Med

PurposeSubstantial preclinical data support that fingolimod, a drug that dysregulates sphingolipid metabolism, could both prevent chemotherapy-induced neuropathy (CIPN) and treat established chemotherapy-induced neuropathy. MethodsTwo pilot-phase clinical trials were developed to evaluate whether fingolimod could 1) inhibit the development of paclitaxel-induced peripheral neuropathy and 2) diminish established CIPN in humans. ResultsUnfortunately, both clinical trials were not able to fulfill ...

One of the most intriguing characteristics of cell-free DNA (cfDNA) from plasma is the sequence at the ends of the fragments. Previous studies have shown that these end-sequences are somewhat different in cancer patients than in healthy individuals. While investigating this characteristic, we noticed that the bases at the 5-ends of a double-stranded fragment were highly correlated with the GC content of that particular fragment. This led us to develop a method, called MendSeqS (Modified End-base...

Telomeres, the repetitive DNA elements at chromosome ends, are pivotal for maintenance of genome integrity. Previous studies from our group and others have highlighted the translational potential of tissue-based telomere length measurements to address the clinical challenge of improving diagnosis, individualized risk stratification, and accurate prognostication of different diseases. Here, we describe a high-throughput method that quantitates cell type-specific telomere lengths at a single cell ...

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that urgently requires new treatments. Masitinib, a tyrosine kinase inhibitor targeting microglia and mast cells, aims to slow disease progression by reducing neuroinflammation. A previously reported phase 2b/3 study showed that masitinib (4.5 mg/kg/day) with riluzole significantly slowed decline of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) over 48 weeks in a specific patient populatio...

ObjectiveIn this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. MethodsSubjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily...

Current guidelines prioritize the use of the Azvudine in coronavirus disease 2019 (COVID-19) patients. However, the clinical effectiveness of Azvudine in real-world studies was lacking, despite the clinical trials showed shorter time of nucleic acid negative conversion. To evaluate the clinical effectiveness following Azvudine treatment in hospitalized COVID-19 patients, we identified 1505 hospitalized COVID-19 patients during the study period, with a follow-up of up to 29 days. After exclusions...

ObjectivesThe primary aim of this study is to increase our understanding of the adaptive immune response to the SARS-CoV-2 virus by assaying the peripheral immune repertoire for virus-associated T-cell receptors (TCRs). Secondary aims include identification and characterization of SARS-CoV-2-specific B-cell receptors (BCRs) and monoclonal antibodies (mAbs) generated by antibody-producing cells during and after acute infection. Trial designImmuneRACE is a prospective, single group, multi-cohort,...

Although individually uncommon, rare diseases (RD) affect an estimated 300 million people worldwide. Establishing a public health approach to RD requires counting diseases and affected patients. However, RD are under-represented in medical terminologies, with only a small fraction of RD possessing specific and unambiguous codes, and those codes not being explicitly designated as rare. To tackle the challenge of RD codification and interoperability, Orphanet has developed a nomenclature of RD th...

BackgroundFor many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Whether measuring thousands of proteins offers predictive information across a wide range of diseases is unknown. MethodsIn 41,931 individuals from the UK Biobank Pharma Proteomics Project (UKB-PPP), we integrated [~]3000 plasma proteins with clinical information to derive sparse prediction models for the 10-year incidence of 218 common and rare diseases (81 - 6038 cases). We compa...

Long-read DNA sequencing detects genetic variants and epigenetic modifications simultaneously, but optimal preservation of molecular length and base modifications typically requires cold-chain infrastructure. This infrastructure dependence restricts genomics to well-resourced laboratories and limits field research. We show that ensilication, the encapsulation of DNA within silica matrices, preserves DNA integrity at ambient temperature equivalent to -80 {degrees}C freezing. Using Genome-in-a-Bot...

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/25342726v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@8edb94org.highwire.dtl.DTLVardef@f20105org.highwire.dtl.DTLVardef@21033corg.highwire.dtl.DTLVardef@15b865e_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOVISUAL ABSTRACT:C_FLOATNO C_FIG Structured phenotypic annotations linked to genetic data can drive diagnostic insight and therapeutic discovery in complex diseases. However, poor research access to the rich ...

Background and AimsLarge population-based studies on gut microbiota and hypertension have been conducted using methods with low taxonomic resolution and office blood pressure. This study aims to investigate the relationship between specific characteristics of the gut microbiome and 24-hour blood pressure measurements. Methods and resultsThe association of gut microbial species, determined by shotgun metagenomic sequencing of fecal samples, with 24-hour ambulatory blood pressure measurements was...

Vascular graft vasospasm is a lethal risk when using grafts for revascularization and reconstructive surgery. Revascularization is a treatment modality for ischemic diseases including Moyamoya disease that requires bypass surgery. Cerebrovascular graft transplantation carries a 5-10% risk of vasospasm, which can lead to devastating neurological sequelae. Here we report clinical outcomes associated with ex vivo botulinum toxin A (BoNT/A) treatment of arterial graft and provide reverse translation...

BACKGROUNDThe microbiota has been reported to play an important role in the occurrence of brain aneurysms (CA). However, no microbiota or metabolite has been used for diagnosis or therapy of CA till now. Therefore, we investigated the shifts of gut microbiota and metabolites in CA patients, and explored the feasibility of using them as biomarkers and therapeutic targets. METHODSThe microbial DNA was extracted from the stool samples of the CA and healthy volunteer groups. The variable V3-V4 regi...

O_FIG O_LINKSMALLFIG WIDTH=153 HEIGHT=200 SRC="FIGDIR/small/23291309v1_figu1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1006b68org.highwire.dtl.DTLVardef@8b86b1org.highwire.dtl.DTLVardef@37eb77org.highwire.dtl.DTLVardef@143fac6_HPS_FORMAT_FIGEXP M_FIG C_FIG Background and PurposeWe aimed to assess sex differences in lipid metabolism disorders in patients with BPA-related intracerebral hemorrhage, as well as changes in {beta}3-adrenoceptors and oxidative stress pa...

Key pointsO_LIWe report findings from a phase 2 study of MY008211A among Chinese men and women aged [≥]18 years with paroxysmal nocturnal hemoglobinuria C_LIO_LIIncreases in hemoglobin of [≥]20 g/L were maintained for up to 44 weeks of treatment with MY008211A in all 34 patientsiv C_LI Explanation of noveltyParoxysmal nocturnal hemoglobinuria is characterized by red blood cell (RBC) destruction and a prothrombotic state.v Treatments exist such as complement 5 inhibitors but these carry th...

BackgroundNeuroinflammation is thought to contribute to postoperative central nervous system (CNS)-related complications, and the apolipoprotein E (APOE)-mimetic peptide CN-105 blocks neuroinflammation in animal models. Thus, here we examined postoperative cerebrospinal fluid (CSF) proteome changes and their modulation by CN-105. ObjectiveTo evaluate postoperative changes in the CSF proteome, and their modulation by the APOE mimetic peptide CN-105. MethodsWe performed mass spectrometry-based p...

IntroductionNo conclusive evidence for a link between polyunsaturated fatty acids (PUFA) and cerebral aneurysm has been found in observational research. The aim of our study was to determine the causal impact of PUFA on cerebral aneurysm. MethodsTwo sample Mendelian randomization (MR) was performed using genetic instruments derived from a recent genome wide association study (GWAS) of fatty acids from UK Biobank and outcome data obtained from the large-scale cerebral aneurysm GWASs in European ...

IntroductionData on the correlation between SARS-CoV-2 neutralizing activity and strain-specific anti-RBD IgG antibody (anti-RBD) titers is limited, particularly in the context of XBB.1.5-adapted vaccination. MethodsA direct comparison of neutralizing activity, measured as 50% neutralization (NT50), and anti-RBD titers, measured using an ELISA, was conducted using serum samples collected in Japan before and after XBB.1.5-adapted mRNA vaccination. ResultsA total of 108 serum samples from 54 pat...

COVID-19 (coronavirus disease 2019) vaccines have been rapidly developed and deployed globally as a measure to combat the disease. These vaccines have been demonstrated to confer significant protection, but there have been reports of temporal decay in antibody titer. Furthermore, several variants have been identified with variable degrees of antibody resistance. These two factors suggest that a booster vaccination may be worthy of consideration. While such a booster dose has been studied as a se...