bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental obesity predisposes to exacerbated metabolic and inflammatory disturbances in childhood obesity within the framework of an altered profile of trace elements
Authors: González-Domínguez Álvaro , Jurado-Sumariva Lucía , Domínguez-Riscart Jesús , Saez-Benito Ana , González-Domínguez Raúl 
Published: January 2024

Abstract
Background
Family history of obesity is known to increase the odds of developing childhood obesity in the offspring, but its influence in underlying molecular complications remains unexplored.

Subjects/Methods
Here, we investigated a population-based cohort comprising children with obesity, with and without parental obesity (PO+, N = 20; PO−, N = 29), and lean healthy children as controls (N = 30), from whom plasma and erythrocyte samples were collected to characterize their multi-elemental profile, inflammatory status, as well as carbohydrate and lipid metabolisms.

Results
We found parental obesity to be associated with unhealthier outcomes in children, as reflected in increased blood insulin levels and reduced insulin sensitivity, unfavorable lipid profile, and pro-inflammatory milieu. This was accompanied by moderate alterations in the content of trace elements, including increased copper-to-zinc ratios and iron deficiency in circulation, as well as metal accumulation within erythrocytes.

Conclusions
Therefore, we hypothesize that family history of obesity could be an important risk factor in modulating the characteristic multi-elemental alterations behind childhood obesity, which in turn could predispose to boost related comorbidities and metabolic complications.
One thousand patients with essential thrombocythemia: the Mayo Clinic experience
Authors: Gangat Naseema , Karrar Omer , Al-Kali Aref , Begna Kebede H. , Elliott Michelle A. , Wolanskyj-Spinner Alexandra P. , Pardanani Animesh , Hanson Curtis A. , Ketterling Rhett P. , Tefferi Ayalew 
Published: January 2024

AbstractWe describe 1000 patients with essential thrombocythemia seen at the Mayo Clinic between 1967 and 2023: median age 58 years (18–90), females 63%, JAK2/CALR/MPL-mutated 62%/27%/3%, triple-negative (TN) 8%, extreme thrombocytosis (ExT; platelets ≥1000 × 109/L) 26%, leukocytosis (leukocyte count >11 × 109/L) 20%, and abnormal karyotype 6%. JAK2-mutated patients were older (median 71 years), and CALR mutated (52 years), and TN (50 years) younger (p < 0.01). Female gender clustered with TN (73%) and JAK2 (69%) vs. CALR/MPL (49%/47%) mutations (p < 0.01). ExT clustered with CALR (type-2 more than type-1) and TN and leukocytosis with JAK2 mutation (p < 0.01). In multivariable analysis, risk factors for overall survival were older age (p < 0.01), male gender (HR 1.8), absolute neutrophil count (ANC) ≥ 8 × 109/L (HR 1.6), absolute lymphocyte count (ALC) < 1.7 × 109/L (HR 1.5), hypertension (HR 1.7), and arterial thrombosis history (HR 1.7); for leukemia-free survival, ExT (HR 2.3) and abnormal karyotype (HR 3.1); for myelofibrosis-free survival, ANC ≥ 8 × 109/L (HR 2.3) and MPL mutation (HR 3.9); for arterial thrombosis-free survival, age ≥60 years (HR 1.9), male gender (HR 1.6), arterial thrombosis history (HR 1.7), hypertension (HR 1.7), and JAK2 mutation (HR 1.8); for venous thrombosis-free survival, male gender (HR 1.8) and venous thrombosis history (HR 3.0). Associations between ExT and leukemic transformation and between ANC and fibrotic progression were limited to JAK2-mutated cases. Aspirin therapy appeared to mitigate both arterial (HR 0.4) and venous (HR 0.4) thrombosis risk. HR-based risk models delineated patients with median survivals ranging from 10 years to not reached and 20-year leukemia/myelofibrosis incidences from 3%/21% to 12.8%/49%. The current study provides both novel and confirmatory observations of essential thrombocythemia.
The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway
Authors: Tang Ming , Yin Shasha , Zeng Hongliang , Huang Ao , Huang Yujia , Hu Zhiyi , Shah Ab Rauf , Zhang Shuyong , Li Haisen , Chen Guofang 
Published: January 2024

AbstractEndometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.
SARS-CoV-2 immunity in animal models
Authors: Chen Zhao , Yuan Yaochang , Hu Qingtao , Zhu Airu , Chen Fenghua , Li Shu , Guan Xin , Lv Chao , Tang Tian , He Yiyun , Cheng Jinling , Zheng Jie , Hu Xiaoyu , Zhao Jingxian , Zhao Jincun , Sun Jing 
Published: January 2024

AbstractThe COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals. These complications encompass symptoms such as coughing, respiratory distress, fever, infectious shock, acute respiratory distress syndrome (ARDS), and even multiple-organ failure. Animal models serve as crucial tools for investigating pathogenic mechanisms, immune responses, immune escape mechanisms, antiviral drug development, and vaccines against SARS-CoV-2. Currently, various animal models for SARS-CoV-2 infection, such as nonhuman primates (NHPs), ferrets, hamsters, and many different mouse models, have been developed. Each model possesses distinctive features and applications. In this review, we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection, as well as the corresponding immune responses and applications of these models. A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients. Finally, we highlighted the current gaps in related research between animal model studies and clinical investigations, underscoring lingering scientific questions that demand further clarification.
Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging
Authors: Paudel Bidur , Jeong Si-Yeon , Martinez Carolina Pena , Rickman Alexis , Haluck-Kangas Ashley , Bartom Elizabeth T. , Fredriksen Kristina , Affaneh Amira , Kessler John A. , Mazzulli Joseph R. , Murmann Andrea E. , Rogalski Emily , Geula Changiz , Ferreira Adriana , Heckmann Bradlee L. , Green Douglas R. , Sadleir Katherine R. , Vassar Robert , Peter Marcus E. 
Published: January 2024

AbstractAlzheimer’s disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aβ42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of “SuperAgers”, humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aβ42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aβ42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.
Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity
Authors: Lin Quy Xiao Xuan , Rajagopalan Deepa , Gamage Akshamal M. , Tan Le Min , Venkatesh Prasanna Nori , Chan Wharton O. Y. , Kumar Dilip , Agrawal Ragini , Chen Yao , Fong Siew-Wai , Singh Amit , Sun Louisa J. , Tan Seow-Yen , Chai Louis Yi Ann , Somani Jyoti , Lee Bernett , Renia Laurent , Ng Lisa F P , Ramanathan Kollengode , Wang Lin-Fa , Young Barnaby , Lye David , Singhal Amit , Prabhakar Shyam 
Published: January 2024

AbstractDue to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy.
Modelling six sustainable development transformations in Australia and their accelerators, impediments, enablers, and interlinkages
Authors: Allen Cameron , Biddulph Annabel , Wiedmann Thomas , Pedercini Matteo , Malekpour Shirin 
Published: January 2024

AbstractThere is an urgent need to accelerate progress on the Sustainable Development Goals (SDGs) and recent research has identified six critical transformations. It is important to demonstrate how these transformations could be practically accelerated in a national context and what their combined effects would be. Here we bridge national systems modelling with transformation storylines to provide an analysis of a Six Transformations Pathway for Australia. We explore important policies to accelerate progress, synergies and trade-offs, and conditions that determine policy success. We find that implementing policy packages to accelerate each transformation would boost performance on the SDGs by 2030 (+23% above the baseline). Policymakers can maximize transformation synergies through investments in energy decarbonization, resilience, social protection, and sustainable food systems, while managing trade-offs for income and employment. To overcome resistance to transformations, ambitious policy action will need to be underpinned by technological, social, and political enabling conditions.
Rapid-charging aluminium-sulfur batteries operated at 85 °C with a quaternary molten salt electrolyte
Authors: Meng Jiashen , Hong Xufeng , Xiao Zhitong , Xu Linhan , Zhu Lujun , Jia Yongfeng , Liu Fang , Mai Liqiang , Pang Quanquan 
Published: January 2024

AbstractMolten salt aluminum-sulfur batteries are based exclusively on resourcefully sustainable materials, and are promising for large-scale energy storage owed to their high-rate capability and moderate energy density; but the operating temperature is still high, prohibiting their applications. Here we report a rapid-charging aluminium-sulfur battery operated at a sub-water-boiling temperature of 85 °C with a tamed quaternary molten salt electrolyte. The quaternary alkali chloroaluminate melt – possessing abundant electrochemically active high-order Al-Cl clusters and yet exhibiting a low melting point – facilitates fast Al3+ desolvation. A nitrogen-functionalized porous carbon further mediates the sulfur reaction, enabling the battery with rapid-charging capability and excellent cycling stability with 85.4% capacity retention over 1400 cycles at a charging rate of 1 C. Importantly, we demonstrate that the asymmetric sulfur reaction mechanism that involves formation of polysulfide intermediates, as revealed by operando X-ray absorption spectroscopy, accounts for the high reaction kinetics at such temperature wherein the thermal management can be greatly simplified by using water as the heating media.
PROST: quantitative identification of spatially variable genes and domain detection in spatial transcriptomics
Authors: Liang Yuchen , Shi Guowei , Cai Runlin , Yuan Yuchen , Xie Ziying , Yu Long , Huang Yingjian , Shi Qian , Wang Lizhe , Li Jun , Tang Zhonghui 
Published: January 2024

AbstractComputational methods have been proposed to leverage spatially resolved transcriptomic data, pinpointing genes with spatial expression patterns and delineating tissue domains. However, existing approaches fall short in uniformly quantifying spatially variable genes (SVGs). Moreover, from a methodological viewpoint, while SVGs are naturally associated with depicting spatial domains, they are technically dissociated in most methods. Here, we present a framework (PROST) for the quantitative recognition of spatial transcriptomic patterns, consisting of (i) quantitatively characterizing spatial variations in gene expression patterns through the PROST Index; and (ii) unsupervised clustering of spatial domains via a self-attention mechanism. We demonstrate that PROST performs superior SVG identification and domain segmentation with various spatial resolutions, from multicellular to cellular levels. Importantly, PROST Index can be applied to prioritize spatial expression variations, facilitating the exploration of biological insights. Together, our study provides a flexible and robust framework for analyzing diverse spatial transcriptomic data.
A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types
Authors: Swygart David , Yu Wan-Qing , Takeuchi Shunsuke , Wong Rachel O. L. , Schwartz Gregory W. 
Published: January 2024

AbstractIn early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that heterogeneity in the level of surround suppression occurs subcellularly at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing.
Molecular switching in transcription through splicing and proline-isomerization regulates stress responses in plants
Authors: Theisen Frederik Friis , Prestel Andreas , Elkjær Steffie , Leurs Yannick H. A. , Morffy Nicholas , Strader Lucia C. , O’Shea Charlotte , Teilum Kaare , Kragelund Birthe B. , Skriver Karen 
Published: January 2024

AbstractThe Arabidopsis thaliana DREB2A transcription factor interacts with the negative regulator RCD1 and the ACID domain of subunit 25 of the transcriptional co-regulator mediator (Med25) to integrate stress signals for gene expression, with elusive molecular interplay. Using biophysical and structural analyses together with high-throughput screening, we reveal a bivalent binding switch in DREB2A containing an ACID-binding motif (ABS) and the known RCD1-binding motif (RIM). The RIM is lacking in a stress-induced DREB2A splice variant with retained transcriptional activity. ABS and RIM bind to separate sites on Med25-ACID, and NMR analyses show a structurally heterogeneous complex deriving from a DREB2A-ABS proline residue populating cis- and trans-isomers with remote impact on the RIM. The cis-isomer stabilizes an α-helix, while the trans-isomer may introduce energetic frustration facilitating rapid exchange between activators and repressors. Thus, DREB2A uses a post-transcriptionally and post-translationally modulated switch for transcriptional regulation.
Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics
Authors: Zeng Liuting , Yu Ganpeng , Yang Kailin , He Qi , Hao Wensa , Xiang Wang , Long Zhiyong , Chen Hua , Tang Xiaojun , Sun Lingyun 
Published: January 2024

AbstractTo explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-β signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.
DiaNet v2 deep learning based method for diabetes diagnosis using retinal images
Authors: Al-Absi Hamada R. H. , Pai Anant , Naeem Usman , Mohamed Fatma Kassem , Arya Saket , Sbeit Rami Abu , Bashir Mohammed , El Shafei Maha Mohammed , El Hajj Nady , Alam Tanvir 
Published: January 2024

AbstractDiabetes mellitus (DM) is a prevalent chronic metabolic disorder linked to increased morbidity and mortality. With a significant portion of cases remaining undiagnosed, particularly in the Middle East North Africa (MENA) region, more accurate and accessible diagnostic methods are essential. Current diagnostic tests like fasting plasma glucose (FPG), oral glucose tolerance tests (OGTT), random plasma glucose (RPG), and hemoglobin A1c (HbA1c) have limitations, leading to misclassifications and discomfort for patients. The aim of this study is to enhance diabetes diagnosis accuracy by developing an improved predictive model using retinal images from the Qatari population, addressing the limitations of current diagnostic methods. This study explores an alternative approach involving retinal images, building upon the DiaNet model, the first deep learning model for diabetes detection based solely on retinal images. The newly proposed DiaNet v2 model is developed using a large dataset from Qatar Biobank (QBB) and Hamad Medical Corporation (HMC) covering wide range of pathologies in the the retinal images. Utilizing the most extensive collection of retinal images from the 5545 participants (2540 diabetic patients and 3005 control), DiaNet v2 is developed for diabetes diagnosis. DiaNet v2 achieves an impressive accuracy of over 92%, 93% sensitivity, and 91% specificity in distinguishing diabetic patients from the control group. Given the high prevalence of diabetes and the limitations of existing diagnostic methods in clinical setup, this study proposes an innovative solution. By leveraging a comprehensive retinal image dataset and applying advanced deep learning techniques, DiaNet v2 demonstrates a remarkable accuracy in diabetes diagnosis. This approach has the potential to revolutionize diabetes detection, providing a more accessible, non-invasive and accurate method for early intervention and treatment planning, particularly in regions with high diabetes rates like MENA.
Exploration of photoprotective and antibiotic activity of wild Polypodiaceae ferns from Costa Rica
Authors: Salazar-Chacón Yaclyn , Gutierrez-Bolaños Maria José , Padilla-Cordero Jimena , Vidaurre-Rodriguez Camilo , Carvajal-Miranda Yendry , Rojas-Alvarado Alexander , Rodríguez-Rodríguez Jorengeth Abad , Rodríguez-Rodríguez Gerardo , Álvarez-Valverde Víctor , Jiménez-Bonilla Pablo 
Published: January 2024

AbstractSkin disorders affect millions of people all over the world. There are limited options to treat dermal illnesses such as vitiligo, psoriasis, and atopic dermatitis (eczema). Central American ferns are a potential source of bioactive metabolites against those diseases. Currently, Polypodium leucotomos Poir. is the only one being commercially utilized for this purpose. In this work, we evaluated the concentration of the skin bioactive compounds: quinic and chlorogenic acid, in the extract of 20 wild ferns from Costa Rica. We also evaluated the antimicrobial capabilities of the crude extracts of wild ferns and the sun protection factor (SPF) of the extracts. We found 19 out of 20 have either an important concentration of the compounds mentioned above or antimicrobial properties. Also, most samples result in higher SPF than P. aureum’s rhizome. We also have studied the fern acclimatization, at different shading conditions, finding a significant influence of the culturing conditions on metabolite production. After acclimatization. So far, we demonstrate that various ferns included in this study are a potential source of treatments for skin conditions.