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| Open AccessDeviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic
Non-pharmaceutical interventions for COVID-19 also impacted the transmission of other viruses including respiratory syncytial virus (RSV). Here the authors describe the changing epidemiology, clinical severity, and genetic diversity of RSV in Chicago, Illinois, from July 2010 to April 2023.
- Estefany Rios-Guzman
- , Lacy M. Simons
- & Judd F. Hultquist
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Comment
| Open AccessReporting outcome comparisons by sex in oncology clinical trials
Many aspects of human health and disease are influenced by sex as a biological variable and gender as a social construct. A recent study from Nature Communications reported the landscape of outcome comparisions by sex in oncology clinical trials, highlighting the need for a more thorough reporting of sex differences.
- Guo Zhao
- , Yuning Wang
- & Ning Li
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Article
| Open AccessPolygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis
Colitis is one of the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors. Here the authors show that a polygenic risk score for ulcerative colitis can predict immune checkpoint inhibitor-mediated colitis in patients with cancer.
- Pooja Middha
- , Rohit Thummalapalli
- & Elad Ziv
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Article
| Open AccessLong-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study
Here the authors study recovery from mild to moderate Omicron breakthrough infection at six months post infection. Serum proteomics, PBMC single-cell transcriptomics and clinical parameters indicate slow recovery with coagulation abnormalities and an imbalance of the immune response and metabolism remaining.
- Yanhua Li
- , Shijie Qin
- & George Fu Gao
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Article
| Open AccessOptimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation
Nirmatrelvir/ritonavir can reduce COVID-19 severity when initiated within five days of symptom onset but the optimal timing within this window is unknown. Here, the authors emulate a randomised trial using electronic health records from Hong Kong and find evidence for a benefit of early treatment initiation.
- Carlos K. H. Wong
- , Jonathan J. Lau
- & Joseph T. Wu
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Article
| Open AccessEvaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity
There is a need for an accurate measure of pulmonary oxygenation function that can be used as an intermediate endpoint in pragmatic clinical trials, to increase statistical power and efficiency. Here, the authors show that the S/F94, a modification of the S/F ratio, is a simple, meaningful and effective intermediate outcome measure.
- Maaike C. Swets
- , Steven Kerr
- & J. Kenneth Baillie
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Article
| Open AccessReconstructing disease dynamics for mechanistic insights and clinical benefit
Understanding disease progression dynamics is critical for diagnostics and treatment, but capturing dynamics is difficult. Here, the authors present a method for modelling disease progression from high dimensional molecular data that enables patient stratification and high-risk disease state identification, showcased in bladder cancer.
- Amit Frishberg
- , Neta Milman
- & Shai S. Shen-Orr
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Article
| Open AccessNeoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial
Recent evidence suggests the feasibility of neoadjuvant immune checkpoint inhibitors plus chemotherapy-based therapy for patients with early triple-negative breast cancer (TNBC). Here the authors report the results of a single-arm phase II trial of neoadjuvant camrelizumab (anti-PD-1) plus nab-paclitaxel and epirubicin for early TNBC.
- Chengzheng Wang
- , Zhenzhen Liu
- & Min Yan
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Article
| Open AccessThe Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a Randomized Clinical Trial
Genotype patterns may modify diet effects on weight loss, with greater weight loss on genotype-concordant diets. Here, the authors show that with the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater weight loss on genotype-concordant diets.
- Christoph Höchsmann
- , Shengping Yang
- & Corby K. Martin
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Article
| Open AccessA hybrid register and questionnaire study of Covid-19 and post-acute sick leave in Denmark
Authors utilise a questionnaire-based approach to survey self-reported, post-acute sick leave and risk factors in cases of SARS-CoV-2.
- Elisabeth O’Regan
- , Ingrid Bech Svalgaard
- & Anders Hviid
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Article
| Open AccessLongitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy
Immune checkpoint blockade therapy improved the survival rates of non-small cell lung cancer but only a proportion of patients benefit. Here authors follow the humoral and cellular immunological parameters of patients undergoing anti-PD1 therapy longitudinally and find that levels and functional properties of cytotoxic T cells, and especially CD8+CD101hiTIM3+ cells determine the response.
- Elaine Lai-Han Leung
- , Run-Ze Li
- & Liang Liu
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Article
| Open AccessPredicting in-hospital outcomes of patients with acute kidney injury
Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. Here, the authors show a deep learning model that can identify patients with acute kidney injury (AKI) who are at high risk of death or dialysis at certain time points.
- Changwei Wu
- , Yun Zhang
- & Guisen Li
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Article
| Open AccessLong-term exposure to air pollution and severe COVID-19 in Catalonia: a population-based cohort study
In this study, the authors investigate the relationship between exposure to air pollutants and severe COVID-19 disease using data from a cohort of ~5 million people in Catalonia, Spain. They find that long-term exposure to pollutants is associated with a higher risk of COVID-19-related hospitalization, death, intensive care admission, and length of hospital stay.
- Otavio Ranzani
- , Anna Alari
- & Cathryn Tonne
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Article
| Open AccessA randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes
In a multicenter randomized trial, researchers found that electronic alerts increased the rate of discontinuation of potential nephrotoxins. This did not translate into improved clinical outcomes, except among those exposed to proton-pump inhibitors.
- F. Perry Wilson
- , Yu Yamamoto
- & Ugochukwu Ugwuowo
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Article
| Open AccessTotal escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient
Antibodies against SARS-CoV-2 can be used to treat infections but there is a risk of driving viral resistance to antibodies. Here the authors characterise SARS-CoV-2 escape mutants from an immunocompromised patient treated with anti-SARS-CoV-2 antibodies using mouse protection studies and structural prediction.
- Lena Jaki
- , Sebastian Weigang
- & Jonas Fuchs
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Article
| Open AccessPost-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+β7 integrin+ T cells and anti-SARS-CoV-2 IgA response
Post-acute sequelae SARS-CoV-2 (PASC), also known as long COVID is a chronic and often debilitating condition that develops following acute disease. Here authors show that individuals who suffer from PASC symptoms at six month following infection are characterized by persisting immunological disfunction, affecting cellular and humoral components of mucosal immunity.
- André Santa Cruz
- , Ana Mendes-Frias
- & Ricardo Silvestre
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Article
| Open AccessCharacterisation of ASD traits among a cohort of children with isolated fetal ventriculomegaly
Isolated fetal ventriculomegaly is the most common antenatally-diagnosed brain abnormality. Here, the authors show that isolated fetal ventriculomegaly is associated with autism spectrum disorder traits.
- Vanessa Kyriakopoulou
- , Alice Davidson
- & Mary A. Rutherford
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Article
| Open AccessEvaluation of mortality attributable to SARS-CoV-2 vaccine administration using national level data from Qatar
This study assesses the probability that deaths following a COVID-19 vaccination are attributable to the vaccine. The authors review all deaths that occurred within 30 days of vaccine receipt in Qatar until June 2022 and find that deaths attributable to vaccination are extremely rare.
- Adeel A. Butt
- , Mylai D. Guerrero
- & Abdul-Badi Abou-Samra
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Article
| Open AccessThrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom
Population-based studies can provide information on the safety of COVID-19 vaccines. Here the authors report the rates thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom and compare them with the background (expected) rates in the general population.
- Edward Burn
- , Xintong Li
- & Daniel Prieto-Alhambra
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Article
| Open AccessLipidomic signatures align with inflammatory patterns and outcomes in critical illness
Alterations in lipid metabolism and circulating lipid species have been reported in patients with acute critical illness. Here the authors show that selective rise in systemic phosphatidylethanolamine levels is a common feature of critical illness that associates with worse clinical outcomes.
- Junru Wu
- , Anthony Cyr
- & Mieshia Beamon
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Perspective
| Open AccessKey considerations to reduce or address respondent burden in patient-reported outcome (PRO) data collection
The collection of patient-reported outcomes (PROs) may capture patients’ assessments of their health status. Here authors highlight PRO-specific issues that should be considered to minimise respondent burden in clinical trials and routine care.
- Olalekan Lee Aiyegbusi
- , Jessica Roydhouse
- & Melanie Calvert
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Article
| Open AccessReproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions
Analyses of real-world evidence from digital clinical practice data provide important insights for healthcare decision makers. Here, authors test reproducibility of 150 peer-reviewed studies, reporting strong reproducibility, which could be further improved through more complete reporting in future original studies
- Shirley V. Wang
- , Sushama Kattinakere Sreedhara
- & Deborah Zarin
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Article
| Open AccessImmunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV
HIV infection may affect the immune response to vaccination. Here the authors show that humoral response in persons living with HIV after the third dose of a SARS-CoV-2 vaccine is strong and higher than that achieved with the second dose, while cell-mediated immunity remains stable.
- Alessandra Vergori
- , Alessandro Cozzi Lepri
- & Eleonora Tartaglia
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Article
| Open AccessSARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort
Here the authors provide data from a sub-cohort of the Virus Watch study (19,556 adults) who completed at-home capillary blood sampling on a monthly basis and describe an association between anti-spike antibody levels and risk of SARS-CoV-2 infection.
- Robert W. Aldridge
- , Alexei Yavlinsky
- & Andrew Hayward
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Article
| Open AccessDuration of protection of CoronaVac plus heterologous BNT162b2 booster in the Omicron period in Brazil
Primary CoronaVac vaccination followed by a BNT162b2 booster dose confers protection against some SARS-CoV-2 variants but its effectiveness against Omicron is unknown. Here, the authors show that this combination confers a high level of protection against severe outcomes for up to 120 days, with evidence of waning for those aged 80 or older.
- Thiago Cerqueira-Silva
- , Vinicius de Araujo Oliveira
- & Manoel Barral-Netto
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Article
| Open AccessAddressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer
Real-world data (RWD) based control arms provide an option to compare the effectiveness of single-arm trials. By performing multiple quantitative bias analyses to alleviate concerns about trial-RWD comparability, here the authors show that the RET inhibitor pralsetinib provides survival benefit in patients with RET fusion-positive non-small cell lung cancer from the ARROW single-arm trial, (NCT03037385) when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts.
- Sanjay Popat
- , Stephen V. Liu
- & Vivek Subbiah
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Article
| Open AccessEffectiveness of BBIBP-CorV vaccine against severe outcomes of COVID-19 in Abu Dhabi, United Arab Emirates
There is limited real-world evidence for the effectiveness of the BBIBP-CorV (Sinopharm) vaccine against severe COVID-19 disease. Here, the authors use data from Abu Dhabi and estimate effectiveness at 80% against hospitalization; 86% against critical care admission and 84% against death.
- Nawal Al Kaabi
- , Abderrahim Oulhaj
- & Walid Zaher
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Article
| Open AccessInhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis
Sarcoidosis is a heterogenous disorder often treated with glucocorticoids. Here the authors show, in an open label, non-randomized, single arm clinical trial involving 10 patients, that treatment with tofacitinib, a Janus kinase inhibitor, is associated with improved clinical symptoms and reduced activity of Th1 cytokines such as IFN-γ and IL-12.
- William Damsky
- , Alice Wang
- & Brett King
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Article
| Open AccessComparative effectiveness over time of the mRNA-1273 (Moderna) vaccine and the BNT162b2 (Pfizer-BioNTech) vaccine
In this retrospective cohort study, Islam et al. estimate the effectiveness of two mRNA-based COVID-19 vaccines in over 3.5 million fully vaccinated individuals and find no differences in vaccine effectiveness for protection against hospitalization, ICU admission, or death/hospice transfer.
- Nazmul Islam
- , Natalie E. Sheils
- & Kenneth Cohen
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Article
| Open AccessNationally representative SARS-CoV-2 antibody prevalence estimates after the first epidemic wave in Mexico
SARS-CoV-2 seroprevalence surveys provide estimates of the extent of prior infection in a population. In this nationally representative survey from Mexico, the authors estimate seroprevalence after the first epidemic wave at ~25%, with variation by region, age, socioeconomic status, and education level.
- Ana Basto-Abreu
- , Martha Carnalla
- & Andrés Sanchez-Pájaro
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Article
| Open AccessImpacts of rapid mass vaccination against SARS-CoV2 in an early variant of concern hotspot
Schwaz, Austria, experienced SARS-CoV-2 outbreaks caused by variants of concern in early 2021 and conducted a mass vaccination campaign in response, with 70% of the adult population vaccinated after 5 days. Here, the authors show that this campaign resulted in reduced infections and hospitalisations.
- Jörg Paetzold
- , Janine Kimpel
- & Hannes Winner
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Article
| Open AccessMultimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong
Adverse events resulting from COVID-19 vaccination are a public health concern and it is not known whether pre-existing conditions may impose an increased risk. Here, using electronic health records from Hong Kong, the authors show that adverse events are rare for all groups, and there is no evidence of risk modification due to multimorbidity.
- Francisco Tsz Tsun Lai
- , Lei Huang
- & Ian Chi Kei Wong
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Article
| Open AccessA phase 2 single center open label randomised control trial for convalescent plasma therapy in patients with severe COVID-19
Convalescent plasma therapy (CPT) is used to treat patients with Covid-19, but evidence for clinical benefit from clinical trials is divergent. Here the authors report in that CPT treatment does not affect mortality in patients with severe Covid-19 in phase 2 single center open label randomised controlled trial.
- Yogiraj Ray
- , Shekhar Ranjan Paul
- & Dipyaman Ganguly
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Article
| Open AccessDynamics of spike-and nucleocapsid specific immunity during long-term follow-up and vaccination of SARS-CoV-2 convalescents
Waning immunity to SARS-CoV-2 is of concern. Here the authors follow spike- and nucleocapsid specific immunity in convalescent individuals for 9 months observing a decline in antibody levels but persisting T cell response. Vaccination approximately 11 months after infection boosts antibody and T cell immunity.
- Nina Koerber
- , Alina Priller
- & Percy A. Knolle
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Article
| Open AccessBurdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status
Post-acute sequelae of COVID-19 (PASC, or ‘Long COVID’) has caused concern but the burden and risk factors are not well understood. Here, the authors use US electronic health record data and estimate an overall burden of PASC of ~7% at six months, with variation by severity of acute infection, baseline health status and demographics.
- Yan Xie
- , Benjamin Bowe
- & Ziyad Al-Aly
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Article
| Open AccessA single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial
Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has caused outbreaks in various regions of the world. Here the authors present safety and immunogenicity data from a phase 1 trial with the simian adenovirus vectored vaccine ChAdOx1 Chik, showing induction of neutralizing antibodies to four CHIKV lineages.
- Pedro M. Folegatti
- , Kate Harrison
- & Arturo Reyes-Sandoval
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Article
| Open AccessDeep convolutional neural networks to predict cardiovascular risk from computed tomography
Coronary artery calcium is an accurate predictor of cardiovascular events but this information is not routinely quantified. Here the authors show a robust and time-efficient deep learning system to automatically quantify coronary calcium on CT scans and predict cardiovascular events in a large, multicentre study.
- Roman Zeleznik
- , Borek Foldyna
- & Hugo J. W. L. Aerts
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Article
| Open AccessDeep transfer learning for reducing health care disparities arising from biomedical data inequality
Developing machine learning models that work equally well for all ethnic groups is of crucial importance to health disparity prevention and reduction. Here, using an extensive set of machine learning experiments on cancer omics data, the authors find that transfer learning can improve model performance for data-disadvantaged ethnic groups.
- Yan Gao
- & Yan Cui
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Article
| Open AccessLymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics
A non-destructive and efficient method for predicting the risk of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) patients is highly needed. Here, the authors develop a transfer learning radiomics model for preoperative prediction of LNM in patients with PTC in a multicenter scenario.
- Jinhua Yu
- , Yinhui Deng
- & Cai Chang
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Article
| Open AccessA randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis
Here, the authors report the results of a randomized, placebo controlled trial of children with acute gastroenteritis who were treated with a probiotic and find no virus-specific beneficial effects attributable to the probiotic, either in reducing clinical symptoms or clearance of viral nucleic acid from stool specimens.
- Stephen B. Freedman
- , Jianling Xie
- & Marc H. Gorelick
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Article
| Open AccessHorse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species
Antivenoms, obtained by venom immunization, have narrow species coverage due to low immunogenicity of venom neurotoxins. Here the authors immunize horses with a designed recombinant consensus neurotoxin, and the resulting antisera protect mice from envenomation by a broad spectrum of elapid snakes.
- Guillermo de la Rosa
- , Felipe Olvera
- & Gerardo Corzo
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Article
| Open AccessRepeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans
Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine platform.
- Surender Khurana
- , Megan Hahn
- & Hana Golding
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Article
| Open AccessMapping vaccination coverage to explore the effects of delivery mechanisms and inform vaccination strategies
The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. Here, the authors evaluate the relative effectiveness of two major vaccine delivery strategies, namely routine immunization and supplementary immunization activities in five study countries.
- C. Edson Utazi
- , Julia Thorley
- & Andrew J. Tatem
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Article
| Open AccessSocial networks and risk of delayed hospital arrival after acute stroke
Rapid arrival to hospital after stroke is critical for patients to receive effective treatment. Here, the authors examine how stroke patients’ social network structure relates to stroke arrival time, and show that small and close-knit personal networks predict delayed arrival.
- Amar Dhand
- , Douglas Luke
- & Jin-Moo Lee
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Article
| Open AccessConvulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
The etiology of focal cortical dysplasia (FCD) is not fully understood. Here authors generate an mTORC1 overactivation mouse model that recapitulates hallmarks of type II FCDs, including spontaneous seizures, and suggest that neuronal defects, rather than macrostructural changes, lead to seizures.
- Lawrence S. Hsieh
- , John H. Wen
- & Angelique Bordey
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Article |
Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer
Phenotypic and genetic heterogeneity of cells within a tumour is thought to mediate treatment resistance and contribute to cancer progression. Here the authors show that genetic diversity in pediatric cancers is common after chemotherapy and can be quantified to predict survival.
- Linda Holmquist Mengelbier
- , Jenny Karlsson
- & David Gisselsson
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Article
| Open AccessCombining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes
The myelodysplastic syndromes (MDS) are a heterogeneous group of chronic blood cancers. Here, the authors analyse genomic and gene expression data from MDS patients to investigate how driver mutations alter gene expression, diagnostic clinical variables and survival.
- Moritz Gerstung
- , Andrea Pellagatti
- & Jacqueline Boultwood