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| Open AccessAI-enhanced integration of genetic and medical imaging data for risk assessment of Type 2 diabetes
Type 2 diabetes is a global health threat demanding precise healthcare methods. Here, the authors show that their AI-driven risk assessment models, integrating genetic, imaging, and demographic data, achieve high accuracy in identifying high-risk groups, promising advancements in prevention strategies.
- Yi-Jia Huang
- , Chun-houh Chen
- & Hsin-Chou Yang
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| Open AccessSpatial disparities in the mortality burden of the covid-19 pandemic across 569 European regions (2020-2021)
Excess mortality can be used as an indicator of the impacts of the COVID-19 pandemic. Here, the authors estimate excess mortality in 569 European regions in 25 countries for 2020 and 2021 and describe how impacts changed over time.
- Florian Bonnet
- , Pavel Grigoriev
- & Carlo-Giovanni Camarda
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| Open AccessCerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue
After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition with neurological symptoms. Here, the authors show symptom-specific brain microstructure alterations in these patients, providing insights into the underlying pathophysiology.
- Jonas A. Hosp
- , Marco Reisert
- & Alexander Rau
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| Open AccessStimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse
Despite initial treatment with surgical resection, glioblastoma multiforme (GBM) frequently recurs. Here the authors report the design of an immunostimulatory autolysing Salmonella based-nanocapsule delivery system, promoting anti-tumor immune responses and preventing postoperative relapse in preclinical GBM models.
- Yulin Zhang
- , Kaiyan Xi
- & Shilei Ni
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Article
| Open AccessHsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation
Hsc70 (heat shock protein family A member 8) is a cytoplasmic chaperone protein involved in endosomal micro-autophagy and chaperone-mediated autophagy. Here the authors report that Hsc70 promotes lysosomal degradation of PD-L1 and that its overexpression promotes anti-tumor immune responses in preclinical cancer models.
- Xiaoyan Xu
- , Tingxue Xie
- & Hongguang Xia
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| Open AccessEnhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
- Zhenguang Zhang
- , Iain R. L. Kean
- & Nazima Pathan
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Article
| Open AccessEnhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Targeted drug delivery in vivo is a complex challenge, and understanding the characteristics that define the behavior of delivery vehicles in vivo is vital for advancing delivery vehicle design. Here the authors use a library of polymeric delivery vehicles and high-throughput tools to study the structure-function relationships guiding the physiological fate of nanomedicines.
- Alexandra S. Piotrowski-Daspit
- , Laura G. Bracaglia
- & W. Mark Saltzman
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| Open AccessOriginal COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters
Waning immunity and the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness and required vaccine updates. Here, the authors assess how different priming regimens affect the immunogenicity of BA.1 and BA.5 bivalent boosters.
- Luca M. Zaeck
- , Ngoc H. Tan
- & Rory D. de Vries
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Article
| Open AccessMycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine
In this work, authors mechanistically investigate the reduced induction of antimicrobial peptides in Mycobacterium tuberculosis infected macrophages.
- Cheng Peng
- , Yuanna Cheng
- & Lin Wang
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Article
| Open AccessLiver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling
The peroxisomal β-oxidation enzyme ACOX1 increases in liver with obesity, but the physiological significance is unclear. Here, the authors show that liver-specific knockout of Acox1 leads to accumulation of omega-3 VLCFAs that promote metabolic health through activation of GPR120 in adipose tissue.
- Dongliang Lu
- , Anyuan He
- & Irfan J. Lodhi
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Article
| Open AccessGenomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam
Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe community-acquired infection, primarily in Asia. Here, the authors characterise the genetic profile, phylogenetic structure, and plasmid features of hvKp in Vietnam.
- Quynh Nguyen
- , Nguyen Yen Thi Phuong
- & Duy Thanh Pham
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Article
| Open AccessFerritinophagy mediates adaptive resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer
The mechanisms leading to acquired resistance to targeted therapy in cancer are not completely understood. Here, the authors show that ferritinophagy mediates adaptive resistance to Osimertinib, and that combining this EGFR tyrosine kinase inhibitor with copper ionophores improves its therapeutic efficacy in preclinical models of non-small cell lung cancer.
- Hui Wang
- , Qianfan Hu
- & Feng Jiang
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| Open AccessImpacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years
Population mobility is associated with SARS-CoV-2 transmission but its impacts on other respiratory viruses are not well understood. Here, the authors investigate associations between mobile phone-derived mobility metrics and the dynamics of 18 respiratory viruses in Seattle, Washington from 2018 to 2022.
- Amanda C. Perofsky
- , Chelsea L. Hansen
- & Cécile Viboud
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| Open AccessImportance of social inequalities to contact patterns, vaccine uptake, and epidemic dynamics
Contact patterns influence the spread of infectious diseases, but mathematical models of epidemics typically only account for age differences in contacts. Here, the authors investigate the importance of other sociodemographic characteristics in shaping contact patterns and vaccine uptake using survey data from Hungary.
- Adriana Manna
- , Júlia Koltai
- & Márton Karsai
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Article
| Open AccessTDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression
Amyotrophic Lateral Sclerosis is characterized by TDP-43 proteinopathy in the brain. Here, the authors find TDP-43 aggregation might be mediated by the loss of Asparaginase-like 1, an enzyme that degrades detrimental isoaspartates and is downregulated by the endogenous retrovirus HML-2.
- Marta Garcia-Montojo
- , Saeed Fathi
- & Avindra Nath
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| Open AccessBone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes
Bone marrow stromal cells (BMSCs) are known to promote the development of drug resistance. Here, the authors investigate the chromatin remodeling and associated changes in gene expression in the multiple myeloma (MM) cells following their interactions with BMSCs, which are also observed in extramedullary disease (EMD).
- Moritz Binder
- , Raphael E. Szalat
- & Nikhil C. Munshi
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Article
| Open AccessThe vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans
The transition between yeast and hyphae is crucial for the pathogenicity of Candida albicans. Here, Liu et al. show that vacuole fusion is active during hyphal extension and that large vacuoles increase the mechanical forces of hyphae penetrating into organs.
- Yu Liu
- , Ruina Wang
- & Lan Yan
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| Open AccessDynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy
Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.
- Maxime Mistretta
- , Mena Cimino
- & Giulia Manina
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| Open AccessMechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration
The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Here, the authors report a shape-memory, tailorable, self-adaptive and bioactive silk fibroin/magnesium composite scaffold that can quickly match irregular defects by simple trimming and lead to good interface integration.
- Zhinan Mao
- , Xuewei Bi
- & Yufeng Zheng
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| Open AccessSerological evidence of zoonotic filovirus exposure among bushmeat hunters in Guinea
In a serological analysis, Bore et al. utilise serum samples, collected from a cohort of individuals associated with bushmeat hunting and butchering, in the forested region of Guinea, a region close to the epicentre of the 2013–2016 West Africa Ebola virus disease epidemic.
- Joseph Akoi Boré
- , Joseph W. S. Timothy
- & Miles W. Carroll
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| Open AccessE-cardiac patch to sense and repair infarcted myocardium
Infarted myocardium hampers the synchronous electroactivity of the cardiac tissue. Here, the authors showcase a battery-free conductive cardiac patch made of reduced graphene and its therapeutic efficacy for cardiac repair.
- Renjie Qiu
- , Xingying Zhang
- & Leyu Wang
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| Open AccessSevere drought exposure in utero associates to children’s epigenetic age acceleration in a global climate change hot spot
The study suggests a positive association between in utero drought exposure and faster biological aging in children in a global climate change hot spot. Drought experienced during pregnancy may reduce life expectancy.
- Xi Qiao
- , Bilinda Straight
- & Belinda L. Needham
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Article
| Open AccessFOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation
FOXC1 transcription factor plays a role in vascular development, but its mechanism is not well defined. Here, the authors show FOXC1 regulates retinal angiogenesis by promoting CD98 amino acid transporter expression to activate mTOR signalling, and also by promoting blood-retina barrier formation.
- Teena Bhakuni
- , Pieter R. Norden
- & Tsutomu Kume
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| Open AccessIdentifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank
Plasma proteins are a potential diagnostic tool to detect multiple diseases, including cancer. Here, the authors leverage multi-omics data to identify 1,463 proteins associated with 19 common cancers in UK Biobank participants. Reviewer Recognition:
- Keren Papier
- , Joshua R. Atkins
- & Ruth C. Travis
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| Open AccessComparison of intramyocellular lipid metabolism in patients with diabetes and male athletes
Endurance athletes and sedentary type 2 diabetes patients swapped their lifestyle for 8 weeks. Athletes store and utilise saturated fat intensely for performant physical activity, and type 2 diabetes patients reversed their dysmetabolic lipid state after endurance training.
- Alice M. Mezincescu
- , Amelia Rudd
- & Dana Dawson
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Article
| Open AccessThree stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin
Previous studies of the skin have suggested a neutral-to-acidic pH gradient in the outermost layer. Here, the authors perform quantitative intravital pH imaging of the stratum corneum, the outermost epidermal layer, and demonstrate three distinct pH zones - rather than a gradient - with different biological functions.
- Keitaro Fukuda
- , Yoshihiro Ito
- & Masayuki Amagai
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Article
| Open AccessCD5L as a promising biological therapeutic for treating sepsis
Authors explore the utility of CD5L for treating experimental sepsis. CD5L deficiency exacerbates experimental sepsis. Conversely, administration of recombinant CD5L in WT mice augments neutrophil function, enhances bacterial control, and mitigates inflammation, leading to substantial improvements in disease outcomes.
- Liliana Oliveira
- , M. Carolina Silva
- & Alexandre M. Carmo
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Article
| Open AccessIRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis
The endoplasmic reticulum (ER) is a major site of lipid peroxidation during ferroptosis. Here authors show that the ER protein IRE1α determines ferroptosis induction via regulating glutathione synthesis independent of the unfolded protein response.
- Dadi Jiang
- , Youming Guo
- & Albert C. Koong
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Article
| Open AccessCEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials
Cibisatamab is a T-cell bispecific antibody targeting the carcinoembryonic antigen (CEA) on tumor cells and CD3 epsilon chain on T cells. Here the authors report the results of two clinical trials of cibisatamab as monotherapy (NCT02324257) and in combination with atezolizumab (anti-PD-L1; NCT02650713) in patients with CEA-positive solid tumors.
- Neil H. Segal
- , Ignacio Melero
- & Guillem Argilés
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| Open AccessHepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture
Hepatocytes dedifferentiate into progenitor-like cells in culture. Here, authors elucidate the dynamics and mechanisms of hepatocyte dedifferentiation and find an unexpected differentiation potential of hepatocytes into intestinal epithelial cells.
- Shizuka Miura
- , Kenichi Horisawa
- & Atsushi Suzuki
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Article
| Open AccessCell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment
Cell-mediated cytotoxicity observed in untreated SMA patients’ CSF and brain parenchyma. Spatial transcriptomic and multiplex immunohistochemistry linked cytotoxicity near affected motoneurons. Nusinersen treatment showed no impact on this profile.
- I-Na Lu
- , Phyllis Fung-Yi Cheung
- & Gerd Meyer zu Horste
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| Open AccessA burden of proof study on alcohol consumption and ischemic heart disease
Alcohol use is commonplace and ischemic heart disease (IHD) the leading cause of death globally, yet their relationship is unclear. Here we show that study type determines whether research finds alcohol reduces IHD risk or is unrelated, arguing for new approaches to settle this critical debate.
- Sinclair Carr
- , Dana Bryazka
- & Emmanuela Gakidou
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Article
| Open AccessSevere outcomes of malaria in children under time-varying exposure
Severe pediatric malaria remains a concern in many countries. Here, the authors use an individual-based modeling approach to evaluate the relationship between malaria prevalence and incidence of malaria pediatric hospitalizations, and show how unsteady transmission patterns affect hospitalization rates.
- Pablo M. De Salazar
- , Alice Kamau
- & Melissa A. Penny
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| Open AccessDysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation
The impact of obesity on cancer remains insufficiently explored. Here the authors show that in mouse models, dysfunctional adipocytes exhibit low levels of BECN1 which induce YAP/TAZ activity to promote breast and colorectal tumor progression.
- Yaechan Song
- , Heeju Na
- & Han-Woong Lee
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| Open AccessPremature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants
Here, Dzanibe et al show that in utero HIV/ARV exposure sequentially disrupts infant immunologic trajectories, beginning with NK cells that predict vaccine antibody responses and followed by delayed T cell memory maturation linked to skewed TCR clonality.
- Sonwabile Dzanibe
- , Aaron J. Wilk
- & Clive M. Gray
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| Open AccessdsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe
Anaplastic thyroid cancer (ATC) is a particularly aggressive cancer type with limited effective therapeutic options. Here, the authors identify the SUMO E3 ligase PIAS2 as a potential therapeutic target in ATC and mechanistically investigate its role in mitotic spindle and centrosome assembly.
- Joana S. Rodrigues
- , Miguel Chenlo
- & Clara V. Alvarez
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| Open AccessSystematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types
Single-cell sequencing has enabled detailed analyses of the tumour microenvironment (TME). Here, the authors perform an integrative analysis of the TME using single-cell and spatial transcriptomics data from over a thousand tumours across thirty cancer types, identifying interferon-enriched community states predictive of immunotherapeutic responses.
- Junho Kang
- , Jun Hyeong Lee
- & Jong-Eun Park
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| Open AccessSafety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
- Nhân Thị Hồ
- , Steven G. Hughes
- & Xuan-Hung Nguyen
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Article
| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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| Open AccessMammographic density mediates the protective effect of early-life body size on breast cancer risk
Mammographic density is known to be linked to breast cancer risk. Here, the authors use Mendelian randomization to estimate the effects of childhood body size and age at menarche on density phenotypes and breast cancer risk.
- Marina Vabistsevits
- , George Davey Smith
- & Eleanor Sanderson
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Article
| Open AccessRelationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes
Human leucocyte antigens are important in the adaptive immune response. Here, the authors use data from the UK Biobank linked to electronic health records to investigate the association between genetic variation in HLA alleles and antibody responses to SARS-CoV-2 vaccination and breakthrough COVID-19 outcomes.
- Junqing Xie
- , Beatriz Mothe
- & Daniel Prieto Alhambra
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Article
| Open AccessMapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth
Human hepatocytes remain hard to grow in vitro. Here, the authors temporally map the early stages of organoid growth initiated from fetal and adult hepatocytes, leveraging this knowledge to design maturation and improved expansion conditions.
- Delilah Hendriks
- , Benedetta Artegiani
- & Hans Clevers
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Article
| Open AccessRapid and on-site wireless immunoassay of respiratory virus aerosols via hydrogel-modulated resonators
Infectious respiratory viruses have been an everlasting threaten to public health. Here, authors report a wireless immunoassay technology based on immuno-responsive hydrogel-modulated resonant sensors, which facilitate on-site respiratory virus surveillance.
- Xin Li
- , Rujing Sun
- & Qingjun Liu
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Article
| Open AccessA cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys
As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.
- Marlon J. A. de Haan
- , Marleen E. Jacobs
- & Ton J. Rabelink
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Article
| Open AccessA fully autonomous robotic ultrasound system for thyroid scanning
Current thyroid ultrasounds rely heavily on the experience and skills of the sonographer and of the radiologist, and the process is physically and cognitively exhausting. Here, the authors show a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nodules.
- Kang Su
- , Jingwei Liu
- & Peter Xiaoping Liu
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| Open AccessAssessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries
High levels of extended spectrum beta-lactamase (ESBL) and carbapenemase encoding genes were detected in bacterial isolates causing neonatal sepsis in LMICs. Authors assess the in vitro activity of three antibiotics (fosfomycin, flomoxef and amikacin) in combination against ESBL-producing Klebsiella pneumoniae and Escherichia coli isolates.
- Biljana Kakaraskoska Boceska
- , Tuba Vilken
- & Herman Goossens
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Article
| Open AccessThe pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis
Cardiovascular events are the main cause of mortality in patients with metabolic dysfunctionassociated steatohepatitis (MASH). Here, the authors show that lanifibranor improves cardiometabolic health - insulin sensitivity, lipid and glucose metabolism, systemic inflammation and hepatic steatosis.
- Michael P. Cooreman
- , Javed Butler
- & Sven M. Francque
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| Open AccessVOLTA: an enVironment-aware cOntrastive ceLl represenTation leArning for histopathology
While machine learning platforms can improve the assessment of Hematoxylin & Eosin (H&E) stained-tumour tissue images, current models typically require manual cell-type annotations in training. Here, the authors develop VOLTA, a self-supervised machine learning framework to improve cell representation learning in H&E images based on the cells environment
- Ramin Nakhli
- , Katherine Rich
- & Ali Bashashati
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| Open AccessHerpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase
Encephalitis is a rare and severe complication of Herpes Simplex type 1 infection. Here, Bibert et al describe a genetic variant in a 2-year-old affected child that impairs interferon production in neuronal cells and enhances viral replication.
- Stéphanie Bibert
- , Mathieu Quinodoz
- & Pierre-Yves Bochud