EBioMedicine最新文献

{"title":"Patterns of the within-host evolution of human norovirus in immunocompromised individuals and implications for treatment.","authors":"Ray W Izquierdo-Lara, Nele Villabruna, Dennis A Hesselink, Claudia M E Schapendonk, Sol Ribó Pons, David Nieuwenhuijse, Jenny I J Meier, Ian Goodfellow, Virgil A S H Dalm, Pieter L A Fraaij, Jeroen J A van Kampen, Marion P G Koopmans, Miranda de Graaf","doi":"10.1016/j.ebiom.2024.105391","DOIUrl":"10.1016/j.ebiom.2024.105391","url":null,"abstract":"<p><strong>Background: </strong>Currently, there is no licensed treatment for chronic norovirus infections, but the use of intra-duodenally-delivered immunoglobulins is promising; nevertheless, varying results have limited their wide use. Little is known about the relationship between norovirus genetic diversity and treatment efficacy.</p><p><strong>Methods: </strong>We analyzed the norovirus within-host diversity and evolution in a cohort of 20 immunocompromised individuals using next-generation sequencing (NGS) and clone-based sequencing of the capsid (VP1) gene. Representative VP1s were expressed and their glycan receptor binding affinity and antigenicity were evaluated.</p><p><strong>Findings: </strong>The P2 domain, within the VP1, accumulated up to 30-fold more non-synonymous mutations than other genomic regions. Intra-host virus populations in these patients tended to evolve into divergent lineages that were often antigenically distinct. Several of these viruses were widely resistant to binding-blocking antibodies in immunoglobulin preparations. Notably, for one patient, a single amino-acid substitution in the P2 domain resulted in an immune-escape phenotype, and it was likely the main contributor to treatment failure. Furthermore, we found evidence for transmission of late-stage viruses between two immunocompromised individuals.</p><p><strong>Interpretation: </strong>The findings demonstrated that within-host noroviruses in chronic infections tend to evolve into antigenically distinct subpopulations. This antigenic evolution was likely caused by the remaining low immunity levels exerted by immunocompromised individuals, possibly undermining antiviral treatment. Our observations provide insights into norovirus (within-host) evolution and treatment.</p><p><strong>Funding: </strong>Erasmus MC grant mRACE, the European Union's Horizon 2020 research and innovation program under grant agreement No. 874735 (VEO), and the NWO STEVIN award (Koopmans).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105391"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of temperature on non-typhoidal Salmonella and Campylobacter infections: an updated systematic review and meta-analysis of epidemiological evidence.","authors":"Yohannes Tefera Damtew, Michael Tong, Blesson Mathew Varghese, Olga Anikeeva, Alana Hansen, Keith Dear, Tim Driscoll, Ying Zhang, Tony Capon, Peng Bi","doi":"10.1016/j.ebiom.2024.105393","DOIUrl":"10.1016/j.ebiom.2024.105393","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;As temperatures rise, the transmission and incidence of enteric infections such as those caused by Salmonella and Campylobacter increase. This study aimed to review and synthesise the available evidence on the effects of exposure to ambient temperatures on non-typhoidal Salmonella and Campylobacter infections.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic search was conducted for peer-reviewed epidemiological studies published between January 1990 and March 2024, in PubMed, Scopus, Embase, and Web of Science databases. Original observational studies using ecological time-series, case-crossover or case-series study designs reporting the association between ambient temperature and non-typhoidal Salmonella and Campylobacter infections in the general population were included. A random-effects meta-analysis was performed to pool the relative risks (RRs) per 1 °C temperature increase, and further meta regression, and subgroup analyses by climate zone, temperature metrics, temporal resolution, lag period, and continent were conducted. The Navigation Guide systematic review methodology framework was used to assess the quality and strength of evidence. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Out of 3472 results, 44 studies were included in this systematic review encompassing over one million cases each of Salmonella and Campylobacter infections. Geographically, the 44 studies covered 27 countries across five continents and most of the studies were from high income countries. The meta-analysis incorporated 23 Salmonella studies (65 effect estimates) and 15 Campylobacter studies (24 effect estimates). For each 1 °C rise in temperature, the risk of non-typhoidal Salmonella and Campylobacter infections increased by 5% (RR: 1.05, 95% CI: 1.04-1.06), and 5% (RR: 1.05, 95% CI: 1.04-1.07%), respectively, with varying risks across different climate zones. The overall evidence was evaluated as being of \"high\" quality, and the strength of the evidence was determined to be \"sufficient\" for both infections.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;These findings emphasise the relationship between temperature and the incidence of Salmonella and Campylobacter infections. It is crucial to exercise caution when generalising these findings, given the limited number of studies conducted in low and middle-income countries. Nevertheless, the results demonstrate the importance of implementing focused interventions and adaptive measures, such as the establishment of localised early warning systems and preventive strategies that account for climatic fluctuations. Furthermore, our research emphasises the ongoing need for surveillance and research efforts to monitor and understand the changing dynamics of temperature-related enteric infections in the context of climate change.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;Australian Research Council Discovery Pro","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105393"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterising developmental dynamics of adult epigenetic clock sites.","authors":"Rosa H Mulder, Alexander Neumann, Janine F Felix, Matthew Suderman, Charlotte A M Cecil","doi":"10.1016/j.ebiom.2024.105425","DOIUrl":"10.1016/j.ebiom.2024.105425","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation (DNAm), an epigenetic mechanism that regulates gene activity in response to genetic and environmental influences, changes as we age. DNAm at specific sites on the genome can be used to calculate 'epigenetic clocks', which are powerful biomarkers of age, as well as of ageing. However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimise healthy ageing well before the onset of age-related conditions.</p><p><strong>Methods: </strong>We leveraged results from two longitudinal population-based cohorts (N = 5019 samples from 2348 individuals) to characterise trajectories of adult clock sites from birth to early adulthood. To explore what factors may drive early individual differences at these clock sites, we also tested for enrichment of genetic factors and prenatal exposures based on existing epigenome-wide association meta-analyses.</p><p><strong>Findings: </strong>We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic influences and prenatal environmental exposures, including prenatal smoking, diet and maternal physical health conditions.</p><p><strong>Interpretation: </strong>These results suggests that age(ing)-related epigenetic processes might originate-and differ between individuals-already very early in development. Understanding what drives these differences may in future help us to devise better strategies to promote healthy ageing.</p><p><strong>Funding: </strong>This research was conducted while C.A.M.C. was a Hevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience Research. Full personal funding details, as well as cohort funding details, can be found in the Acknowledgements.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105425"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Big insights from small samples: uncovering the potential of EUS-guided FNAs in pancreatic cancer through predictive genomics and transcriptomics.","authors":"Melissa Zhao, Anirban Maitra, Jonathan A Nowak","doi":"10.1016/j.ebiom.2024.105380","DOIUrl":"10.1016/j.ebiom.2024.105380","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105380"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a two-year follow-up of the prospective clinical trial COVAXID.","authors":"Puran Chen, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Yu Gao, Gunnar Söderdahl, Anders Österborg, C I Edvard Smith, Jan Vesterbacka, David Wullimann, Angelica Cuapio, Mira Akber, Gordana Bogdanovic, Sandra Muschiol, Mikael Åberg, Karin Loré, Margaret Sällberg Chen, Per Ljungman, Marcus Buggert, Soo Aleman, Hans-Gustaf Ljunggren","doi":"10.1016/j.ebiom.2024.105385","DOIUrl":"10.1016/j.ebiom.2024.105385","url":null,"abstract":"<p><strong>Background: </strong>Immunocompromised patients with primary and secondary immunodeficiencies have shown impaired responses to SARS-CoV-2 mRNA vaccines, necessitating recommendations for additional booster doses. However, longitudinal data reflecting the real-world impact of such recommendations remains limited.</p><p><strong>Methods: </strong>This study represents a two-year follow-up of the COVAXID clinical trial, where 364 of the original 539 subjects consented to participate. 355 individuals provided blood samples for evaluation of binding antibody (Ab) titers and pseudo-neutralisation capacity against both the ancestral SARS-CoV-2 strain and prevalent Omicron variants. T cell responses were assessed in a subset of these individuals. A multivariate analysis determined the correlation between Ab responses and the number of vaccine doses received, documented infection events, immunoglobulin replacement therapy (IGRT), and specific immunosuppressive drugs. The original COVAXID clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659).</p><p><strong>Findings: </strong>Several of the patient groups that responded poorly to the initial primary vaccine schedule and early booster doses presented with stronger immunogenicity-related responses including binding Ab titres and pseudo-neutralisation at the 18- and 24-month sampling time point. Responses correlated positively with the number of vaccine doses and infection. The vaccine response was blunted by an immunosuppressive state due to the underlying specific disease and/or to specific immunosuppressive treatment.</p><p><strong>Interpretation: </strong>The study results highlight the importance of continuous SARS-CoV-2 vaccine booster doses in building up and sustaining Ab responses in specific immunocompromised patient populations.</p><p><strong>Funding: </strong>The present studies were supported by the European Research Council, Karolinska Institutet, Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and the Swedish Research Council.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105385"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype.","authors":"Manukumar Honnayakanahalli Marichannegowda, Saini Setua, Meera Bose, Eric Sanders-Buell, David King, Michelle Zemil, Lindsay Wieczorek, Felisa Diaz-Mendez, Nicolas Chomont, Rasmi Thomas, Leilani Francisco, Leigh Anne Eller, Victoria R Polonis, Sodsai Tovanabutra, Alonso Heredia, Yutaka Tagaya, Nelson L Michael, Merlin L Robb, Hongshuo Song","doi":"10.1016/j.ebiom.2024.105410","DOIUrl":"10.1016/j.ebiom.2024.105410","url":null,"abstract":"<p><strong>Background: </strong>Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, virus detection and characterization were not at the earliest stages of acute infection.</p><p><strong>Methods: </strong>We identified an X4-tropic T/F HIV-1 in a participant (40700) in the RV217 acute infection cohort. Coreceptor usage was determined in TZM-bl cell line, NP-2 cell lines, and primary CD4⁺ T cells using pseudovirus and infectious molecular clones. CD4 subset dynamics were analyzed using flow cytometry. Viral load in each CD4 subset was quantified using cell-associated HIV RNA assay and total and integrated HIV DNA assay.</p><p><strong>Findings: </strong>Participant 40700 was infected by an X4 tropic HIV-1 without CCR5 using ability. This participant experienced significantly faster CD4 depletion compared to R5 virus infected individuals in the same cohort. Naïve and central memory (CM) CD4 subsets declined faster than effector memory (EM) and transitional memory (TM) subsets. All CD4 subsets, including the naïve, were productively infected. Increased CD4⁺ T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions, while most of the R5 T/F viruses in the same cohort are sensitive to the same panel of bNAbs.</p><p><strong>Interpretation: </strong>X4-tropic HIV-1 is transmissible through mucosal route in people with wild-type CCR5 genotype. The CD4 subset tropism of HIV-1 may be an important determinant for HIV-1 transmissibility and virulence.</p><p><strong>Funding: </strong>Institute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105410"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors.","authors":"Khoa Manh Dinh, Kathrine Agergård Kaspersen, Susan Mikkelsen, Bertram Dalskov Kjerulff, Jens Kjærgaard Boldsen, Mikkel Steen Petersen, Kristoffer Sølvsten Burgdorf, Erik Sørensen, Bitten Aagaard, Barbara Forman-Ankjær, Mie Topholm Bruun, Karina Banasik, Thomas Folkmann Hansen, Mette Nyegaard, Palle Duun Rohde, Søren Brunak, Henrik Hjalgrim, Sisse Rye Ostrowski, Ole Birger Pedersen, Henrik Ullum, Lise Tornvig Erikstrup, Christian Erikstrup","doi":"10.1016/j.ebiom.2024.105406","DOIUrl":"10.1016/j.ebiom.2024.105406","url":null,"abstract":"<p><strong>Background: </strong>The CC chemokine receptor 5 (CCR5) is a suggested receptor for Staphylococcus aureus leukotoxin ED. Homozygosity for the Δ32 deletion (CCR5Δ32) protects against human immunodeficiency virus infection and possibly also against leukotoxin ED. We examined the impact of CCR5Δ32 on the susceptibility to S. aureus infection, all-cause infections, and S. aureus nasal carriage, respectively, and on the concentrations of circulating chemokines in blood donors.</p><p><strong>Methods: </strong>We included 95,406 participants from the Danish Blood Donor Study (DBDS) genotyped for >650,000 single nucleotide polymorphisms. The CCR5Δ32 (rs333, MAF: 0.12) was imputed from a reference panel and validated. Infectious outcomes were identified by diagnosis codes and redeemed prescription of antibiotics in national health registers. Data on S. aureus nasal carriage and forty-seven inflammatory biomarkers were available for 6721 and 7811 participants, respectively. Cox, logistic, and linear regression models adjusted for relevant confounders were used to explore said associations.</p><p><strong>Findings: </strong>During more than 700,000 person-years of observation, we found that CCR5Δ32 was associated with neither an increased risk of redeemed dicloxacillin, hospital-treated S. aureus-associated infection (replicated in 345,996 Icelanders), redeemed antibiotics, all-cause infection, and nor with S. aureus nasal carriage. We discovered an association between CCR5Δ32 and elevated CCL4 concentrations, which were 1.26-fold higher in Δ32-heterozygotes (95%-CI: 1.23-1.30) and 2.64-fold higher in Δ32-homozygotes (95%-CI: 2.41-2.90) compared with wildtype homozygotes. Conversely, concentrations of CCL2, CXCL-10, and CCL11 were slightly lower among Δ32-heterozygotes.</p><p><strong>Interpretation: </strong>Results from this CCR5Δ32 high-prevalent cohort do not support the idea that CCR5Δ32 affects the risk of S. aureus carriage or infection to any relevant degree, in this northern European context. CCL4 was the main chemokine affected by CCR5Δ32 and was observed in higher concentration among Δ32-carriers. This study cannot rule out that S. aureus is a previous driver of CCR5Δ32 selection.</p><p><strong>Funding: </strong>The Health Research Fund of Central Denmark Region, Aarhus University, Danish Administrative Regions, Bio- and Genome Bank Denmark, Danish Blood Donor Research Foundation, Aase & Ejnar Danielsens Foundation, Højmosegård Grant, National Institute of Allergy and Infectious Diseases, and A.P. Møller Foundation for the Advancement of Medical Science.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105406"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelation embolism agents suppress clinical TACE-incited pro-metastatic microenvironment against hepatocellular carcinoma progression.","authors":"Li Song, Chunyan Zhu, Qing Shi, Yuhan Xia, Xiayi Liang, Wen Qin, Tao Ye, Biwei Yang, Xin Cao, Jinglin Xia, Kun Zhang","doi":"10.1016/j.ebiom.2024.105436","DOIUrl":"10.1016/j.ebiom.2024.105436","url":null,"abstract":"<p><strong>Background: </strong>Current embolic agents in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) encounter instability and easy leakage, discounting TACE efficacy with residual HCC. Moreover, clinical TACE aggravates hypoxia and pro-metastatic microenvironments, rendering patients with HCC poor prognosis.</p><p><strong>Methods: </strong>Herein, we developed Zein-based embolic agents that harness water-insoluble but ethanol-soluble Zein to encompass doxorubicin (DOX)-loaded mesoporous hollow MnO₂ (HMnO₂). The conditions and capacity of HMnO₂ to generate reactive oxygen species (ROS) were assayed. Mechanical examinations of Zein-HMnO₂@DOX were performed to evaluate its potential as the embolic agent. In vitro experiments were carried out to evaluate the effect of Zein-HMnO₂@DOX on HCC. The subcutaneous HCC mouse model and rabbit VX2 HCC model were established to investigate its anti-tumor and anti-metastasis efficacy and explore its potential anti-tumor mechanism.</p><p><strong>Findings: </strong>The high adhesion and crosslinking of Zein with HMnO₂@DOX impart Zein-HMnO₂@DOX with strong mechanical strength to resist deformation and wash-off. Zein gelation and HMnO₂ decomposition in response to water and acidic tumor microenvironment, respectively, enable continuous DOX release and Fenton-like reaction for reactive oxygen species (ROS) production and O₂ release to execute ROS-enhanced TACE. Consequently, Zein-based embolic agents outperform clinically-used lipiodol to significantly inhibit orthotopic HCC growth. More significantly, O₂ release down-regulates hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) and glucose transporter protein 1 (GLUT1), which thereby re-programmes TACE-aggravated hypoxic and pro-metastatic microenvironments to repress HCC metastasis towards lung. Mechanistic explorations uncover that such Zein-based TACE agents disrupt oxidative stress, angiogenesis and glycometabolism pathways to inhibit HCC progression.</p><p><strong>Interpretation: </strong>This innovative work not only provides a new TACE agent for HCC, but also establishes a new strategy to ameliorate TACE-aggravated hypoxia and metastasis motivation against clinically-common HCC metastasis after TACE operation.</p><p><strong>Funding: </strong>Excellent Young Science Fund for National Natural Science Foundation of China (82022033); National Natural Science Foundation of China (Grant No. 82373086, 82102761); Major scientific and technological innovation project of Wenzhou Science and Technology Bureau (Grant No. ZY2021009); Shanghai Young Top-Notch Talent.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105436"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrapartum antibiotic exposure and infectious diseases in childhood - a population-based cohort study.","authors":"Mikael Hakkola, Sofia Ainonen, Eveliina Ronkainen, Minna Honkila, Marika Paalanne, Tytti Pokka, Eero Kajantie, Niko Paalanne, Terhi Ruuska-Loewald","doi":"10.1016/j.ebiom.2024.105426","DOIUrl":"10.1016/j.ebiom.2024.105426","url":null,"abstract":"<p><strong>Background: </strong>Intrapartum antibiotics are used to prevent group B streptococcus disease in newborn infants. We hypothesised that intrapartum antibiotic exposure is associated with the occurrence of childhood infectious diseases because it influences the development of the gut microbiome.</p><p><strong>Methods: </strong>The cohort for this population-based study comprised vaginally delivered children born in Northern Finland in 2007-2018. We used structured electronic medical records linked to comprehensive national registers. Primary outcome was the number of infectious disease episodes leading to an emergency room visit, outpatient hospital visit, or hospitalisation from birth until five years of age.</p><p><strong>Findings: </strong>Analyses were performed on 9733 children (48.8% girls) exposed to intrapartum antibiotics and on 35,842 unexposed children (49.9% girls). Exposure to intrapartum antibiotics was associated with increased risk of any infectious disease episode at the ages 7-28 days (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.10-1.54) and 1-2 years (aIRR 1.10, 95% CI 1.02-1.18). The occurrence of urinary tract infections was associated with the exposure to intrapartum antibiotics whereas the occurrence of severe infections caused by pathogens susceptible to penicillin was reversely associated with the exposure to intrapartum antibiotics.</p><p><strong>Interpretation: </strong>Maternal intrapartum antibiotics were associated with the occurrence of infectious diseases in the offspring. The observed associations appeared to depend on bacterial pathogens and their antimicrobial susceptibility to penicillin.</p><p><strong>Funding: </strong>Pediatric Research Foundation, Alma och K.A. Snellman Foundation, Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Medical Foundation, Academy of Finland, Finland.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105426"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell atlas reveals multilayered metabolic heterogeneity across tumour types.","authors":"Zhe Zhou, Di Dong, Yuyao Yuan, Juan Luo, Xiao-Ding Liu, Long-Yun Chen, Guangxi Wang, Yuxin Yin","doi":"10.1016/j.ebiom.2024.105389","DOIUrl":"10.1016/j.ebiom.2024.105389","url":null,"abstract":"<p><strong>Background: </strong>Metabolic reprogramming plays a pivotal role in cancer progression, contributing to substantial intratumour heterogeneity and influencing tumour behaviour. However, a systematic characterization of metabolic heterogeneity across multiple cancer types at the single-cell level remains limited.</p><p><strong>Methods: </strong>We integrated 296 tumour and normal samples spanning six common cancer types to construct a single-cell compendium of metabolic gene expression profiles and identify cell type-specific metabolic properties and reprogramming patterns. A computational approach based on non-negative matrix factorization (NMF) was utilised to identify metabolic meta-programs (MMPs) showing intratumour heterogeneity. In-vitro cell experiments were conducted to confirm the associations between MMPs and chemotherapy resistance, as well as the function of key metabolic regulators. Survival analyses were performed to assess clinical relevance of cellular metabolic properties.</p><p><strong>Findings: </strong>Our analysis revealed shared glycolysis upregulation and divergent regulation of citric acid cycle across different cell types. In malignant cells, we identified a colorectal cancer-specific MMP associated with resistance to the cuproptosis inducer elesclomol, validated through in-vitro cell experiments. Furthermore, our findings enabled the stratification of patients into distinct prognostic subtypes based on metabolic properties of specific cell types, such as myeloid cells.</p><p><strong>Interpretation: </strong>This study presents a nuanced understanding of multilayered metabolic heterogeneity, offering valuable insights into potential personalized therapies targeting tumour metabolism.</p><p><strong>Funding: </strong>National Key Research and Development Program of China (2021YFA1300601). National Natural Science Foundation of China (key grants 82030081 and 81874235). The Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project (JCYJ20220818102811024). The Lam Chung Nin Foundation for Systems Biomedicine.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105389"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}