tbuckley/cabot-search huggingface dataset:
Modulatory effects of CNNM4 on Protein-L-Isoaspartyl-O-Methyltransferase repair function during Alcohol-Induced hepatic damage
Authors: Irene González-Recio, Naroa Goikoetxea-Usandizaga, Claudia M. Rejano-Gordillo, Carolina Conter, Rubén Rodríguez Agudo, Marina Serrano-Maciá, L Estefanía Zapata-Pavas, Patricia Peña-Sanfélix, Mikel Azkargorta, Félix Elortza, José María Herranz, Álex Guillamon Thiery, Armando Raúl Guerra-Ruiz, Ramiro Jover, Unai Galicia-Garcia, César Martín, Ute Schaeper, Teresa C. Delgado, Irene Díaz-Moreno, Antonio Díaz Quintana, Daniela Buccella, Rubén Nogueiras, JosepMaria Argemi, Matías A. Ávila, Jordi Gratacós-Ginès, Paula Iruzubieta, Elisa Pose, Ramón Bataller, Javier Crespo, Luis Alfonso Martínez-Cruz, Ma Luz Martínez-Chantar
Journal: Hepatology (2024)

Background and Aims: Alcohol-related liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence and liver transplantation. Chronic alcohol consumption has been linked to magnesium (Mg 2+ ) deficiency, which can influence the liver disease progression. The mechanisms underlying Mg 2+ homeostasis dysregulation in ALD remain elusive. This study aimed to investigate the role of the Mg 2+ transporter Cyclin M4 (CNNM4) in ALD by analyzing its expression patterns in ALD patients and preclinical animal models. Approach and Results: In this study, CNNM4 is upregulated in the liver of both ALD patients and animal models. CNNM4 overexpression triggers Mg²⁺ homeostasis dysregulation, linked to ALD progression. We propose a novel therapeutic approach for ALD treatment using N-acetylgalactosamine (GalNAc) silencing RNA (siRNA) technology to specifically modulate Cnnm4 expression in the liver, improving mitochondrial function and alleviating ER stress. Notably, silencing Cnnm4 restores protein isoaspartyl methyltransferase (PCMT1) activity, essential for repairing ethanol-induced protein damage. Enhancing mitochondrial activity through Cnnm4-dependent mechanisms increases SAMe levels, crucial for PCMT1 function, highlighting the interconnected roles of mitochondrial health and protein homeostasis in ALD treatment. Conclusions: These findings shed light on the dysregulation of Mg 2+ homeostasis in ALD, providing a promising therapeutic approach targeting CNNM4. GalNAc si Cnnm4 therapy boost the repair processes of ethanol damaged proteins through the upregulation of PCMT1 activity.
High <scp>I</scp>g<scp>G</scp> Anti‐<scp>I</scp>g<scp>E</scp> Autoantibodies Prevent Early Omalizumab Response in Chronic Spontaneous Urticaria
Authors: Yusuke Niwa, Koremasa Hayama, Shota Toyoshima, Keisuke Shimizu, Maho Tagui, Mana Ito, Tomomi Sakamoto, Tadashi Terui, Hideki Fujita, Yoshimichi Okayama
Journal: Allergy (2024)
Endotyping in Chronic Rhinosinusitis—An <scp>EAACI</scp> Task Force Report
Authors: Sanna Toppila‐Salmi, Sietze Reitsma, Valérie Hox, Simon Gane, Ibon Eguiluz‐Gracia, Mohamed Shamji, Juan Maza‐Solano, Benjamin Jääskeläinen, Risto Väärä, Maria M. Escribese, Adam Chaker, Aspasia Karavelia, Michael Rudenko, Philippe Gevaert, Ludger Klimek
Journal: Allergy (2024)

ABSTRACT Chronic rhinosinusitis (CRS) is a clinical syndrome defined by typical sinonasal symptoms persisting for at least 12 weeks. CRS is divided into two distinct phenotypes, CRS with nasal polyps (CRSwNP) and without (CRSsNP). The aim of the review is to provide an update on the current knowledge in CRS endotypes. The prevailing hypothesis regarding the pathogenesis of CRS suggests that dysfunctional interactions between the host and environmental stressors at the mucosal surface drive the diverse inflammatory mechanisms. Genetic and epigenetic variations in the mucosal immune system are believed to play a significant role in the pathomechanisms of CRS. Various environmental agents (such as microbes and irritants) have been implicated in CRS. In a healthy state, the sinonasal mucosa acts as a barrier, modulating environmental stimulation and mounting appropriate immune responses against pathogens with minimal tissue damage. Different endotypes may exist based on the specific mechanistic pathways driving the chronic tissue inflammation of CRS. There is a need to understand endotypes in order to better predict, diagnose, and treat CRS. This literature review provides an update on the role of the endotypes in CRS and the limitations of endotyping CRS in clinical practice. Understanding of the pathogenesis and optimal management of CRS has progressed significantly in the last decades; however, there still are several unmet needs in endotype research.
Real‐World Finetuning of Biomarkers in Severe Asthma: Longitudinal Latent Class Analysis From the Italian Registry on Severe Asthma (<scp>IRSA</scp>)
Authors: M. Beatrice Bilò, Matteo Martini, Leonardo Antonicelli, Fausto de Michele, Adriano Vaghi, Antonino Musarra, Claudio Micheletto
Journal: Allergy (2024)
Allergen‐Specific Immunotherapy and Trained Immunity
Authors: Leticia Martín‐Cruz, Oscar Palomares
Journal: Allergy (2024)

ABSTRACT The high prevalence of allergic diseases reached over the last years is attributed to the complex interplay of genetic factors, lifestyle changes, and environmental exposome. Allergen‐specific immunotherapy (AIT) is the single therapeutic strategy for allergic diseases with the potential capacity to modify the course of the disease. Our knowledge of the mechanisms involved in allergy and successful AIT has significantly improved. Recent findings indicate that long‐term allergen tolerance upon AIT discontinuation not only relies on the generation of proper adaptive immune responses by the generation of allergen‐specific regulatory T and B cells enabling the induction of different isotypes of blocking antibodies but also relies on the restoration of proper innate immune responses. Trained immunity (TRIM) is the process by which innate immune cells acquire memory by mechanisms depending on metabolic and epigenetic reprogramming, thus conferring the host with increased broad protection against infection. This concept was initially explored for infectious diseases, as well as for vaccination against infections, but compelling experimental evidence suggests that TRIM might also play a role in allergy and AIT. Hyperinflammatory innate immune responses in early life, likely due to TRIM maladaptations, lead to aberrant type 2 inflammation‐enhancing allergy. However, exposure to farming environments and specific microbes prevents recurrent infections and allergy development, likely due to mechanisms partially depending on TRIM. TRIM‐based vaccines and next‐generation AIT vaccines inducing metabolic and epigenetic reprogramming in innate immune cells and their precursors have shown protective antiallergic effects. A better understanding of the factors involved in early‐life TRIM mechanisms in the context of allergy and the identification and characterization of novel tolerance inducers might well enable the design of alternative TRIM‐based allergen vaccines for allergic diseases.
The Circular RNA circSKA3 Binds Integrin β1 to Induce Invadopodium Formation Enhancing Breast Cancer Invasion
Authors: William W. Du, Weining Yang, Xiangmin Li, Ling Fang, Nan Wu, Feiya Li, Yu Chen, Qihan He, Elizabeth Liu, Zhenguo Yang, Faryal Mehwish Awan, Mingyao Liu, Burton B. Yang
Journal: Molecular Therapy (2024)
Evoking stable and precise tactile sensations via multi-electrode intracortical microstimulation of the somatosensory cortex
Authors: Charles M. Greenspon, Giacomo Valle, Natalya D. Shelchkova, Taylor G. Hobbs, Ceci Verbaarschot, Thierri Callier, Ev I. Berger-Wolf, Elizaveta V. Okorokova, Brianna C. Hutchison, Efe Dogruoz, Anton R. Sobinov, Patrick M. Jordan, Jeffrey M. Weiss, Emily E. Fitzgerald, Dillan Prasad, Ashley Van Driesche, Qinpu He, Fang Liu, Robert F. Kirsch, Jonathan P. Miller, Ray C. Lee, David Satzer, Jorge Gonzalez-Martinez, Peter C. Warnke, Abidemi B. Ajiboye, Emily L. Graczyk, Michael L. Boninger, Jennifer L. Collinger, John E. Downey, Lee E. Miller, Nicholas G. Hatsopoulos, Robert A. Gaunt, Sliman J. Bensmaia
Journal: Nature Biomedical Engineering (2024)

Tactile feedback from brain-controlled bionic hands can be partially restored via intracortical microstimulation (ICMS) of the primary somatosensory cortex. In ICMS, the location of percepts depends on the electrode's location and the percept intensity depends on the stimulation frequency and amplitude. Sensors on a bionic hand can thus be linked to somatotopically appropriate electrodes, and the contact force of each sensor can be used to determine the amplitude of a stimulus. Here we report a systematic investigation of the localization and intensity of ICMS-evoked percepts in three participants with cervical spinal cord injury. A retrospective analysis of projected fields showed that they were typically composed of a focal hotspot with diffuse borders, arrayed somatotopically in keeping with their underlying receptive fields and stable throughout the duration of the study. When testing the participants' ability to rapidly localize a single ICMS presentation, individual electrodes typically evoked only weak sensations, making object localization and discrimination difficult. However, overlapping projected fields from multiple electrodes produced more localizable and intense sensations and allowed for a more precise use of a bionic hand. An analysis of the localization and intensity of intracortical microstimulation in three participants with cervical spinal cord injury shows that overlapping projected fields from multiple electrodes produce sensations that are more easily localizable.
Geographical variation in lung function: Results from the multicentric cross-sectional BOLD study
Authors: Peter G.J. Burney, James Potts, Ben Knox-Brown, Gregory Erhabor, Hamid Hacene Cherkaski, Kevin Mortimer, Mahesh Padukudru Anand, David M Mannino, Joao Cardoso, Rana Ahmed, Asma Elsony, Cristina Barbara, Rune Nielsen, Eric Bateman, Stefanni Nonna M Paraguas, Li Cher Loh, Abdul Rashid, Emiel FM Wouters, Frits ME Franssen, Hermínia Brites Dias, Thorarinn Gislason, Mohammed Al Ghobain, Mohammed El Biaze, Dhiraj Agarwal, Sanjay Juvekar, Fatima Rodrigues, Daniel O Obaseki, Parvaiz A. Koul, Imed Harrabi, Asaad A Nafees, Terence Seemungal, Christer Janson, William M Vollmer, Andre FS Amaral, A Sonia Buist
Journal: Pulmonology (2024)

Spirometry is used to determine what is "unusual" lung function compared with what is "usual" for healthy non-smokers. This study aimed to investigate regional variation in the forced vital capacity (FVC) and in the forced expiratory volume in one second to FVC ratio (FEV1/FVC) using cross-sectional data from all 41 sites of the multinational Burden of Obstructive Lung Disease study. Participants (5,368 men; 9,649 women), aged ≥40 years, had performed spirometry, had never smoked and reported no respiratory symptoms or diagnoses. To identify regions with similar FVC, we conducted a principal component analysis (PCA) on FVC with age, age2 and height2, separately for men and women. We regressed FVC against age, age2 and height2, and FEV1/FVC against age and height2, for each sex and site, stratified by region. Mean age was 54 years (both sexes), and mean height was 1.69 m (men) and 1.61 m (women). The PCA suggested four regions: 1) Europe and richer countries; 2) the Near East; 3) Africa; and 4) the Far East. For the FVC, there was little variation in the coefficients for age, or age2, but considerable variation in the constant (men: 2.97 L in the Far East to 4.08 L in Europe; women: 2.44 L in the Far East to 3.24 L in Europe) and the coefficient for height2. Regional differences in the constant and coefficients for FEV1/FVC were minimal (<1%). The relation of FVC with age, sex and height varies across and within regions. The same is not true for the FEV1/FVC ratio.
Deep learning biomarker of chronometric and biological ischemic stroke lesion age from unenhanced CT
Authors: Adam Marcus, Grant Mair, Liang Chen, Charles Hallett, Claudia Ghezzou Cuervas-Mons, Dylan Roi, Daniel Rueckert, Paul Bentley
Journal: npj Digital Medicine (2024)

Abstract Estimating progression of acute ischemic brain lesions – or biological lesion age - holds huge practical importance for hyperacute stroke management. The current best method for determining lesion age from non-contrast computerised tomography (NCCT), measures Relative Intensity (RI), termed Net Water Uptake (NWU). We optimised lesion age estimation from NCCT using a convolutional neural network – radiomics (CNN-R) model trained upon chronometric lesion age (Onset Time to Scan: OTS), while validating against chronometric and biological lesion age in external datasets ( N = 1945). Coefficients of determination (R 2 ) for OTS prediction, using CNN-R, and RI models were 0.58 and 0.32 respectively; while CNN-R estimated OTS showed stronger associations with ischemic core:penumbra ratio, than RI and chronometric, OTS (ρ 2 = 0.37, 0.19, 0.11); and with early lesion expansion (regression coefficients &gt;2x for CNN-R versus others) (all comparisons: p &lt; 0.05). Concluding, deep-learning analytics of NCCT lesions is approximately twice as accurate as NWU for estimating chronometric and biological lesion ages.
Cold acclimation with shivering improves metabolic health in adults with overweight or obesity
Authors: Adam J. Sellers, Sten M. M. van Beek, Dzhansel Hashim, Rosalie Baak, Hannah Pallubinsky, Esther Moonen-Kornips, Gert Schaart, Anne Gemmink, Johanna A. Jörgensen, Tineke van de Weijer, Eric Kalkhoven, Guido J. Hooiveld, Sander Kersten, Matthijs K. C. Hesselink, Patrick Schrauwen, Joris Hoeks, Wouter D. van Marken Lichtenbelt
Journal: Nature Metabolism (2024)
Persistence of OXA-48-producing ST-22 Citrobacter freundii in patients and the hospital environment, Paris, France, 2016 to 2022
Authors: Sarah Jolivet, Jeanne Couturier, Killian Le Neindre, Muriel Ehmig, Laurent Dortet, Cécile Emeraud, Frédéric Barbut
Journal: Eurosurveillance (2024)

In 2016–2019, hospital A’s haematology ward experienced an outbreak of OXA-48-producing ST-22 Citrobacter freundii strains, with toilets identified as source of transmission. Between 2020 and 2022, 28 strains of OXA-48-producing ST-22 C. freundii were isolated on other wards. This study aimed to determine whether all OXA-48-producing ST-22 C. freundii strains belonged to the same clone and to investigate the persistence of this clone using whole genome sequencing. OXA-48-producing ST-22 C. freundii strains collected from patients (n = 33) and from the hospital environment (n = 20) of seven wards were sequenced using Illumina technology and clonal relationships were determined using single nucleotide polymorphism (SNP). Phylogenetic analyses were performed on 53 strains from hospital A and on 240 epidemiologically unrelated carbapenem-resistant ST-22 C. freundii isolated from elsewhere in France. SNP analysis suggested long-lasting persistence of the same clone for more than 6 years. Phylogenetic analysis showed that 52 of 53 strains isolated in hospital A belonged to the same cluster and were different from the 240 epidemiologically unrelated C. freundii ST-22. Our data suggest that this clone can persist in hospital environments for years, representing a risk for hospital-acquired infections and outbreaks. Reservoir management is essential to prevent further transmission.
Ultrasmall High‐Entropy‐Alloy Nanozyme Catalyzed In Vivo ROS and NO Scavenging for Anti‐Inflammatory Therapy
Authors: Daeeun Choi, Yeonju Boo, Seonhye Park, Liangliang Xu, Seongbeen Kim, Seung Yeop Yi, Sangmin Lee, Ruopeng Wu, Won Jong Kim, Jinwoo Lee
Journal: Advanced Healthcare Materials (2024)

Abstract High‐entropy alloy (HEA) nanoparticles possess finely tunable and multifunctional catalytic activity due to their extremely diverse adsorption sites. Their unique properties enable HEA nanoparticles to mimic the complex interactions of the redox homeostasis system, which is composed of cascade and multiple enzymatic reactions. The application of HEAs in mimicking complex enzymatic systems remains relatively unexplored, despite the importance of regulating biological redox reactions. Here, it is reported that ultra‐small (&lt;10 nm in a diameter) HEA nanozymes consisting of five platinum‐group metals with tunable morphologies from planar to dendritic structures are synthesized. The synthesized HEA nanozymes exhibited higher peroxidase‐like activity compared to monometallic platinum‐group nanoparticles. Additionally, HEA nanoparticles effectively mimicked RONS‐regulation metabolism in cascade reactions involving superoxide dismutase and catalase, as well as in multiple reactions including HORAC and NO scavenging. As a result, the HEA nanozyme exhibited superior anti‐inflammatory efficacy both in vitro and in vivo. The findings underscore the effectiveness of the high‐entropy alloy structure in restoring in vivo enzymatic systems through intrinsic activity enhancements and cascade reaction mechanisms.
Reasons for difficulties in isolating the causative organism during food-borne outbreak investigations using STEC as a model pathogen: a systematic review, 2000 to 2019
Authors: Christina Anthony, Karen Pearson, Rebecca Callaby, Lesley Allison, Claire Jenkins, Alison Smith-Palmer, Marianne James
Journal: Eurosurveillance (2024)

Introduction Food-borne disease outbreak investigations use epidemiological, microbiological and food chain evidence to identify the implicated food and inform risk management actions. Aims We used Shiga toxin-producing Escherichia coli (STEC) as a model pathogen to investigate the success of outbreak strain isolation from food or environmental samples during outbreak investigations, and examined the factors influencing the chance of isolation. Methods We searched for reports of food-borne STEC outbreak investigations worldwide in peer-reviewed and grey literature in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results We found a total of 223 outbreaks suitable for inclusion. Food and/or environmental samples were available for testing in 137 investigations, and the outbreak strain was isolated in 94 (42%) of investigations. We found no significant effect of STEC serovar or size of outbreak on likelihood of successful outbreak strain isolation. Isolation success ranged across different implicated commodities from 86% for beef-related outbreaks to 50% for salads and leafy greens. In 20% of outbreaks with samples available for testing, an additional STEC strain was isolated alongside the outbreak strain and in 6.6%, only an alternative STEC strain was isolated. Risk management action was taken on epidemiological evidence alone in 21 incidents. Conclusion The principal reasons why the outbreak strain was not isolated were lack of sample availability and methodological issues concerned with laboratory isolation. We recommend strategies that could improve the likelihood of isolation including the rapid collection of samples based on epidemiological intelligence.
Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions
Authors: Selina M. Vattathil, Ekaterina S. Gerasimov, Se Min Canon, Adriana Lori, Sarah Sze Min Tan, Paul J. Kim, Yue Liu, Eric C. Lai, David A. Bennett, Thomas S. Wingo, Aliza P. Wingo
Journal: Nature Aging (2024)

Abstract MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex samples of 604 older adult donors of European ancestry. Here we show that nearly half (224 of 470) of the analyzed miRNAs have associated miR-QTLs, many of which fall in regulatory regions such as brain promoters and enhancers. We also demonstrate that intragenic miRNAs often have genetic regulation independent from their host genes. Furthermore, by integrating our findings with 16 genome-wide association studies of psychiatric and neurodegenerative disorders, we identified miRNAs that likely contribute to bipolar disorder, depression, schizophrenia and Parkinson’s disease. These findings advance understanding of the genetic regulation of miRNAs and their role in brain health and disease.
Macrolide-resistant Bordetella pertussis strain identified during an ongoing epidemic, Finland, January to October 2024
Authors: Milja Miettinen, Alex-Mikael Barkoff, Aino Nyqvist, Carita Savolainen-Kopra, Jenni Antikainen, Jussi Mertsola, Lauri Ivaska, Qiushui He
Journal: Eurosurveillance (2024)

Since April 2024, a pertussis epidemic has been ongoing in Finland with 2,215 notified cases by end October. Of them, 30.1% (n = 667) were aged 10–14 years. Of the 462 Bordetella pertussis isolates characterised, one was macrolide-resistant (minimum inhibitory concentration (MIC) of erythromycin, azithromycin and clarithromycin &gt; 256 μg/mL). The resistant isolate was serotype FIM2, vaccine antigen pertactin-deficient and harboured ptxP3 allele. The emergence of macrolide-resistant B. pertussis in Europe is worrisome and its rapid identification is important.
A “Janus” Zwitterionic Hydrogel Patch for Tissue Repair and Prevention of Post‐Operative Adhesions
Authors: Jing Zhang, Xinxin Luo, Jiaqi Liu, Minmin Wu, Jie Feng, Jia Zhou
Journal: Advanced Healthcare Materials (2024)

Abstract Anti‐peritoneal adhesions (PA) are very important after abdominal surgery for that PA often leads to other medical problems and imposes a huge financial burden on the national healthcare system. In this work, a “Janus” zwitterionic hydrogel patch where one side can adhere firmly to the tissue, while the other side has anti‐fouling properties and has little interaction with the surrounding tissue has been developed. The “Janus” hydrogel patch is prepared by in situ formation of a bonding polymer layer poly(acrylic‐co‐N‐hydroxysuccinimide acrylate) on one side of zwitterionic hydrogel. The mechanical, swelling, adhesion, biodegradability and biocompatibility tests are performed to study the function of “Janus” hydrogel patch to prevent wound adhesion and rapid repair. It is found that the adhesive side of the hydrogel patch has stable adhesion to tissues, avoiding the slippage faced by many commercial anti‐adhesion gels in the body. The other zwitterionic side can resist proteins and fibroblasts and prevent external interactions or adhesion with other tissues. This convenient and effective method provides a new idea for the design of postoperative anti‐adhesion materials and broadens the application of hydrogels in the biomedical field.
Vaccinating against the absent: Risks of the B/Yamagata strain in the live attenuated vaccine
Authors: Parvaiz A Koul
Journal: Eurosurveillance (2024)

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