bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reply to Dages, et al. You AIn’t using it right: Artificial intelligence progress in allergy
Authors: Lawless Dylan 
Published: August 2023

AbstractWe present our playful yet serious response to Dages et al.’s letter on AI limitations in allergy, specifically the AI model, ChatGPT. Our lighthearted title, “You AIn’t using it right: Artificial intelligence progress in allergy,” belies our intent to show how AI tools can be used differently to yield reliable, factual information that can enhance the field of medical sciences. We demonstrate by using AI to build a computer program to download and analyse PubMed sources, summarise the content, provide supporting primary evidence, and produce figures to enlighten the reader. We believe that the correct and increasingly automated application of AI can revolutionize its use in medicine, catalyzing its evolution to deliver significant benefits. Therefore, while caution is required, we should not default to dismissing the power of these new tools.
DESIGNING, DEVELOPING AND VALIDATING A SET OF STANDARDIZED PEDIATRIC PICTOGRAMS TO SUPPORT PEDIATRIC-REPORTED GASTRODUODENAL SYMPTOMS
Authors: Humphrey Gayl , Keane Celia , Gharibans Armen , Andrews Christopher N. , Benitez Alain , Mousa Hayat , O’Grady Gregory 
Published: August 2023

ABSTRACTObjectiveTo develop and validate a set of static and animated pediatric gastroduodenal symptom pictograms.MethodsThere were three study phases: 1: Co-creation used experience design methods resulting in ten pediatric gastroduodenal symptom pictograms (static and animation); 2: an online survey to assess acceptability, face and content validity; and 3: a preference study. Phases 2 and 3 compared the novel paediatric pictograms with existing pictograms used with adult patients.ResultsEight children aged 6-15 years (5 Female) participated in Phase 1, 69 children in Phase 2 (median age 13 years: IQR 9-15), and an additional 49 participants were included in Phase 3 (median age 15: IQR 12-17). Face and content validity were higher for the pediatric and animated pictogram sets compared to pre-existing adult pictograms (78% vs. 78% vs. 61%). Participants with worse gastric symptoms (lower PedsQL-GIS score) had superior comprehension of the pediatric pictograms (χ28< .001). The pediatric pictogram set was preferred by all participants over animation and adult (χ22< .001).ConclusionThe co-creation phase resulted in the symptom concept confirmation and design of ten acceptable static and animated gastroduodenal pictograms with high face and content validity when evaluated with children aged 6 to 18. Validity was superior when children reported more problematic symptoms. Therefore, these pictograms could be used in clinical and research practice to enable standardized symptom reporting for children with gastroduodenal disorders.Why is it important▪Diagnosis of gastroduodenal disorders of the gut-brain interaction (DGBI) in pediatrics is difficult as symptoms often overlap.▪Pediatric patients find identifying and distinguishing symptoms difficult.▪Validated gastroduodenal symptom pictograms have been found to help adults accurately report their symptoms and have been used effectively to standardize symptom monitoring, including continuous symptom reporting during investigations.▪There are no validated pediatric gastroduodenal symptom pictograms.What we did▪Co-created a set of ten pediatric gastroduodenal symptom pictograms.▪Undertook a face and content validity study to assess the novel pictograms with 118 pediatric participants with a median PedsQL-GIS score of 86.1 (IQR 68.1-90.0).The Outcome▪Designed a novel set of pictograms with face and content validity that were preferred over other sets, enabling acceptable, simple and validated pediatric patient reporting of their gastroduodenal symptoms.
Cancer and Circulatory Disease Risks for the Largest Solar Particle Events in the Space Age
Authors: Cucinotta Francis A. , Pak Sungmin 
Published: August 2023

AbstractIn this paper we use the NASA Space Cancer Risk (NSCR version 2022) model to predict cancer and circulatory disease risks using energy spectra representing the largest SPE’s observed in the space age. Because tissue dose-rates behind shielding for large SPE’s lead to low dose-rates (<0.2 Gy/h) we consider the integrated risk for several historical periods of high solar activity, including July-November, 1960 events and August-October 1989 events along with the February 1956 and August 1972 events. The galactic cosmic ray (GCR) contribution to risks is considered in predictions. Results for these largest historical events show risk of exposure induced death (REID) are mitigated to < 1.2% with a 95% confidence interval with passive radiation shielding of 20 g/cm2aluminum, while larger amounts would support the application of the ALARA principle. Annual GCR risks are predicted to surpass the risks from large SPEs by ∼30 g/cm2of aluminum shielding.
AI-Enhanced Integration of Genetic and Medical Imaging Data for Risk Assessment of Type 2 Diabetes
Authors: Huang Yi-Jia , Chen Chun-houh , Yang Hsin-Chou 
Published: August 2023

AbstractType 2 diabetes (T2D) is a global public health concern due to its increasing prevalence. Risk assessment and early detection of T2D are vital in improving individuals’ health, reducing the burden on health insurance, and enhancing well-being. This study leverages artificial intelligence (AI), specifically eXtreme Gradient Boosting (XGBoost), to develop predictive models for T2D based on genetic and medical imaging data. The study aims to establish a prediction model and identify high-risk subgroups for T2D within a cohort of 68,911 Taiwan Biobank (TWB) participants. The approach integrates the Polygenic Risk Score (PRS) and Multi-image Risk Score (MRS) with demographic factors and environmental exposures to assess T2D risk. The model’s performance is evaluated using the Area Under the Receiver Operating Curve (AUC). Results demonstrate that genetic information alone is insufficient for accurate T2D prediction (AUC = 0.73), whereas medical imaging data, including abdominal ultrasonography, vertebral artery ultrasonography, bone density scan, and electrocardiography, significantly improves prediction accuracy (AUC = 0.89). The best-performing model integrates genetic, medical imaging, and demographic variables (AUC = 0.94), successfully identifying subgroups at high risk of developing T2D. The study also presents an online risk assessment website for T2D. In summary, this research represents the first integration of genetic and medical imaging data for T2D risk assessment. The genetic-only model outperforms previous genetic prediction studies, and integrating genetic and medical imaging information significantly enhances prediction. By utilizing artificial intelligence to analyze genetic, medical imaging, and demographic factors, this study contributes to early detection and precision health of T2D.
Multiomic ALS signatures highlight sex differences and molecular subclusters and identify the MAPK pathway as therapeutic target
Authors: Caldi Gomes Lucas , Hänzelmann Sonja , Hausmann Fabian , Khatri Robin , Oller Sergio , Parvaz Mojan , Tzeplaeff Laura , Pasetto Laura , Gebelin Marie , Ebbing Melanie , Holzapfel Constantin , Fabrizio Columbro Stefano , Scozzari Serena , Knöferle Johanna , Cordts Isabell , Demleitner Antonia F. , Deschauer Marcus , Dufke Claudia , Sturm Marc , Zhou Qihui , Zelina Pavol , Sudria-Lopez Emma , Haack Tobias B. , Streb Sebastian , Kuzma-Kozakiewicz Magdalena , Edbauer Dieter , Pasterkamp R. Jeroen , Laczko Endre , Rehrauer Hubert , Schlapbach Ralph , Carapito Christine , Bonetto Valentina , Bonn Stefan , Lingor Paul 
Published: August 2023

AbstractAmyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and lacks effective disease-modifying treatments. Here, we performed a multiomic analysis of the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, as well as four transgenic mouse models of C9orf72-, SOD1-, TDP-43-, and FUS-ALS to characterize early and sex-specific disease mechanisms in ALS. Integrated analyses of transcriptomes, (phospho)proteomes, and miRNAomes revealed more pronounced changes in males. We identified transcriptome-based human ALS subclusters driven by the immune response, ECM, mitochondrial respiration, and RNA metabolism. The molecular signatures of human subclusters were reflected in specific mouse models. Individual and integrative multiomics analysis highlighted the mitogen-activated protein kinase pathway as an early disease-relevant mechanism. Its modulation by trametinib in vitro and in vivo validated that mitogen-activated protein kinase kinase 2 is a promising therapeutic target with beneficial effects in females.
Therapeutic inhibition of monocyte recruitment prevents checkpoint inhibitor-induced hepatitis
Authors: Gudd Cathrin LC , Atkinson Stephen R , Mitchell Eoin , Mawhin Marie-Anne , Turajlic Samra , Larkin James , Thursz Mark R , Goldin Robert D , Powell Nick , Antoniades Charalambos G , Woollard Kevin J , Possamai Lucia A , Triantafyllou Evangelos 
Published: August 2023

AbstractCheckpoint inhibitor-induced hepatitis (CPI-hepatitis) is an emerging problem with the widening use of CPIs in cancer immunotherapy. Here, we developed a mouse model to characterise the mechanism of CPI-hepatitis and to therapeutically target key pathways driving this pathology. C57BL/6 wild-type (WT) mice were dosed with TLR9-agonist (TLR9-L) for hepatic priming combined with anti-CTLA-4 plus anti-PD-1 (CPI) or control (PBS) for up to 7 days. Co-administration of CPIs with TLR9-L induced liver pathology closely resembling human disease, with increased infiltration and clustering of granzyme B+perforin+CD8+T cells and CCR2+monocytes, 7 days post treatment. This was accompanied by apoptotic hepatocytes surrounding these clusters and elevated cytokeratin-18 and alanine transaminase plasma levels. Liver RNA sequencing identified key signalling pathways (JAK-STAT, NF-κB) and cytokine/chemokine networks (Ifnγ, Cxcl9, Ccl2/Ccr2) as drivers of CPI-hepatitis. Using this model, we show that CD8+T cells mediate hepatocyte damage in experimental CPI-hepatitis. However, their liver recruitment, clustering, and cytotoxic activity is dependent the presence of CCR2+monocytes. Absence of hepatic monocyte recruitment in Ccr2rfp/rfpmice and CCR2 therapeutic inhibition by cenicriciroc (CVC) in WT mice prevented CPI-hepatitis. In conclusion, using this newly established mouse model, we demonstrate a central role of liver infiltrating CCR2+monocyte interaction with cytotoxic CD8+T cells in the pathogenesis of CPI-hepatitis and highlight novel therapeutic targets.
H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity
Authors: Welsh Robin A. , Song Nianbin , Park Chan-su , Peske J. David , Sadegh-Nasseri Scheherazade 
Published: August 2023

AbstractRegulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of thymic Tregs. We provide evidence that lack of H2-O in the thymic medulla promotes thymic Treg development and leads to an increased peripheral Treg frequency. Single-cell RNA-sequencing (scRNA-seq) analysis of splenic CD4 T cells revealed not only of an enrichment of effector-like Tregs but also of activated CD4 T cells in the absence of H2-O. Our data support two concepts; a) lack of H2-O expression in the thymic medulla creates an environment permissive to Treg development and, b) that loss of H2-O drives increased basal auto-stimulation of CD4 T cells. These findings can help in better understanding of predispositions to autoimmunity and design of therapeutics for treatment of autoimmune diseases.
Genetic evidence for serum amyloid P component as a drug target for treatment of neurodegenerative disorders
Authors: Schmidt A Floriaan , Finan Chris , Chopade Sandesh , Ellmerich Stephan , Rossor Martin N , Hingorani Aroon D , Pepys Mark B 
Published: August 2023

AbstractThe direct causes of neurodegeneration underlying Alzheimer’s disease (AD) and many other dementias, are not known. Here we identify serum amyloid P component (SAP), a constitutive plasma protein normally excluded from the brain, as a potential drug target. After meta-analysis of three genome-wide association studies, comprising 44,288 participants,cis-Mendelian randomization showed that genes responsible for higher plasma SAP values are significantly associated with AD, Lewy body dementia and plasma tau concentration. These genetic findings are consistent with experimental evidence of SAP neurotoxicity and the strong, independent association of neocortex SAP content with dementia at death. Depletion of SAP from the blood and from the brain, as is provided by the safe, well tolerated, experimental drug, miridesap, may therefore contribute to treatment of neurodegeneration.
Expression of FIBCD1 by intestinal epithelial cells alleviates inflammation-driven tumorigenesis in a mouse model of colorectal cancer
Authors: Shahgoli Vahid Khaze , Dubik Magdalena , Pilecki Bartosz , Skallerup Sofie , Schmidt Sandra Gaedt , Detlefsen Sönke , Sorensen Grith L. , Holmskov Uffe , Baradaran Behzad , Moeller Jesper B. 
Published: August 2023

AbstractColorectal cancer (CRC) ranks as the third most prevalent cancer worldwide, highlighting the urgent need to address its development. Inflammation plays a crucial role in augmenting the risk of CRC development and actively contributes to all stages of tumorigenesis. Consequently, targeting early inflammatory responses in the intestinal tract to restore homeostasis holds significant potential for innovative therapeutic strategies against CRC. In this study, we employ transgenic mice that mimic human expression of Fibrinogen C domain containing 1 (FIBCD1), a chitin-binding transmembrane protein primarily present on intestinal epithelial cells (IECs). Previous research has highlighted FIBCD1’s ability to effectively suppress inflammatory responses and foster tissue homeostasis at mucosal barriers. Using the azoxymethane/dextran sodium sulfate mouse model, we demonstrate that FIBCD1 substantially impacts CRC development by significantly reducing intestinal inflammation and suppressing colorectal tumorigenesis. Moreover, we identify a soluble variant of FIBCD1, which is significantly increased in fecal matter during acute inflammation. Together, these findings suggest that FIBCD1 has the potential to be a novel molecular target in the context of colitis-associated colorectal cancer and emerges as an intriguing candidate for future research.
Somatomotor-Visual Resting State Functional Connectivity Increases After Two Years in the UK Biobank Longitudinal Cohort
Authors: Orlichenko Anton , Su Kuan-Jui , Tian Qing , Shen Hui , Deng Hong-Wen , Wang Yu-Ping 
Published: August 2023

ABSTRACTPurposeFunctional magnetic resonance imaging (fMRI) and functional connectivity (FC) have been used to follow aging in both children and older adults. Robust changes have been observed in children, where high connectivity among all brain regions changes to a more modular structure with maturation. In this work, we examine changes in FC in older adults after two years of aging in the UK Biobank longitudinal cohort.ApproachWe process data using the Power264 atlas, then test whether FC changes in the 2,722-subject longitudinal cohort are statistically significant using a Bonferroni-corrected t-test. We also compare the ability of Power264 and UKB-provided, ICA-based FC to determine which of a longitudinal scan pair is older.ResultsWe find a 6.8% average increase in SMT-VIS connectivity from younger to older scan (fromρ= 0.39 toρ= 0.42) that occurs in male, female, older subject (>65 years old), and younger subject (<55 years old) groups. Among all inter-network connections, this average SMT-VIS connectivity is the best predictor of relative scan age, accurately predicting which scan is older 57% of the time. Using the full FC and a training set of 2,000 subjects, one is able to predict which scan is older 82.5% of the time using either the full Power264 FC or the UKB-provided ICA-based FC.ConclusionsWe conclude that SMT-VIS connectivity increases in the longitudinal cohort, while resting state FC increases generally with age in the cross-sectional cohort. However, we consider the possibility of a change in resting state scanner task between UKB longitudinal data acquisitions.
EZH2 synergizes with BRD4-NUT to drive NUT carcinoma growth through silencing of key tumor suppressor genes
Authors: Huang Yeying , Durall R. Taylor , Luong Nhi M. , Hertzler Hans J. , Huang Julianna , Gokhale Prafulla C. , Leeper Brittaney A. , Persky Nicole S. , Root David E. , Anekal Praju V. , Montero Llopis Paula D.L.M. , David Clement N. , Kutok Jeffery L. , Raimondi Alejandra , Saluja Karan , Luo Jia , Zahnow Cynthia A. , Adane Biniam , Stegmaier Kimberly , Hawkins Catherine E. , Ponne Christopher , Le Quan , Shapiro Geoffrey I. , Lemieux Madeleine E. , Eagen Kyle P. , French Christopher A. 
Published: August 2023

ABSTRACTNUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) impede BRD4-NUT’s ability to activate genes and are thus a promising treatment but limited as monotherapy. The role of gene repression in NC is unknown. Here, we demonstrate that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark, and restored expression of multiple tumor suppressor genes while having no effect on key oncogenic BRD4- NUT-regulated genes.CDKN2Awas identified as the only gene amongst all taz-derepressed genes to confer resistance to taz in a CRISPR-Cas9 screen. Combined EZH2 inhibition and BET inhibition synergized to downregulate cell proliferation genes resulting in more pronounced growth arrest and differentiation than either inhibitor alone. In pre-clinical models, combined taz and BETi synergistically blocked growth and prolonged survival of NC-xenografted mice, with all mice cured in one cohort.STATEMENT OF SIGNIFICANCEIdentification of EZH2 as a dependency in NC substantiates the reliance of NC tumor cells on epigenetic dysregulation of functionally opposite, yet highly complementary chromatin regulatory pathways to maintain NC growth. In particular, repression of CDKN2A expression by EZH2 provides a mechanistic rationale for combining EZH2i with BETi for the clinical treatment of NC.
The Enderstruder: An accessible open-source syringe extruder compatible with Ender series 3D printers
Authors: Cordova Domenic J. , Rodriguez Angel A. , Woodward Sabrina C. , Crosby Cody O. 
Published: August 2023

AbstractBioprinting has enabled the precise spatiotemporal deposition of cells and biomaterials, opening new avenues of research in tissue engineering and regenerative medicine. Although several open-source syringe extruder adaptations for bioprinters have been published and adopted by end users, only one has been specifically adapted for the Ender series, an affordable and open-source line of thermoplastic 3D printers. Here, we introduce the Enderstruder, a cost-effective extruder attachment that uses a standard 10 mL BD syringe, positions the stepper motor at the level of the gantry, enhances x-axis stability with a linear rail, and uses the originally included stepper motor, resulting in reduced cost and simplified assembly. Furthermore, we present an iterative process to fine-tune printing profiles for high-viscosity biomaterial inks. To facilitate the implementation of our work by other researchers, we provide fully editable Cura profiles for five commonly used biomaterials. Using these five materials to validate and characterize our design, we employ the Enderstruder to print established calibration patterns and complex shapes. By presenting the Enderstruder and its iterative development process, this study contributes to the growing repository of open-source bioprinting solutions, fostering greater accessibility and affordability for researchers in tissue engineering.Specifications table
In-depth analysis ofKlebsiella aerogenesresistome, virulome and mobilome worldwide
Authors: Morgado Sergio , Fonseca Érica , Freitas Fernanda , Caldart Raquel , Vicente Ana Carolina 
Published: August 2023

AbstractKlebsiella aerogenesis an emergent pathogen associated with outbreaks of carbapenem-resistant strains. To date, studies focusing onK. aerogeneshave been small-scale and/or geographically restricted. Here, we analyzed the epidemiology, resistome, virulome, and mobilome of this species based on 561 genomes, spanning all continents. Furthermore, we sequenced four new strains from Brazil (mostly from the Amazon region). Dozens of STs occur worldwide, but the pandemic clones ST93 and ST4 have prevailed in several countries. Almost all genomes were clinical, however, most of them did not carry ESBL or carbapenemases, instead, they carried chromosomal alterations (omp36,ampD,ampG,ampR) associated with resistance to β-lactams. Integrons were also identified, presenting gene cassettes not yet reported in this species (blaIMP,blaVIM,blaGES). Considering the virulence loci, the yersiniabactin and colibactin operons were found in the ICEKp10 element, which is disseminated in genomes of several STs, as well as an incomplete salmochelin cluster. In contrast, the aerobactin hypervirulence trait was observed only in one ST432 genome. Plasmids were common, mainly from the ColRNAI replicon, with some carrying resistance genes (mcr, blaTEM,blaNDM,blaIMP,blaKPC,blaVIM) and virulence genes (EAST1,senB). Interestingly, plasmids containing the colicin gene occurred in hundreds of genomes of different STs.
Sigmoni: classification of nanopore signal with a compressed pangenome index
Authors: Shivakumar Vikram S. , Ahmed Omar Y. , Kovaka Sam , Zakeri Mohsen , Langmead Ben 
Published: August 2023

AbstractImprovements in nanopore sequencing necessitate efficient classification methods, including pre-filtering and adaptive sampling algorithms that enrich for reads of interest. Signal-based approaches circumvent the computational bottleneck of basecalling. But past methods for signal-based classification do not scale efficiently to large, repetitive references like pangenomes, limiting their utility to partial references or individual genomes. We introduce Sigmoni: a rapid, multiclass classification method based on ther-index that scales to references of hundreds of Gbps. Sigmoni quantizes nanopore signal into a discrete alphabet of picoamp ranges. It performs rapid, approximate matching using matching statistics, classifying reads based on distributions of picoamp matching statistics and co-linearity statistics. Sigmoni is 10-100×faster than previous methods for adaptive sampling in host depletion experiments with improved accuracy, and can query reads against large microbial or human pangenomes.