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| Open AccessGestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota
Here, Marcado-Evans et al show that gestational diabetes enhances group B Streptococcus infection through altering host-microbe dynamics, disrupting maternal immunity, and perturbing the vaginal microbiota in a murine pregnancy model.
- Vicki Mercado-Evans
- , Marlyd E. Mejia
- & Kathryn A. Patras
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Article
| Open AccessLocal structural preferences in shaping tau amyloid polymorphism
In this work, using a combination of Cryo-EM, in-cell experiments and biophysical analysis, the authors decoded the aggregation propensity of tau, revealing 5 central hot spots in its primary sequence and identify PAM4 as short segment that determines both the structure, as well as the cellular propagation of tau aggregates extracted from Alzheimer’s disease, corticobasal degeneration, and progressive supranuclear palsy patients.
- Nikolaos Louros
- , Martin Wilkinson
- & Joost Schymkowitz
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Article
| Open AccessProgrammed microalgae-gel promotes chronic wound healing in diabetes
The treatment of infected diabetic wounds faces obstacles of bacterial infection, hypoxia, hyperexpression of reactive oxygen species, and inflammation. Here, the authors address these issues by developing a programmed treatment strategy that utilizes live Haematococcus to promote healing of diabetic wounds in a comprehensive manner.
- Yong Kang
- , Lingling Xu
- & Xiaoyuan Ji
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Article
| Open AccessPhosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma
Upregulation of GLI1 of has previously been reported in sonic hedgehog (SHH) driven medulloblastoma and basal cell carcinoma (BCC). Here, the authors find that SHH-inactivation of p38 results in stabilization of the transcription factor GLI1 via dephosphorylation at Ser937, resulting in expression of SHH genes and presenting a potential therapy strategy for medulloblastoma and BCC.
- Ling-Hui Zeng
- , Chao Tang
- & Jirong Wang
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Article
| Open AccessRisk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population
The factors influencing risk of reinfection with SARS-CoV-2 are poorly understood. Here, the authors use data from the UK COVID-19 Infection Survey, a community based longitudinal study, to assess characteristics of ~45,000 reinfections compared to initial infections.
- Jia Wei
- , Nicole Stoesser
- & Chris Cunningham
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Article
| Open AccessEarly onset diagnosis in Alzheimer’s disease patients via amyloid-β oligomers-sensing probe in cerebrospinal fluid
In this work, the authors characterize a small molecule fluorescent probe pioneering early diagnosis of Alzheimer’s disease through identification of amyloid-β oligomers in patients’ cerebrospinal fluid, demonstrating potential for clinical application.
- Jusung An
- , Kyeonghwan Kim
- & Jong Seung Kim
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Article
| Open AccessIdentification of potential aggregation hotspots on Aβ42 fibrils blocked by the anti-amyloid chaperone-like BRICHOS domain
This study identifies potential aggregation hotspots on the fibril surface of Alzheimer’s disease associated Aβ42 fibrils, which are blocked by the anti-amyloid chaperone-like domain BRICHOS.
- Rakesh Kumar
- , Tanguy Le Marchand
- & Axel Abelein
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Article
| Open AccessCongenital heart disease detection by pediatric electrocardiogram based deep learning integrated with human concepts
Congenital heart disease is life threatening, and its screening is complex and costly. Here, authors use AI to detect the disease based on pediatric electrocardiogram, suggesting superior performance over cardiologists.
- Jintai Chen
- , Shuai Huang
- & Huiying Liang
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Article
| Open AccessMaternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study
Pertussis immunisation for pregnant women has been introduced to protect newborns, but immunological evidence suggests that this lessens subsequent infant immune response to vaccination. Here, the authors assess the epidemiological impacts of both consequences of maternal immunisation on infant infection.
- Michael Briga
- , Elizabeth Goult
- & Matthieu Domenech de Cellès
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Article
| Open AccessDimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.
- Peter Sandercock
- , Janet Darbyshire
- & Martin J. Landray
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Comment
| Open AccessAfrican leadership is critical in responding to public health threats
The African continent demonstrated decisive leadership throughout its response to the COVID-19 pandemic, leveraging lessons learned from previous outbreaks and acting quickly to limit the impact of the SARS-CoV-2 virus. We propose a framework to build on these successes that calls for greater collaboration between African leaders, and greater inclusion of African voices in the global health ecosystem.
- Nicaise Ndembi
- , Aggrey Aluso
- & Jean Kaseya
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Article
| Open AccessA nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota
Here, the authors develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, to treat Helicobacter pylori.
- Tao Liu
- , Shuang Chai
- & Lihua Yang
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Article
| Open AccessPRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury
Excessive inflammatory responses contribute to severe malaria. Here, Du et al, show that the protein tyrosine phosphatase PRL2 contributes to neutrophil activation and extracellular trap release in an experimental model of severe malaria.
- Xinyue Du
- , Baiyang Ren
- & Zhaojun Wang
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Article
| Open AccessSexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation
Vitiligo is an autoimmune condition that results in skin depigmentation due to melanocyte loss, but the root causes are not well understood. Here they identify sexual dimorphism in melanocyte stem cells behavior arising from distinct skin inflammatory responses, and propose Prostaglandin E2 as a potential therapy for depigmentation conditions.
- Luye An
- , Dahihm Kim
- & Andrew C. White
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Article
| Open AccessEngineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model
Miniature gene editing tools are highly desired for efficient in vivo delivery and disease treatment. Here, the authors reported engineering hypercompact TnpB-ωRNA for robust gene editing with minimal off-target effect in cultured cells and use it to rescue fatal genetic liver disease in a tyrosinaemia mouse model.
- Zhifang Li
- , Ruochen Guo
- & Chunlong Xu
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Article
| Open AccessStructural and functional insights into the lipid regulation of human anion exchanger 2
Anion exchanger 2 (AE2), a widely expressed Cl- /HCO3 - exchanger, participates in the regulation of intracellular pH. Here, the authors present the structures of AE2 and uncover the regulatory mechanism of PIP2.
- Weiqi Zhang
- , Dian Ding
- & Yuxin Yin
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Article
| Open AccessInvestigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing
Non-malarial febrile illnesses have a range of potential aetiologies which are difficult to diagnose and therefore treat. Here, the authors investigate the causes of acute febrile illness in a peri-urban area of Senegal with low malaria incidence using untargeted and targeted sequencing methods.
- Zoë C. Levine
- , Aita Sene
- & Katherine J. Siddle
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Article
| Open AccessA drug-free cardiovascular stent functionalized with tailored collagen supports in-situ healing of vascular tissues
The efficacy of drug-eluting stents remains limited due to delayed reendothelialization, impaired intimal remodeling, and potentially increased late restenosis. Here the authors propose a one-produces-multi stent coating, a drug-free strategy that supports in situ healing of vascular tissues, as demonstrated in rabbit and porcine models.
- Haoshuang Wu
- , Li Yang
- & Yunbing Wang
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Article
| Open AccessWNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease
Fibroblast heterogeneity is a recognized feature in chronic kidney disease, and although fibrosis is integrant to the pathology, it is lesser known which of the fibroblast populations contribute. Here authors describe a population of proinflammatory fibroblasts, which are found in close proximity to macrophages and may facilitate their recruitment and acquisition of a FOLR2+, pathogenic phenotype.
- Camille Cohen
- , Rana Mhaidly
- & Fatima Mechta-Grigoriou
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Article
| Open AccessRespiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study
Unusually high rates of respiratory distress were observed in infants following in utero exposure to SARS-CoV-2. Here the authors find, in a longitudinal cohort of infants born to persons infected with SARS-CoV-2 during pregnancy, that maternal vaccination is associated with a lower odds of infant respiratory distress.
- Olivia M. Man
- , Tamiris Azamor
- & Karin Nielsen-Saines
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Article
| Open AccessAn IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life
Neutrophils play critical roles in response to infection, and the limit of available neutrophils in neonates and young infants can impact responses to infections, including sepsis. Here the authors identify that the IL-10/DEL-1 axis is involved in emergency granulopoiesis in neonates and suggest a link to sepsis survival in early life.
- Eleni Vergadi
- , Ourania Kolliniati
- & Christos Tsatsanis
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Article
| Open AccessShifting patterns of dengue three years after Zika virus emergence in Brazil
Dengue virus circulation was unusually low in Brazil in 2015-2018 following the emergence of Zika virus, but subsequently resurged causing large outbreaks with a lower mean age of infection. Here, the authors use mathematical modelling to investigate the links between dengue dynamics and prior Zika infection.
- Francesco Pinotti
- , Marta Giovanetti
- & José Lourenço
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Article
| Open AccessLeukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice
Cancer cachexia is a systemic syndrome characterized by dramatic weight loss and decline in adipose tissue and skeletal muscle mass. Here, the authors show that overexpression of leukemia inhibitory factor (LIF), a secreted cytokine, suppresses de novo lipogenesis and induces cachexia in mice.
- Xue Yang
- , Jianming Wang
- & Wenwei Hu
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Article
| Open AccessEndothelial leakiness elicited by amyloid protein aggregation
This study reports endothelial leakiness in vitro, in silico and in vivo, where adherens junctions are disrupted by their exposure to the anionic oligomers and seeds of Alzheimer’s amyloid beta, preceding proinflammatory and pro-oxidative events.
- Yuhuan Li
- , Nengyi Ni
- & Pu Chun Ke
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Article
| Open AccessGenetic architecture distinguishes tinnitus from hearing loss
The genetic basis of tinnitus and how it relates to hearing loss genetics is unknown. In a large GWAS for tinnitus, the authors discover tinnitus’ distinct genetic architecture from hearing loss and its correlation with a spectrum of psychiatric disorders.
- Royce E. Clifford
- , Adam X. Maihofer
- & Caroline M. Nievergelt
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Article
| Open AccessDeterminants of epidemic size and the impacts of lulls in seasonal influenza virus circulation
Seasonal influenza levels were unusually low when non-pharmaceutical interventions for COVID-19 were in place. Here, the authors analyse serological and epidemiological evidence for the hypothesis that such lulls in influenza transmission lead to reduced immunity and therefore larger epidemics in subsequent seasons.
- Simon P. J. de Jong
- , Zandra C. Felix Garza
- & Colin A. Russell
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Article
| Open AccessAltered DNA methylation within DNMT3A, AHRR, LTA/TNF loci mediates the effect of smoking on inflammatory bowel disease
Cigarette smoking is an established risk factor for inflammatory bowel disease. The authors suggest that smoking may affect the risk of Crohn’s disease and ulcerative colitis by modulating the DNA methylation status of the DNMT3A, LTA/TNF, and AHRR region, respectively.
- Han Zhang
- , Rahul Kalla
- & Xue Li
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Article
| Open AccessRisk of COVID-19 death in adults who received booster COVID-19 vaccinations in England
Ward et al. utilise electronic health records to identify groups of adults (who had received a second booster dose of a COVID-19 vaccine) at elevated risk of COVID-19 death.
- Isobel L. Ward
- , Chris Robertson
- & Vahé Nafilyan
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Article
| Open AccessHHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant
Lower respiratory tract disease is a common complication after allogeneic hematopoietic cell transplant (HCT), but underlying reasons remain unclear. Here the authors show that HHV-6B detection in the lungs of allogeneic HCT recipients is associated with increased risk for death and distinct host gene expression profiles, implicating HHV-6B as a pulmonary pathogen in these patients.
- Joshua A. Hill
- , Yeon Joo Lee
- & Michael Boeckh
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Article
| Open AccessLarge scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development
The pathobiology of heart failure (HF) is incompletely understood. The authors identify 37 circulating proteins and 5 protein modules associated with HF risk, with several demonstrating causal effects on HF, risk factors, or cardiac dysfunction by Mendelian randomization analysis.
- Amil M. Shah
- , Peder L. Myhre
- & Bing Yu
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Article
| Open AccessSystematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples
SARS-CoV-2 coinfections may lead to recombination events which could be important in the emergence of new variants. Here, the authors develop an automated bioinformatics pipeline to identify coinfections in genomic data and test it on >2 million publicly available raw read data sets collected globally.
- Orsolya Anna Pipek
- , Anna Medgyes-Horváth
- & István Csabai
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Article
| Open AccessPersonalising intravenous to oral antibiotic switch decision making through fair interpretable machine learning
The decision to switch patients from intravenous to oral antibiotic therapy is important for the individual and wider society. Here, authors show a machine learning model using routine clinical data can predict when a patient could switch.
- William J. Bolton
- , Richard Wilson
- & Timothy M. Rawson
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Article
| Open AccessGlobal emergence of a hypervirulent carbapenem-resistant Escherichia coli ST410 clone
In this work, the authors identified a hypervirulent carbapenem-resistant Escherichia coli ST410 clone which carries a high pathogenicity island and an O-antigen gene cluster. The findings highlight the ongoing evolution of ST410 towards increased resistance and virulence.
- Xiaoliang Ba
- , Yingyi Guo
- & Chao Zhuo
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Article
| Open AccessDiabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila
The mechanisms underlying diabetic neuropathy remain elusive. Here, the authors identify that UCHL1 deubiquitinase positively regulates insulin signaling and its loss leads to axonal degeneration of sensory neurons.
- Daewon Lee
- , Eunju Yoon
- & Jongkyeong Chung
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Article
| Open AccessROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease
Steroid-refractory acute graft-versus-host disease (aGVHD) is associated with a low one-year survival rate. Here, the authors show that ROCK1 is upregulated in leukocytes from patients with steroid-refractory aGVHD and that ROCK1/2 inhibition reduces the severity of aGVHD in mice by interfering with activation of multiple immune cell types.
- Kristina Maas-Bauer
- , Anna-Verena Stell
- & Robert Zeiser
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Article
| Open AccessDisparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents
Hantaan virus is carried and transmitted by rodents and results in asymptomatic infection, yet transmission to humans’ results in symptomatic disease and development of hemorrhagic fever with renal syndrome. Here the authors explore the disparate effects in myeloid cells from mice and humans.
- Hongwei Ma
- , Yongheng Yang
- & Fanglin Zhang
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Article
| Open AccessLevels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression
Complement factor H-related 4 protein (FHR-4) has been implicated in the pathophysiology of age-related macular degeneration (AMD). Here, in contrast, the authors find that levels of FHR-4 in plasma or ocular tissue do not appear to influence susceptibility to AMD or its course of progression, questioning whether modulation of FHR-4 is likely to be an effective therapeutic strategy.
- M. A. Zouache
- , B. T. Richards
- & G. S. Hageman
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Article
| Open AccessUpregulated pexophagy limits the capacity of selective autophagy
An accumulation of one substrate of selective autophagy can lead to autophagic degradation deficiencies. Here, the authors show that a pathogenic increase in a single autophagy pathway restricts another by consuming the cell’s autophagy capacity.
- Kyla Germain
- , Raphaella W. L. So
- & Peter K. Kim
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Article
| Open AccessIntegrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma
The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis.
- Andrew R. Hamel
- , Wenjun Yan
- & Ayellet V. Segrè
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Article
| Open AccessNon-Faradaic optoelectrodes for safe electrical neuromodulation
Nanoscale optoelectrodes hold the potential to optically stimulate individual neuron. Here, the authors form nanoscale capacitive optoelectrodes by incorporating zinc porphyrin into nanorods, coated by TiO2, a design that allows for far-field optical modulation of neurons with efficiency and negligible side effects.
- Jian Chen
- , Yanyan Liu
- & Wenbo Bu
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Article
| Open AccessGasdermin E dictates inflammatory responses by controlling the mode of neutrophil death
Apoptotic and lytic cell death pathways are both utilised in the removal of damaged cells; however, the downstream inflammatory outcomes widely vary according to the chosen pathway. Here authors show that in mice with genetic deletion of Gasdermin E specifically in neutrophils, these cells undergo apoptosis rather than pyroptotic cell death upon senescence, with consequential attenuation of reactive inflammatory responses.
- Fengxia Ma
- , Laxman Ghimire
- & Hongbo R. Luo
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Article
| Open AccessMultiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum
The parasite Cryptosporidium has a reduced genome and is dependent on glycolysis for energy production. Here, Xu et al demonstrate that multiple pathways and glucose transporters exist in this organism which are essential for growth and facilitate energy acquisition and utilization.
- Rui Xu
- , Wandy L. Beatty
- & L. David Sibley
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Article
| Open AccessVariants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation
A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis.
- Andrea Accogli
- , Saurabh Shakya
- & Christopher J. Westlake
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Article
| Open AccessEstimating the heritability of SARS-CoV-2 susceptibility and COVID-19 severity
How our genes and environment determine our vulnerability to SARS-CoV-2 infection and the severity of COVID19 remains uncertain. Here, the authors find that as the pandemic progressed the relative importance of genetic variation increased, highlighting the dynamic nature of heritability amidst changing public policies and vaccination rates.
- Kathleen LaRow Brown
- , Vijendra Ramlall
- & Nicholas P. Tatonetti
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Article
| Open AccessGene-SGAN: discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering
Many diseases can display distinct brain imaging phenotypes across individuals, potentially reflecting disease subtypes. However, biological interpretability is limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Here, the authors describe a deep-learning method that links imaging phenotypes with genetic factors, thereby conferring genetic correlations to the disease subtypes.
- Zhijian Yang
- , Junhao Wen
- & Christos Davatzikos
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Article
| Open AccessRadiomic tractometry reveals tract-specific imaging biomarkers in white matter
Diffusion MRI is used for tract-specific microstructural analysis of the white matter. Here, the authors introduce radiomic tractometry (RadTract), enhancing tractometry with radiomics-based imaging biomarkers for improved predictive modelling.
- Peter Neher
- , Dusan Hirjak
- & Klaus Maier-Hein
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Article
| Open Access15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β
Specialised pro-resolving lipid mediators can reduce inflammatory responses and may be active in lymphedema. Here the authors show that in a mouse model 15-LO derived lipid mediators are reduced during inflammation and that a lack of the 15-LO producing enzyme aggravated disease and addition of 15-LO enzyme or Treg cells reduced disease.
- A. Zamora
- , M. Nougué
- & B. Garmy-Susini
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Article
| Open AccessCullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity
Asthma may be exacerbated by respiratory viral infection, but the cellular and molecular mechanisms are still unclear. Here the authors show, using mouse models of asthma with influenza infection, that asthma-induced cullin5 in alveolar macrophages suppresses IFN-β production to promote neutrophilic inflammation but dampens antiviral immunity.
- Haibo Zhang
- , Keke Xue
- & Lei Sun
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Article
| Open AccessMuscle abnormalities worsen after post-exertional malaise in long COVID
In this longitudinal, case-controlled, cohort design study, authors show that post-exertional malaise is associated with severe exercise-induced myopathy, local and systemic metabolic disturbances and infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID.
- Brent Appelman
- , Braeden T. Charlton
- & Rob C. I. Wüst
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