bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling-Up the Impact of Teledermoscopy on the Early Detection of Skin Melanoma using Convolutional Neural Networks with Mobile Apps
Authors: Tyagi Tejasvi , Vempati Swati Mathur , Upadhyay Kshitiz 
Published: September 2024

AbstractAdvances in the cloud technology for secured distributed data storage, modern techniques for machine learning (ML), and access to large populations through mobile apps provide a unique opportunity for the healthcare industry professionals in the areas of early screening and medical diagnostics for certain diseases. This research study demonstrates the potential of ML using convolutional neural networks (CNN) for medical diagnostics of skin melanoma. Specifically, a comparison is presented between a shallow CNN (3-layers) with Resnet50 (50-layers) to classify open datasets of skin melanoma images as malignant or benign. Various ML performance metrics such as accuracy, recall, precision and receiver operating characteristic (ROC) are presented to recommend a deep learning model for the mobile app. Also, a novel framework is proposed for the scalability and adoption of ML-based medical diagnostics by large masses as a mobile app running on data-secure cloud platform. Using the open datasets, it is shown that skin cancer can be accurately diagnosed with a mobile phone app while maintaining patient privacy and data security.
Multi-ancestry population attributable risk assessment of common genetic variation in Alzheimer’s and Parkinson’s diseases
Authors: Jones Lietsel , Cerquera-Cleves Catalina , Schuh Artur FS , Makarious Mary B , Iwaki Hirotaka , Nalls Mike A. , Noyce Alastair J ,   Global Parkinson’s Genetics Program (GP2), Blauwendraat Cornelis , Singleton Andrew , Mata Ignacio , Bandres-Ciga Sara 
Published: September 2024

AbstractMultiple scientific studies, mostly performed within European populations, have unraveled many of the genetic factors associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD) etiologies, improving our understanding of the molecular pathways implicated in the pathogenesis of these conditions. However, there is increasing evidence that the genetic architecture of these diseases differs across ancestral populations. This raises concerns about the efficacy of therapeutic interventions crafted around genetic targets prevalent only in European ancestry populations. Such interventions neglect potentially distinctive etiological profiles, including Latino, Black/African American, and East Asian populations. In the current study, we explore Population Attributable Risk (PAR) in AD and PD etiologies and assess the proportion of disease attributed to specific genetic factors across diverse populations. Leveraging data from genome-wide association studies across four ancestries, we explore distinct and universal therapeutic targets across diverse populations. Multi-ancestral genetics research is critical to the development of successful therapeutics and treatments for neurodegenerative diseases. By offering insights into genetic disparities, we aim to inform more inclusive and effective therapeutic strategies, advancing personalized healthcare.
Comprehensive Sequencing of Environmental RNA from Japanese Medaka at Various Size Fractions and Comparison with Skin RNA
Authors: Hiki Kyoshiro , Jo Toshiaki S. 
Published: September 2024

ABSTRACTEnvironmental RNA (eRNA) is emerging as a non-invasive tool for assessing the health of macro-organisms, but key information on its origin and particle sizes remains unclear. In this study, we performed comprehensive RNA-sequencing of eRNA (> 13 Gb/sample) collected from tank water containing Japanese medaka (Oryzias latipes), using sequential filtration through filters with pore sizes of 10, 3, and 0.4 μm. Fish skin RNA was also sequenced to reveal the origin of eRNA. Our results showed that the 3−10 μm fraction contained the lowest relative abundance of microbial RNA, the highest amount of medaka eRNA, and the largest number of detected medaka genes (5398 genes), while the 0.4−3 μm fraction had the fewest (972 genes). Only a small number of genes (42 genes) were unique to the 0.4−3 μm fraction. These findings suggest that a 3 μm filter is optimal for eRNA analysis, as it allows for larger filtration volumes while maintaining the relative abundance of macro-organism eRNA. Furthermore, 81% of the genes detected in eRNA overlapped with skin RNA, indicating skin is a major source of fish eRNA.SynopsisThe 3 µm filter is recommended to maximize the detection of eRNA from macro-organisms while reducing the relative abundance of microbial RNA.TOC Art
GDF3 promotes adipose tissue macrophage-mediated inflammation via altered chromatin accessibility during aging
Authors: Jang In Hwa , Kruglov Victor , Cholensky Stephanie H. , Smith Declan M. , Carey Anna , Bai Suxia , Nottoli Timothy , Bernlohr David A. , Camell Christina D. 
Published: September 2024

ABSTRACTAge-related susceptibility to sepsis and endotoxemia is poorly defined, although hyperactivation of the immune system and the expansion of the visceral adipose as an immunological reservoir are underlying features. Macrophages from older organisms exhibit substantial changes, including chronic NLRP3 inflammasome activation, genomic remodeling and a dysfunctional, amplified inflammatory response upon new exposure to pathogen. However, the mechanisms by which old macrophages maintain their inflammatory phenotype during endotoxemia remains elusive. We previously identifiedGdf3, a TGFβ superfamily cytokine, as a top-regulated gene by age and the NLRP3 inflammasome in adipose tissue macrophages (ATMs). Here, we demonstrate that endotoxemia increases inflammatory (CD11c+) ATMs in aGdf3-dependent manner in old mice. Lifelong systemic or myeloid-specific deletion ofGdf3leads to reduced endotoxemia- induced inflammation, with decreased CD11c+ATMs and inflammatory cytokines, and protection from hypothermia. Moreover, acute blockade ofGdf3using JQ1, a BRD4 inhibitor, phenocopies old mice with lifelongGdf3-deficiency. We show that GDF3 promotes the inflammatory phenotype in ATMs by phosphorylating SMAD2/3. Mechanistically, the differential chromatin landscape of ATMs from old mice with or without myeloid-drivenGdf3indicates that GDF3- SMAD2/3 signaling axis shifts the chromatin accessibility of ATMs towards an inflammatory state during aging. Furthermore, pharmaceutical inhibition of SMAD3 with a specific inhibitor of SMAD3 (SIS3) mimicsGdf3deletion. SIS3 reduces endotoxemia-mediated inflammation with fewer CD11c+ATMs and less severe hypothermia in old, but not young mice, as well as reduced mortality. In human adipose tissue, age positively correlates withGDF3level, while inflammation correlates with pSMAD2/3 level. Overall, these results highlight the importance of GDF3-SMAD2/3 axis in driving inflammation in older organisms and identify this signaling axis as a promising therapeutic target for mitigating endotoxemia-related inflammation in the aged.
Mapping genomic regions associated with temperature stress in the wheat pathogenZymoseptoria tritici
Authors: Stapley Jessica , Zhong Ziming , McDonald Bruce A. 
Published: September 2024

AbstractClimate change can alter interactions between plants and their pathogens, which could adversely affect crop production. To better understand the molecular mechanisms underlying the responses of pathogenic fungal to temperature stress, we conducted a quantitative trait loci (QTL) mapping study in the wheat pathogenZymoseptoria triticito identify genomic regions associated with colony growth and melanisation at three temperatures (10°C, 18°C, 27°C). We then identified likely candidate genes for thermal adaptation within these intervals by combining information regarding gene function, GO annotation enrichment, transcriptional profile, and results from previous genome wide association studies (GWAS) investigating responses to climate, temperature and thermal adaptation. The QTL mapping, conducted for two separate crosses involving four Swiss parents, found significant QTL uniquely associated with traits measured in high and low temperatures. These intervals contained many genes known to regulate responses to temperature stress, including heat shock proteins (HSPs) and proteins involved in the mitogen-activated protein kinase (MAPK) pathways, and were enriched for genes with a zinc ion binding GO annotation. We highlight the most promising candidate genes for thermal adaptation, including an ammonium transporter gene, a stress response factor (Whi1) and two MAPK pathway genes -SSk2andOpy2. Future validation work on these candidate genes could provide novel insight into the molecular mechanisms underlying temperature adaptation in this important wheat pathogen.
Hydrogels with Independently Controlled Adhesion Ligand Mobility and Viscoelasticity Increase Cell Adhesion and Spreading
Authors: Moghaddam Abolfazl Salehi , Dunne Katelyn , Breyer Wendy , Wu Yingjie , Pashuck E. Thomas 
Published: September 2024

AbstractA primary objective in designing hydrogels for cell culture is recreating the cell-matrix interactions found within human tissues. Identifying the most important biomaterial features for these interactions is challenging because it is difficult to independently adjust variables such as matrix stiffness, stress relaxation, the mobility of adhesion ligands and the ability of these ligands to support cellular forces. In this work we designed a hydrogel platform consisting of interpenetrating polymer networks of covalently crosslinked poly(ethylene glycol) (PEG) and self-assembled peptide amphiphiles (PA). We can tailor the storage modulus of the hydrogel by altering the concentration and composition of each network, and we can tune the stress relaxation half-life through the non-covalent bonding in the PA network. Ligand mobility can be adjusted independently of the matrix mechanical properties by attaching the RGD cell adhesion ligand to either the covalent PEG network, the dynamic PA network, or both networks at once. Interestingly, our findings show that endothelial cell adhesion formation and spreading is maximized in soft, viscoelastic gels in which RGD adhesion ligands are present on both the covalent PEG and non-covalent PA networks. The dynamic nature of cell adhesion domains, coupled with their ability to exert substantial forces on the matrix, suggests that having different presentations of RGD ligands which are either mobile or are capable of withstanding significant forces are needed mimic different aspects of complex cell-matrix adhesions. By demonstrating how different presentations of RGD ligands affect cell behavior independently of viscoelastic properties, these results contribute to the rational design of hydrogels that facilitate desired cell-matrix interactions, with the potential of improvingin vitromodels and regenerative therapies.
ELLA: Modeling Subcellular Spatial Variation of Gene Expression within Cells in High-Resolution Spatial Transcriptomics
Authors: Wang Jade Xiaoqing , Zhou Xiang 
Published: September 2024

AbstractSpatial transcriptomic technologies are becoming increasingly high-resolution, enabling precise measurement of gene expression at the subcellular level. Here, we introduce a computational method called subcellular expression localization analysis (ELLA), for modeling the subcellular localization of mRNAs and detecting genes that display spatial variation within cells in high-resolution spatial transcriptomics. ELLA creates a unified cellular coordinate system to anchor diverse cell shapes and morphologies, utilizes a nonhomogeneous Poisson process to model spatial count data, leverages an expression gradient function to characterize subcellular expression patterns, and produces effective control of type I error and high statistical power. We illustrate the benefits of ELLA through comprehensive simulations and applications to four spatial transcriptomics datasets from distinct technologies, where ELLA not only identifies genes with distinct subcellular localization patterns but also associates these patterns with unique mRNA characteristics. Specifically, ELLA shows that genes enriched in the nucleus exhibit an abundance of long noncoding RNAs or protein-coding mRNAs, often characterized by longer gene lengths. Conversely, genes containing signal recognition peptides, encoding ribosomal proteins, or involved in membrane related activities tend to enrich in the cytoplasm or near the cellular membrane. Furthermore, ELLA reveals dynamic subcellular localization patterns during the cell cycle, with certain genes showing decreased nuclear enrichment in the G1 phase while others maintain their enrichment patterns throughout the cell cycle. Overall, ELLA represents a calibrated, powerful, robust, scalable, and versatile tool for modeling subcellular spatial expression variation across diverse high-resolution spatial transcriptomic platforms.
Extracellular phase separation mediates storage and release of thyroglobulin in the thyroid follicular lumen
Authors: Yao Yihan , Erkamp Nadia , Sneideris Tomas , Yang Xiqiao , Scrutton Rob , Schneider Matthias M. , Fischer Charlotte M. , Schoenmakers Erik , Schoenmakers Nadia , Knowles Tuomas P.J. 
Published: September 2024

AbstractThyroid hormones are produced by the thyroid gland and are essential for regulating metabolism, growth and development. Maintenance of circulating thyroid hormone levels within an appropriate range is thus a prerequisite for health.In vivo, this objective is, at least in part, facilitated through an extracellular storage depot of thyroglobulin, the glycoprotein precursor for thyroid hormones, in the thyroid follicular lumen. The molecular basis for how soluble thyroglobulin molecules form such dense depot assemblies remains elusive. Here, we describein vitrobiophysical analysis of thyroglobulin phase behaviour, suggesting that thyroglobulin is prone to undergoing ionic strength-dependent phase separation, leading to the formation of liquid-like condensates. Fluorescence photobleaching measurements further show that these condensates age as a function of time to form reversible gel-like high density storage depots of thyroglobulin. Immunofluorescence experiments on mouse and human thyroid folliclesex vivoreveal that spherical globules of Tg protein dense phase are present in the follicular lumen, consistent with the idea that Tg undergoes phase separation. These findings reveal a molecular mechanism for the last-come-first-served process of thyroglobulin storage and release, suggesting a role for extracellular phase separation in thyroid hormone homeostasis by providing organizational and architectural specificity without requiring membrane-mediated confinement.
Robotic Visible-Light Optical Coherence Tomography Visualizes Segmental Schlemm’s Canal Anatomy and Segmental Pilocarpine Response
Authors: Fang Raymond , Zhang Pengpeng , Kim Daniel , Kweon Junghun , Sun Cheng , Huang Alex S. , Zhang Hao F. 
Published: September 2024

AbstractPurposeTo use robotic visible-light OCT (vis-OCT) to study circumferential segmental Schlemm’s canal (SC) anatomy in mice after topical pilocarpine administration.MethodsAnterior segment imaging was performed using a vis-OCT sample arm attached to a 6-degree-of-freedom robotic arm to maintain normal (perpendicular) laser illumination aimed at SC around the limbus. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. After SC segmentation, SC areas and volumes were measured circumferentially in control- and drug-treated eyes.ResultsCircumferential vis-OCT provided high-resolution imaging of the anterior segment and AHO pathways, including SC. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; p = 0.018). After pilocarpine administration, the iris became flatter, and SC became larger (pilocarpine: 26.8 ± 5.0% vs. control: 8.9 ± 4.6% volume increase; p = 0.030). However, the pilocarpine alteration was segmental as well, with a greater increase observed superior (pilocarpine: 31.6 ± 8.9% vs. control: 1.8 ± 5.7% volume increase; p = 0.023) and nasal (pilocarpine: 41.1 ± 15.3% vs. control: 13.9 ± 4.5% volume increase; p = 0.045).ConclusionHigh-resolution circumferential non-invasive imaging using AS-OCT of AHO pathways is possible in living animals with robotic control. Segmental SC anatomy was seen at baseline and was consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was seen as well. Segmental glaucoma drug response around the circumference of AHO pathways is a novel observation that may explain the variable patient response to glaucoma treatments.
Microbial Degradation of Contaminants of Emerging Concern by Pseudomonas putida in Wastewater Treatment Plants
Authors: Lyu Boyu , Manna Bharat , Zhou Xueyang , Leung Ivanhoe K. H. , Singhal Naresh 
Published: September 2024

ABSTRACTContaminants of Emerging Concern (CECs) are a class of contaminants that are commonly found in urban wastewater treatment plants (WWTP) at low concentrations. These compounds include antibiotic drugs, personal care products, and industrial chemicals, which are widely used in modern society. Although they provide undeniable benefits in our daily lives, their accumulation in the environment poses a significant risk to human health and the ecosystem. Due to the incomplete removal of these compounds by traditional WWTPs, there is a need to understand the interactions between microbes and CECs to develop effective solutions to this environmental challenge.Pseudomonas putidais a bacterium commonly found in water-related habitats, including freshwater streams, forests, and WWTPs. It is known for its ability to degrade various organic compounds, making it a suitable model for understanding the linkages between bacterial enzymes and CECs found in WWTPs. In this study, isolatedPseudomonas putidastrain KT2440 was cultured in lab-scale reactors to mimic the WWTP environment. The degradation of this isolated strain towards different groups of CECs were studied over a 24-hour period using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Mass spectrometry-based quantitative proteomics was also performed at different sampling points to establish a linkage between the enzyme expression profile of this strain and its degradation of CECs via bioinformatics analysis. The results of this study demonstrated thatPseudomonas putidaKT2440 is capable of degrading atrazine, acetamiprid, carbendazim, diclofenac acid, erythromycin, and sulfamethazine at lab scale. At the 20-hour time point, the enzyme expression profile indicated a high protein abundance of various oxidoreductases that could explain the observed CEC degradation.The study’s findings provide important insights into the potential of Pseudomonas putida as a bioremediation agent for CECs in WWTPs. The degradation of CECs byPseudomonas putidaKT2440 is a significant contribution to the bioremediation process, and its enzyme expression profile can serve as a case study for more complex interactions of microbes and CECs in real WWTPs. Furthermore, this study supports the potential ofPseudomonas putidaas a promising strain for various bioremediation applications. Finally, this study’s results can help develop more efficient and effective methods for removing CECs from wastewater, which can contribute to the protection of public health and the environment.
Americans in rural areas are less likely to receive stress management counseling from physicians: a national repeated cross-sectional study of the 2018 and 2019 National Ambulatory Medical Care Survey
Authors: Ira Stephanie Marie , Gillette Chris 
Published: September 2024

AbstractStress is a significant contributor to suicide ideation and attempts. This paper (1) describes the frequency of clinic visits in which physicians record stress management counseling; and (2) identifies visit-, physician-, and patient-related predictors of stress management counseling. We conducted a secondary analysis of the 2018 and 2019 National Ambulatory Medical Care Survey (NAMCS) clinic visit datasets. We identified clinic-, patient-, and physician-related predictors of stress management counseling. All analyses used weighted adjustment to account for the complex survey design. The weighted sample included 1,495,326,615 visits (unweighted (n=14,175) in 2018-2019. Combined, 1.32 per 100 visits (95% CI=0.72-1.92) included stress management counseling. Stress management counseling was less likely to occur when the visit occurred in a rural area (OR=0.22, 95% CI=0.09-0.53), among other characteristics. Stress management counseling rarely occurs during physician office visits in rural areas, despite rural areas suffering disproportionately worse health outcomes than urban areas.
Molecular Diagnosis of Heart Allograft Rejection Using Intra-Graft Targeted Gene Expression Profiling: the heart HistoMX system
Authors: Giarraputo Alessia , Coutance Guillaume , Patel Jignesh K. , Fedrigo Marny , Aubert Olivier , Dagobert Jessy , Mezine Fariza , Robin Blaise , Rouvier Philippe , Varnous Shaida , Van Huyen Jean Paul Duong , Bruneval Patrick , Angelini Annalisa , Kobashigawa Jon , Loupy Alexandre 
Published: September 2024

ABSTRACTBackground and aimsTissular gene expression profiling has the potential to refine the diagnosis of cardiac allograft rejection. Contrary to whole-transcriptome approaches, targeted molecular profiling applicable to formalin-fixed paraffin-embedded (FFPE) endomyocardial biopsies (EMB) can be easily implemented in clinical practice. We aimed to develop and validate the first rejection molecular diagnostic system dedicated to heart transplantation (HTx).MethodsAn international multicenter study was designed, building a deep phenotyped cohort of HTx recipients recruited between 2011 and 2021 at 4 referral centers. Detailed donors, recipients, clinical, immunological, biological, and histological parameters were collected. EMBs were graded according to international working formulations. Tissue gene expression was analyzed on FFPE-EMB using the consensus Banff Human Organ Transplant gene set. Molecular classifiers of antibody-mediated (AMR) and acute cellular rejection (ACR) were built. Discrimination and calibration were assessed in the development and validation sets (NCT06436027).ResultsA total of 591 biopsies were included: 188 AMR (pAMR1(I+): n=51; pAMR1(H+): n=58; pAMR2-3: n=79), 289 ACR (1R n=174; 2-3R n=115) and 114 matched non-rejection cases. Biopsies were split in a derivation (n=476) and a validation set (n=115). AMR top significant transcripts were related to the IFN-gamma inducible pathway, endothelial activation, and monocyte-macrophage recruitment. ACR was characterized by transcripts related to T-cell receptor, CD3 receptor activation, and CD28 signaling. ACR and AMR molecular rejection models were strongly associated with the pathology severity of rejection and accurately identified rejection in the derivation (ROC-AUC: AMR=0.831, ACR:=0.837) and validation sets (ROC-AUC: AMR=0.812; ACR=0.849). Calibration was adequate. The robustness of the molecular classifiers were reinforced by various sensitivity analyzes. An automated report was developed to enhance the reproducibility and clinical applicability of the molecular analysis.ConclusionsIn this study, the first tissue-based rejection molecular diagnostic system applicable to FFPE- EMB and dedicated to heart transplantation rejection was developed and internally validated. This tool has the potential to refine the diagnosis of rejection.