was used as indicators of system strain and the relationship between network strain and patient outcomes was evaluated.

Findings

Hospital demand in Mexico City exhibited significant spatial dynamics, with a northward shift in the weighted centroid of hospitalizations as the pandemic progressed. Despite the changing distribution of cases, a small subset of 17 hospitals managed the majority of hospitalizations. During high-demand periods, the network transitioned to a more disordered state, characterized by a giant component encompassing multiple neighborhoods. This disordered strain was associated with higher case fatality rates, particularly in patients over 40 years of age.

Interpretation

Our findings highlight the complex, adaptive nature of the healthcare system in response to the pandemic. The emergence of giant components in the hospital demand network can serve as an early warning indicator of the health system overload. Adaptive measures, such as the establishment of temporary COVID-19 units, were effective in mitigating strain. These insights can guide future public health strategies for rapid response and resource allocation in similar crises.

Funding

This project was partially funded through CONACYT Project 320557 (to GA-J).
Hypertension Shifts Gut Microbiota and Tryptophan Metabolism in Women
Authors: Shah Shrushti , Mu Chunlong , Shen-Tu Grace , Schlicht Kristina , Forkert Nils , Laudes Matthias , Köfeler Harald , Shearer Jane
Published: February 2025

Background

Hypertension affects over 1.28 billion adults worldwide, including a significant number of women. Although the gut microbiome is implicated in the onset and progression of hypertension, few studies have examined the relationship in middle-aged women.

Methods

Within an established cohort, we investigated the relationship between gut microbiota and its metabolites in normotensive vs. hypertensive middle-aged women (n=108) matched for age (56.6±0.91 years) and body mass index (24.3±0.24 kg/m²). Fecal microbiota analysis was performed using 16S rRNA sequencing and serum metabolites were analyzed using LC-MS/QTOF. Associations between the microbiota, metabolomic alterations and systemic inflammatory cytokines were statistically examined to uncover their interrelationships and potential role in disease progression.

Results

Women with hypertension had gut dysbiosis with an increased Firmicutes/Bacteroidetes ratio and higher abundances of inflammatory taxa includingAnaerostipesandCollinsella. Untargeted serum metabolomics demonstrated that hypertensive participants had elevated levels of tryptophan, the pro-inflammatory metabolite kynurenine and lower levels of health-promoting indoles produced by the action of gut microbiota on tryptophan (p<0.05). These findings were confirmed in microbiota analysis showing a reduced abundance of indole-producing species (Alistipes shahii,Bacteroides faecichinchillae, Bacteroides stercoris)(p<0.05) suggesting a lower microbial activity of tryptophan-indole metabolism. Furthermore, hypertension increased inflammatory markers including an elevated IL12/IL10 ratio, interferon-γ and tumor necrosis factor-α. The IL-12/IL-10 ratio demonstrated a positive correlation with kynurenine levels, emphasizing the involvement of cytokines and gut microbiota in driving systemic inflammation in hypertension.

Conclusion

Imbalances in microbiota-regulated tryptophan metabolism contribute to systemic inflammation in hypertensive, middle-aged women, presenting a potentially modifiable target for intervention.

GRAPHICAL ABSTRACT
Sleep duration, physical activity and cardiometabolic multimorbidity: Findings from the English Longitudinal Study of Ageing
Authors: Kunutsor Setor K. , Laukkanen Jari A.
Published: February 2025

Background

U-shaped relationships have been demonstrated between sleep duration and several cardiometabolic conditions. However, the association between sleep duration and cardiometabolic multimorbidity (CMM) and the interrelationship with physical activity has not been previously investigated. We aimed to assess the prospective associations of sleep habits (duration and quality) with CMM and the interplay with physical activity.

Methods and Results

We included 3,428 participants (mean age 63 years at baseline, 44.8% male) free of hypertension, coronary heart disease, diabetes, and stroke at wave 4 from the English Longitudinal Study of Ageing. Sleep habits were assessed by self-reports. Cardiometabolic multimorbidity was defined as the presence of at least two multiple long-term conditions (hypertension, cardiovascular disease, diabetes, and stroke) at wave 10. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression models adjusted for established cardiometabolic risk factors including physical activity. At 15 years follow-up, 206 participants developed CMM. There was an approximate U-shaped trend between sleep duration and the risk of CMM. Compared to participants with sleep duration of 7-8 hrs/day, the multivariable OR (95% CI) for CMM was 1.39 (1.03-1.90) for sleep duration ≤6 hrs/day and 1.05 (0.55-2.00) for sleep duration ≥ 9 hrs/day. The odds of CMM modestly decreased for each additional hour increase in sleep duration in participants with sleep duration ≤6 hrs/day (OR, 0.78, 95% CI: 0.59-1.02). Sleep quality or physical activity was not associated with CMM.

Conclusions

Short sleep duration is associated with an increased risk of CMM, which is independent of established cardiometabolic risk factors including physical activity. Importantly, each additional hour of sleep among those with short sleep durations appeared to mitigate CMM risk, underscoring the potential benefits of optimizing sleep duration.
Dysregulation of cell migration by matrix metalloproteinases in geleophysic dysplasia
Authors: Morales Alejo A. , Camarena Vladimir , Peart LéShon , Smithson Sarah , Shaw Lindsay , Webber Lucy , Negron Jose M. , Sola Juan E. , Brady Ann-Christina , Walz Katherina , Wang Gaofeng , Tekin Mustafa
Published: February 2025

Geleophysic dysplasia (GD) is characterized by short stature, brachydactyly, joint limitations, a distinctive facial appearance, as well as cardiac and respiratory dysfunction that can be life-threatening. GD is caused by pathogenic variants in theADAMTSL2,FBN1,orLTBP3genes. While dermal fibroblasts derived from affected individuals have shown poor organization of the extracellular matrix (ECM), it remains elusive how the disorganized ECM contributes to GD pathogenesis. To understand the molecular mechanisms in GD, we isolated and characterized primary human dermal fibroblasts from affected individuals withADAMTSL2andFBN1variants. We found that the secretion of ECM proteins including ADAMTSL2, FBN1, and Fibronectin were impaired in GD fibroblasts. Increased cell migration was observed in GD fibroblasts carryingADAMTSL2orFBN1variants, which was associated with up-regulation of MMP-1 and MMP-14, two proteases related to cell mobility. The enhanced cell migration and up-regulation of MMP-1 and MMP-14 were corroborated in mouse primary dermal fibroblasts carrying pathogenic variants inAdamtsl2and in lung and heart tissues fromAdamtsl2-knockoutmice. A pan MMP inhibitor, GM6001, inhibited the migration of GD fibroblasts. Overall, our results suggest that MMP-1/-14 up-regulation play a role in the development of GD and may be utilized as a treatment target.
GeNePi: a GPU-enhanced Next Generation Bioinformatics Pipeline for Whole Genome Sequencing Analysis
Authors: Marangoni Stefano , Furia Federica , Charrance Debora , Fant Agata , Di Dio Salvatore , Trova Sara , Spirito Giovanni , Musacchia Francesco , Coppe Alessandro , Gustincich Stefano , Cavalli Andrea , Vecchi Manuela , Landuzzi Fabio
Published: February 2025

Next Generation Sequencing (NGS) has revolutionized genome biology, enabling the rapid sequencing of an entire human genome and facilitating the integration of Whole Genome Sequencing (WGS) into both research and clinical applications. The high-throughput nature of NGS and the complex data processing required has driven the need for advanced computational infrastructures to analyse these large datasets. The aim of this work is to introduce an innovative bioinformatic pipeline, named GeNePi, for the efficient and precise analysis of WGS short paired-end reads. Built on the Nextflow framework with a modular structure, GeNePi incorporates GPU-accelerated algorithms and supports multiple workflow configurations. The pipeline automates the extraction of biologically relevant insights from raw WGS data, including: disease-related variants such as single nucleotide variants (SNVs), small insertions or deletions (INDELs), copy number variants (CNVs), and structural variants (SVs). Optimized for high-performance computing (HPC) environments, it takes advantage of job-scheduler submissions, parallelised processing, and tailored resource allocation for each analysis step. Tested on synthetic and real datasets, GeNePi accurately identifies genomic variants, with performances comparable to that of state-of-art tools. These features make GeNePi a valuable instrument for large-scale analyses in both research and clinical contexts, representing a key step towards the establishment of National Centers for Computational and Technological Medicine.
Nora virus proliferates in dividing intestinal stem cells and sensitizes flies to intestinal infection and oxidative stress
Authors: Franchet Adrien , Haller Samantha , Yamba Miriam , Barbier Vincent , Thomaz-Vieira Angelica , Leclerc Vincent , Becker Stefanie , Lee Kwang-Zin , Orlov Igor , Spehner Danièle , Daeffler Laurent , Ferrandon Dominique
Published: February 2025

The digestive tract represents the most complex interface of an organism with its biotope. Food may be contaminated by pathogens and toxicants while an abundant and complex microbiota strives in the gut lumen. The organism must defend itself against potentially noxious biotic or abiotic stresses while preserving its microbiota, provided it plays a beneficial role. The presence of intestinal viruses adds another layer of complexity. Starting from a differential sensitivity of two lines from the sameDrosophilawild-type strain to ingestedPseudomonas aeruginosa, we report here that the presence of Nora virus in the gut epithelium promotes the sensitivity to this bacterial pathogen as well as to an ingested oxidizing xenobiotic. The genotype, age, nature of the ingested food and to a limited extent the microbiota are relevant parameters that influence the effects of Nora virus on host fitness. Mechanistically, we detect the initial presence of viral proteins essentially in progenitor cells. Upon stress such as infection, exposure to xenobiotics, aging or feeding on a rich-food diet, the virus is then detected in enterocytes, which correlates with a disruption of the intestinal barrier function in aged flies. Finally, we show that the virus proliferates only when ISCs are induced to divide and that blocking either enterocyte apoptosis or JAK/STAT-driven ISC division leads to a drastically reduced Nora virus titer.

In conclusion, it is important to check that experimental strains are devoid of intestinal viruses when monitoring survival/life span of fly lines or when investigating the homeostasis of the intestinal epithelium as these viruses can constitute significant confounding factors.
Platform-dependent effects of genetic variants on plasma APOL1 and their implications for kidney disease
Authors: Wang Qingbo S. , Huang Jinguo , Chan Leanne , Haste Nicole , Olsson Niclas , Gaun Aleksandr , McAllister Fiona , Madhireddy Deepthi , Baruch Amos , Melamud Eugene , Baryshnikova Anastasia
Published: February 2025

Mutations in apolipoprotein L1 (APOL1) are strongly associated with an increased risk of kidney disease in individuals of African ancestry, yet the underlying mechanisms remain largely unknown. Plasma proteomics provides opportunities to elucidate mechanisms of disease by studying the effects of disease-associated variants on circulating protein levels. Here, we examine the genetic drivers of circulating APOL1 in individuals of African and European ancestry from four independent cohorts (UK Biobank, AASK, deCODE and Health ABC) employing three proteomic technologies (Olink, SomaLogic and mass spectrometry). We find that disease-associatedAPOL1G1 and G2 variants are strong pQTLs for plasma APOL1 in Olink and SomaLogic, but the direction of their effects depends on the proteomic platform. We identify an additionalAPOL1missense variant (rs2239785), common in Europeans, exhibiting the same platform-dependent directional discrepancy. Similarly, variants in the kallikrein-kinin pathway (KLKB1,F12,KNG1) and their genetic interactions exhibit strongtrans-pQTL effects for APOL1 measured by Olink, but not SomaLogic. To explain these discrepancies, we propose a model in whichAPOL1mutations and the kallikrein-kinin pathway influence the relative abundance of two distinct APOL1 forms, corresponding to APOL1 bound to trypanolytic factors 1 and 2, which are differentially recognized by different proteomic platforms. We hypothesize that this shift in relative abundance of APOL1 forms may contribute to the development of kidney disease.
Evaluation of Protein Cards: A nutrition education tool for metabolic bariatric surgery
Authors: Acosta Patricia F.C. , Heidl Alexandra J. , Angeles Patricia M. , Farnesi Biagina-Carla , Alcindor Peggy , Alberga Angela S. , Erdstein Julius , Saputra Stephanie , Cohen Tamara R.
Published: February 2025

Background

Metabolic bariatric surgery (MBS) is a safe, effective treatment for severe obesity and its associated comorbidities. However, adherence to postoperative guidelines, particularly dietary protein intake remains a challenge. This study examined the suitability of theProtein Cards, a protein-focused nutrition education tool developed to support individuals meet their protein requirements during the postoperative diet stages: fluid, purée, soft, and regular diets.

Methods

An online adapted version of the Suitability Assessment of Materials questionnaire was administered from September 2020 to May 2021. Participants were recruited via convenience sampling and advertisement. The tool was rated as “superior”, “adequate” or “not suitable” on content, literacy demand, graphic illustrations, layout and typography, learning stimulation and motivation, and cultural appropriateness, with scores of 2, 1, and 0, respectively.

Results

A total of 442 individuals completed the online survey. Participants were identified as individuals who have undergone MBS (n= 268), caregivers of individuals who completed MBS (n =68), and/or healthcare providers specializing in MBS (n =106). TheProtein Cardsreceived an overall “superior” rating of 73.16%. The tool had a high likelihood of use particularly for the soft diet stage (63.98 ± 20.71). Participants preferred the tool be available as a mobile application (63.46 ± 20.44) followed by paper book (59.42 ± 22.12) format.

Conclusion

The development of nutrition education tools is essential for supporting individuals who have undergone MBS in adopting healthy dietary habits, particularly in their meeting protein requirements. Future studies will refine theProtein Cardsand evaluate its usability among individuals post-MBS.
Regional and national estimates of children affected by all-cause and COVID-19-associated orphanhood and caregiver death in Brazil, by age and family circumstance
Authors: Steyn Nicholas , Unwin H Juliette T , Ponmattam Jamie , Villaveces Andrés , Martins Luiza , Sherr Lorraine , Blenkinsop Alexandra , Semenova Elizaveta , Stuart-Brown Alice , Amaral André Victor Ribeiro , Ratmann Oliver , Schnekenberg Ricardo Parolin , Cluver Lucie , Hillis Susan , Rawlings Laura , Barberia Lorena , Souza Andrea Santos , Castro Marcia C , Flaxman Seth
Published: February 2025

Children affected by orphanhood of any cause may benefit from assessment and referral to appropriate services. Timely and accurate data can guide policy. We leveraged new data sources expanding previous reports on national COVID-19-associated orphanhood to estimate national and sub-national numbers of children newly affected by death of parents and co-residing elderly caregivers due to all-causes and to COVID-19-associated causes in 2020-2021 in Brazil.

We estimated that 1,300,000 (95% uncertainty interval 1,190,000, 1,430,000) children in Brazil experienced loss of one or multiple parents and/or co-residing caregivers 60+. 673,000 (652,000, 690,000) children were estimated to have lost one or both parents, of which 149,000 (144,000, 154,000) were COVID-19-associated; 635,000 (534,000, 758,000) children were estimated to have lost a co-residing grandparent or other kin, of which 135,000 (85,900, 199,000) were COVID-19-associated.

Orphanhood estimates varied across states. The highest all-cause rate of parental orphanhood was in Roraima, at 17.5 (95% uncertainty interval 15.6, 20.6) per 1000 children, and the lowest was in Santa Catarina, at 9.5 (8.7, 10.4) per 1000 children. COVID-19-associated orphanhood was also unevenly distributed, with Mato Grosso experiencing the greatest rate, at 4.4 (3.9, 5.3) per 1000 children, while Pará experienced the lowest rate of 1.4 (1.2, 1.8) per 1000 children.

We compared our estimates with administrative data for COVID-19-associated orphanhood (from Brazil’s civil registry offices and manually reviewed death certificates in Campinas) and found that a similar demographic distribution of orphanhood. However, our estimates suggested that administrative sources undercount orphanhood, suggesting that approximately 32% and 56% of total orphanhood was captured in the two datasets, respectively.

Our findings highlight the extent of orphanhood in Brazil and the large inequalities between states. Our comparisons with administrative data both validate our model and suggest that strengthening vital registration systems can put children at the center of public health responses globally.
Mini-Seizures: Novel Interictal iEEG Biomarker Capturing Synchronization Network Dynamics at the Epileptogenic Zone
Authors: Monsoor Tonmoy , Kanai Sotaro , Daida Atsuro , Kuroda Naoto , Sinha Prateik , Oana Shingo , Zhang Yipeng , Liu Lawrence , Singh Gaurav , Duan Chenda , Sim Myung Shin , Fallah Aria , Speier William , Asano Eishi , Roychowdhury Vwani , Nariai Hiroki
Published: February 2025

Epilepsy affects 1% of the population, with up to one-third of patients being medication-resistant. Surgery is the only curative treatment, yet over one-third of surgical patients fail to achieve seizure freedom due to the lack of a reliable epileptogenic zone (EZ) biomarker. We introduced and validated mini-seizures, frequent hypersynchronization events at EZ hubs that mirror seizure network dynamics, as a novel interictal EEG biomarker. Using a dynamical networks-based model, we analyzed short interictal intracranial EEG from 159 patients across two institutions. Our model, integrating hypersynchronous network properties and clinical data, successfully identified EZ hubs and accurately predicted one-year postoperative seizure outcomes. Our model (mean F1 score: 87%) outperformed the high-frequency oscillations-based model (mean F1 score: 79%) and seizure onset zone resection-status-based model (current clinical standard) (mean F1 score: 78%), supporting its potential as a robust interictal biomarker for EZ localization. Our findings suggest mini-seizures and seizures exist on a continuum of epileptic events, sharing common network properties. Unlike seizure-based analyses that require 1-2 weeks of monitoring to capture spontaneous seizures, mini-seizures provide a rapid alternative using only brief interictal recordings.
Long Covid in Older Adults: Functional Outcomes and Treatment Effectiveness
Authors: Wagner Brittin , Mathers Kate , Norfolk Aaron , Arora Tanishtha
Published: February 2025

We describe six-month functional status, hospitalization, and mortality among 23,632 cases of Long Covid in skilled nursing facilities (SNFs) in the US, primarily experienced by adults over 65 years old. We describe outcomes across seven medications used to treat Covid-19 including functional status (ADLs).