Featured
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Article
| Open AccessA metabolomic profile of biological aging in 250,341 individuals from the UK Biobank
The metabolomic changes over the course of aging are complex. Here, the authors present a comprehensive metabolomic profile of aging and construct a metabolomic aging score, which has potential for personalized aging monitoring and early disease-risk identification.
- Shiyu Zhang
- , Zheng Wang
- & Bin Li
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Article
| Open AccessLewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer’s disease
Cognitively impaired subjects with both Alzheimer’s disease and Lewy body pathology determined using in vivo CSF biomarkers showed faster global cognitive decline and more posterior cortical hypometabolism compared to those with AD pathology only.
- Lyduine E. Collij
- , Sophie E. Mastenbroek
- & Oskar Hansson
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Article
| Open AccessVirtual birefringence imaging and histological staining of amyloid deposits in label-free tissue using autofluorescence microscopy and deep learning
Detecting amyloid deposits in tissue with Congo red can be limited by several factors, which can potentially lead to false diagnoses. Here, the authors use virtual birefringence imaging and virtual Congo red staining using autofluorescence of label-free human tissue, highlighting amyloid deposits in a consistent manner.
- Xilin Yang
- , Bijie Bai
- & Aydogan Ozcan
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Article
| Open AccessClearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer’s disease progression
Impaired Aβ clearance in late-onset Alzheimer’s disease (AD) affects progression. Here, the authors show that CD14 + CD16+ monocytes carry Aβ in peripheral circulation and CSF in AD, suggesting a role in Aβ clearance.
- Xin Huang
- , Chris Fowler
- & Ben J. Gu
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Article
| Open AccessNon-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease
Pompe disease (PD) is a rare disorder that leads to progressive muscle weakness if left untreated. Here, the authors use multispectral optoacoustic tomography (MSOT) to map and quantify the composition of affected muscle tissue to determine disease severity and potentially monitor future therapies.
- Lina Tan
- , Jana Zschüntzsch
- & Ferdinand Knieling
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Article
| Open AccessGlutathione peroxidase 3 is a potential biomarker for konzo
The search for biomarkers associated with konzo disease has been a long-standing question within the research community. Here, the authors have uncovered a potential biomarker for konzo that is associated with the ability to manage oxidative damage.
- Matthew S. Bramble
- , Victor Fourcassié
- & Arnaud Droit
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Article
| Open AccessscEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood
Here, the authors generate a single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. They next develop scEpiAge, a single-cell DNA methylation age predictor.
- Marc Jan Bonder
- , Stephen J. Clark
- & Ferdinand von Meyenn
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Article
| Open AccessAdipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality
Calorie burning is normally turned off in thermogenic brown fat at warm temperatures. Here the authors show that adipocyte oxygen sensing directly boosts brown fat calorie burning, even at warm temperatures.
- Rongling Wang
- , Mario Gomez Salazar
- & Zoi Michailidou
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Article
| Open AccessEarly biological markers of post-acute sequelae of SARS-CoV-2 infection
Biological determinants for developing post-acute sequelae of SARS-CoV-2 infection are largely unclear. Here, by comparing markers during acute infection in individuals who developed PASC with those who recovered, the authors found that early viral dynamics and immune responses might play a role in PASC pathogenesis.
- Scott Lu
- , Michael J. Peluso
- & J. Daniel Kelly
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Article
| Open AccessGut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles
Here, the authors develop the Gut Microbiome Wellness Index 2 (GMWI2), an enhanced version of the original GMWI prototype, designed as a disease-agnostic health status indicator based on gut microbiome taxonomic profiles.
- Daniel Chang
- , Vinod K. Gupta
- & Jaeyun Sung
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Article
| Open AccessPlasma proteomics of acute tubular injury
Acute tubular injury (ATI) significantly contributes to many kidney diseases. Here, the authors identify several immune response and cellular stress plasma proteins linked to ATI severity and acute kidney injury, which may aid in non-invasive ATI assessment.
- Insa M. Schmidt
- , Aditya L. Surapaneni
- & Sushrut S. Waikar
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Article
| Open AccessUnbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark
Multiple cellular pathways are altered in cancer and identifying them is relevant for prognosis and therapy. Here, the authors develop Benchmark and Pathway Ensemble Tool (PET), two computational approaches to optimise pathway discovery in cancer and predict related biomarkers and therapeutic avenues.
- Luopin Wang
- , Aryamav Pattnaik
- & Majid Kazemian
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Article
| Open AccessTislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study
Monotherapy with immune checkpoint inhibitors has shown limited clinical activity in patients with microsatellite stable (MSS) colorectal cancer (CRC). Here the authors report the results of a clinical trial of tislelizumab (anti-PD1) in combination with cetuximab (anti-EGFR) and irinotecan in patients with refractory MSS and RAS wild-type metastatic CRC.
- Xiaojing Xu
- , Luoyan Ai
- & Tianshu Liu
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Article
| Open AccessA Platelet Reactivity ExpreSsion Score derived from patients with peripheral artery disease predicts cardiovascular risk
Platelet hyperreactivity is associated with cardiovascular events in patients with PAD. Here the authors derive and validate a circulating platelet genetic signature to discriminate platelet hyperreactivity and cardiovascular risk.
- Jeffrey S. Berger
- , Macintosh G. Cornwell
- & Tessa J. Barrett
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Article
| Open AccessPeptide clustering enhances large-scale analyses and reveals proteolytic signatures in mass spectrometry data
Studies of protein degradation through peptidomic analyses are complicated by the vast potential peptidomic landscapes. Here, the authors present a method that cluster peptides, simplifying down-stream analyses and apply it identify pathogen-specific peptide patterns in infected wounds.
- Erik Hartman
- , Fredrik Forsberg
- & Artur Schmidtchen
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Article
| Open AccessClinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas
Efficient and non-invasive, liquid biopsy methods could greatly improve the molecular classification of gliomas. Here, the authors develop an RNA-based Droplet Digital PCR assay to detect the key IDH1.R132H mutation in plasma-derived extracellular vesicles from glioma patients with high sensitivity, allowing accurate diagnosis, prognostication and longitudinal monitoring.
- Syeda Maheen Batool
- , Ana K. Escobedo
- & Bob S. Carter
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Article
| Open AccessIn silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications
While alternative splicing is known to drive oncogenesis and be a source of potential therapeutic targets, identifying such drivers on a genome-wide scale has proven difficult. Here, the authors present a computational approach to identify potential cancer-driver exons and evaluate applicability as therapeutic targets.
- Miquel Anglada-Girotto
- , Ludovica Ciampi
- & Luis Serrano
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Article
| Open AccessEnd-to-end reproducible AI pipelines in radiology using the cloud
A significant portion of the scientific literature on AI for radiology lacks transparency and reproducibility, which hampers sustained progress toward clinical translation. Here, the authors offer a blueprint for transparent AI pipelines on cloud platforms, focusing on lung cancer prediction and biomarker discovery.
- Dennis Bontempi
- , Leonard Nuernberg
- & Hugo J. W. L. Aerts
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Article
| Open AccessAI hybrid survival assessment for advanced heart failure patients with renal dysfunction
Here the authors show an AI-powered assessment system (AIHFLevel, www.hf-ai-survival.com) empowering healthcare professionals for continuous risk monitoring and prognosis assessment of patients who have advanced heart failure with renal dysfunction.
- Ge Zhang
- , Zeyu Wang
- & Junnan Tang
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Article
| Open AccessTranscriptomic classification of diffuse large B-cell lymphoma identifies a high-risk activated B-cell-like subpopulation with targetable MYC dysregulation
Researchers identified 7 biological group of diffuse large B-cell lymphoma, one with poor prognosis. They developed a gene expression classifier to detect these groups, potentially improving prognosis and future treatments for the high-risk patients.
- Matthew E. Stokes
- , Kerstin Wenzl
- & Anita K. Gandhi
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Article
| Open AccessDNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation
Cell free DNA fragmentation is a promising biomarker for disease, but its epigenetic regulation is incompletely understood. Here, the authors investigated the effects of DNA methylation in the production of cfDNA fragmentation, and corelate these changes with gene expression in human cancer.
- Michaël Noë
- , Dimitrios Mathios
- & Victor E. Velculescu
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Article
| Open AccessDiagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement
Aberrant changes in DNA methylation have been implicated in various neurodevelopmental disorders but remain under studied in developmental and epileptic encephalopathies. Here, the authors demonstrate the diagnostic utility of genome-wide DNA methylation analyses toward identifying molecular etiologies in developmental and epileptic encephalopathies.
- Christy W. LaFlamme
- , Cassandra Rastin
- & Heather C. Mefford
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Article
| Open AccessWireless ear EEG to monitor drowsiness
Neural wearables can enable life-saving drowsiness monitoring. This work showcases an in-ear, dry-electrode earpiece used to monitor drowsiness for 35 hours across 9 subjects. This data was used to train offline machine learning classifiers and achieve an average accuracy of >90% across all models.
- Ryan Kaveh
- , Carolyn Schwendeman
- & Rikky Muller
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Review Article
| Open AccessVentilator-associated pneumonia: pathobiological heterogeneity and diagnostic challenges
Ventilator-associated pneumonia (VAP) is a nosocomial infection that significantly affects critically ill patients undergoing mechanical ventilation in the Intensive Care Unit (ICU). This review presents the diagnostic challenges associated with VAP in ICU.
- Fiona Howroyd
- , Cyril Chacko
- & Tonny Veenith
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Article
| Open AccessGenome-wide discovery for biomarkers using quantile regression at biobank scale
Here, the authors propose using quantile regression for genome-wide association studies with quantitative traits in UK Biobank, showing its advantages over linear regression in handling nonnormal distributions and identifying heterogeneous genetic effects.
- Chen Wang
- , Tianying Wang
- & Iuliana Ionita-Laza
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Article
| Open AccessPolygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events
In this study, the authors showed how common genetic factors in the form of epilepsy polygenic risk scores influence epilepsy risk across lifetime and after unspecified seizure events. This could eventually help epilepsy diagnosis.
- Henrike O. Heyne
- , Fanny-Dhelia Pajuste
- & Mark J. Daly
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Article
| Open AccessDeterminants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants
Though the role of transthyretin (TTR) in the development of cardiac amyloidosis has been recognized, the determinants of TTR levels remain unexplored. Here, the authors present the clinical correlates of transthyretin levels and show that reduced TTR levels are associated with an increase risk of cardiovascular disease and mortality.
- Naman S. Shetty
- , Mokshad Gaonkar
- & Pankaj Arora
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Article
| Open AccessA multi-classifier system integrated by clinico-histology-genomic analysis for predicting recurrence of papillary renal cell carcinoma
Renal cell carcinoma consists of several subtypes, and recurrence is highly dependent on subtype. Here, the authors develop a multi-classifier using imaging, lncRNA and clinical data to predict recurrence in papillary renal cell carcinoma.
- Kang-Bo Huang
- , Cheng-Peng Gui
- & Jun-Hang Luo
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Article
| Open AccessWhole cervix imaging of collagen, muscle, and cellularity in term and preterm pregnancy
Diffusion basis spectrum imaging (DBSI) is an MRI technique that offers non-invasive insights into cervical structure by imaging cellularity, collagen, and muscle fibers. Here, the authors apply DBSI on the human cervix during pregnancy both ex vivo and in vivo and reveal microstructural differences between term and preterm deliveries.
- Wenjie Wu
- , Zhexian Sun
- & Yong Wang
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Article
| Open AccessIntegrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk
The relationship between tissue-specific DNA methylation and cancer risk remains to be elucidated. Here, the authors predict DNA methylation at CpG sites for seven cancer types and investigate how these influence cancer risk.
- Yaohua Yang
- , Yaxin Chen
- & Jirong Long
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Article
| Open AccessNeurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm
Machine learning can be used to identify subtypes of psychiatric disease. Here the authors identified two neurostructural subgroups in schizophrenia, each showing reproducibility and generalizability across different collection locations and illness stages, using the SuStain algorithm.
- Yuchao Jiang
- , Cheng Luo
- & Jianfeng Feng
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Article
| Open AccessImmunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma
Changes in the tumour microenvironment have been associated with response and resistance to immunotherapy. Here, by performing longitudinal transcriptomic and spatial analysis, the authors report the exploratory analysis of their phase II trial of neoadjuvant chemotherapy alone or in combination with pembrolizumab (anti-PD1) in patients with advanced high-grade ovarian carcinoma.
- Olivia Le Saux
- , Maude Ardin
- & Isabelle Ray-Coquard
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Article
| Open AccessClinical features associated with NeoRAS wild-type metastatic colorectal cancer A SCRUM-Japan GOZILA substudy
RAS mutations have been shown to be lost after first line treatment for metastatic colorectal cancer. Here, the authors leverage the GOZILA study to identify these patients and identify their association with other risk factor.
- Hiroki Osumi
- , Eiji Shinozaki
- & Takayuki Yoshino
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Article
| Open AccessTherapeutic potential of the secreted Kazal-type serine protease inhibitor SPINK4 in colitis
The early stages of inflammatory bowel disease involve mucus injury and depletion of goblet cells. Here, the authors show that SPINK4 could serve as a serological biomarker of IBD and holds therapeutic potential for goblet cell regeneration via intrinsic EGFR activation under colitic conditions
- Ying Wang
- , Jing Han
- & Shenghong Zhang
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Article
| Open AccessPatritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response
Patritumab deruxtecan (HER3-DXd) is a promising therapy for breast cancer, targeting HER3. Here, the authors analyse the genomic factors that affect the response to HER3-DXd in patients with early-stage HER2-negative breast cancer as part of the SOLTI-1805 TOT-HER3 clinical trial and report outcomes for Part B of the trial using lower HER3-DXd dose in patients with HER2-negative breast cancer.
- Fara Brasó-Maristany
- , Juan Manuel Ferrero-Cafiero
- & Mafalda Oliveira
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Article
| Open AccessPrecision arbovirus serology with a pan-arbovirus peptidome
Arboviruses are transmitted by arthropods and include a number of critical human and zoonotic pathogens. Here the authors report a phage display library, ArboScan, for evaluating antibody binding to the peptidome of 691 human and zoonotic arthropod borne viruses, and use it to profile anti-arbovirus antibodies from diverse samples.
- William R. Morgenlander
- , Wan Ni Chia
- & Matthew L. Robinson
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Article
| Open AccessCirculating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma
ctDNA is a known poor prognostic factor for multiple cancer types, but variant-specificity is unknown. Here, the authors show variant-specific association of ctKRAS levels with survival in previously untreated metastatic pancreatic ductal adenocarcinoma patients in multiple cohorts.
- Jacob E. Till
- , Lee McDaniel
- & Erica L. Carpenter
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Article
| Open AccessPlasma metabolomics reveals the shared and distinct metabolic disturbances associated with cardiovascular events in coronary artery disease
Investigating metabolic disturbances in coronary artery disease (CAD) may allow the identifications of new prognostic biomarkers. Here the authors perform a metabolomics study to highlight the shared and distinct metabolites characterizing risks of several cardiovascular events in CAD patients.
- Jiali Lv
- , Chang Pan
- & Yuguo Chen
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Article
| Open AccessDirectional integration and pathway enrichment analysis for multi-omics data
The data fusion method presented here integrates multi-omics datasets for gene prioritisation, biomarker discovery, and pathway enrichment analysis by finding genes and proteins with significant and directionally consistent changes across the data modalities.
- Mykhaylo Slobodyanyuk
- , Alexander T. Bahcheli
- & Jüri Reimand
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Article
| Open AccessSingle-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome
Tumour-associated myeloid cells have been linked to patient outcome and treatment response in multiple cancer types. Here, the authors use deconvolution of single cell RNA-sequencing data to identify myeloid populations which are prognostic across cancer types.
- Gabriela Rapozo Guimarães
- , Giovanna Resk Maklouf
- & Mariana Boroni
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Perspective
| Open AccessNeuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions
Biomarkers are needed in Parkinson’s for accurate diagnosis, to monitor progression and for targeted treatment. The authors reflect on recent imaging and fluid biomarkers for Parkinson’s and consider challenges in bringing them into clinical use.
- Angeliki Zarkali
- , George E. C. Thomas
- & Rimona S. Weil
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Article
| Open AccessBaseline levels and longitudinal changes in plasma Aβ42/40 among Black and white individuals
Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics’ Precivity AD test for Aβ42 and Aβ40. Compared to white individuals, Black individuals had higher average plasma Aβ42/40 levels at baseline, consistent with a lower average level of amyloid pathology.
- Chengjie Xiong
- , Jingqin Luo
- & Suzanne E. Schindler
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Article
| Open AccessBiomarkers of mortality in adults and adolescents with advanced HIV in sub-Saharan Africa
In this study, by analysing immune biomarkers in a cohort of people with advanced HIV, the authors show that elevated levels of some biomarkers at baseline were associated with either increased (CRP, IFN-ƴ, IL-6 and IP-10) or decreased (IL-23, IL-2 and RANTES) likelihood of all-cause mortality.
- Victor Riitho
- , Roisin Connon
- & Andrew J. Prendergast
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Article
| Open AccessRestricting datasets to classifiable samples augments discovery of immune disease biomarkers
Immune disease-associated biomarker values are commonly more variable in affected compared to unaffected patient populations, which limits a biomarker’s informative range. Here, the authors formalise a computational solution that splits datasets into informative and uninformative subsets to improve biomarker discovery and performance of multivariate predictive models.
- Gunther Glehr
- , Paloma Riquelme
- & James A. Hutchinson
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Article
| Open AccessAI-based histopathology image analysis reveals a distinct subset of endometrial cancers
Endometrial cancer (EC) has four molecular subtypes; of these, the No Specific Molecular Profile (NSMP) subtype encompasses patients with heterogeneous outcomes. Here, the authors use artificial intelligence and histopathology images to differentiate p53abn and NSMP subtypes in EC, and identify one distinct subgroup within NSMP with unfavourable outcome.
- Amirali Darbandsari
- , Hossein Farahani
- & Ali Bashashati
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Article
| Open AccessLight-evoked deformations in rod photoreceptors, pigment epithelium and subretinal space revealed by prolonged and multilayered optoretinography
Optoretinography-based detection of phototransduction and cell deformations in the retina has been mostly centered on photoreceptors. Here, the authors use prolonged and multilayered optoretinography to study light-evoked deformations in rod photoreceptors, retinal pigment epithelium, and subretinal space.
- Bingyao Tan
- , Huakun Li
- & Tong Ling
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Article
| Open AccessThe association of maternal factors with the neonatal microbiota and health
How maternal factors influence a newborn’s microbiota remains unclear. Here, the authors examined the buccal, rectal, and stool microbiotas of newborns within three days of birth and explore the impact of over 200 maternal factors on the newborns’ microbiotas.
- Bin Zhu
- , David J. Edwards
- & Gregory A. Buck
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Article
| Open AccessEvolution of retinal degeneration and prediction of disease activity in relapsing and progressive multiple sclerosis
The prognostic value of OCT in progressive vs relapsing multiple sclerosis (MS) is not clear. Analyzing 2651 OCTs of 407 MS patients, OCT predicted activity in all MS subtypes cross sectionally but longitudinal changes were not predictive in a multicenter setting.
- Julia Krämer
- , Carolin Balloff
- & Philipp Albrecht
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Article
| Open AccessDigital telomere measurement by long-read sequencing distinguishes healthy aging from disease
Here, the authors present digital telomere measurement, a high-throughput, quantitative approach for measuring full-length telomeres from long-read sequencing data at chromosome and base pair resolution. This digital telomere measurement can distinguish healthy aging from genetic telomere phenotypes.
- Santiago E. Sanchez
- , Yuchao Gu
- & Steven E. Artandi