Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy.

Background: The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.

Methods: We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.

Identification of a novel first-generation HIV-1 circulating recombinant form (CRF152_DG) among people living with HIV in Karachi, Pakistan.

Unlabelled: The objective of this study was to characterize a novel circulating recombinant form of human immunodeficiency virus type 1 (HIV-1) among people living with HIV in Karachi, Pakistan. We conducted near-full-length genome (NFLG) sequencing on eight samples exhibiting D/G recombination signals in the gene region. We successfully obtained NFLG sequences (790-9,614; with reference to the HXB2 genome) from four of the eight samples and then conducted phylogenetic and recombination analyses on them.

Evaluation of ATN Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease.

Background And Objectives: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ), phosphorylated tau 181 (p-tau), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ.

Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial.

INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations.

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

Background: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear.

Objective: To report COVID-19 rates in pwMS according to vaccine serology.

Methods: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included.

Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity.

Chronic activation of inflammatory pathways and suppressed interferon are hallmarks of immunosuppressive tumors. Previous studies have shown that CD11b integrin agonists could enhance anti-tumor immunity through myeloid reprograming, but the underlying mechanisms remain unclear. Herein we find that CD11b agonists alter tumor-associated macrophage (TAM) phenotypes by repressing NF-κB signaling and activating interferon gene expression simultaneously.

Germline Mutations in and Protection against Liver Disease.

Background: Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets.

Methods: We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations.

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

Background: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.

Methods: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.

Characterization of transcriptome diversity and in vitro behavior of primary human high-risk breast cells.

Biology and transcriptomes of non-cancerous human mammary epithelial cells at risk for breast cancer development were explored following primary isolation utilizing conditional reprogramming cell technology from mastectomy tissue ipsilateral to invasive breast cancer. Cultures demonstrated consistent categorizable behaviors. Relative viability and mammosphere formation differed between samples but were stable across three different mammary-specific media.

Variants in ADD1 cause intellectual disability, corpus callosum dysgenesis, and ventriculomegaly in humans.

Purpose: Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown.

Methods: We used exome sequencing to uncover ADD1 variants associated with intellectual disability (ID) and brain malformations.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19.

Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR).

Methods: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period).

Intussusception after Rotavirus Vaccine Introduction in India.

Background: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries.

Denigrins and Dactylpyrroles, Arylpyrrole Alkaloids from a sp. Marine Sponge.

Seven new arylpyrrole alkaloids (-), along with four known compounds, were isolated from an extract of a sp. nov. marine sponge, and their structures were elucidated by interpretation of NMR and MS spectroscopic data.

MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk.

A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.

2019 Practice guidelines for thyroid core needle biopsy: a report of the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association.

Ultrasound-guided core needle biopsy (CNB) has been increasingly used for the pre-operative diagnosis of thyroid nodules. Since the Korean Society of the Thyroid Radiology published the 'Consensus Statement and Recommendations for Thyroid CNB' in 2017 and the Korean Endocrine Pathology Thyroid CNB Study Group published 'Pathology Reporting of Thyroid Core Needle Biopsy' in 2015, advances have occurred rapidly not only in the management guidelines for thyroid nodules but also in the diagnostic terminology and classification schemes. The Clinical Practice Guidelines Development Committee of the Korean Thyroid Association (KTA) reviewed publications on thyroid CNB from 1995 to September 2019 and updated the recommendations and statements for the diagnosis and management of thyroid nodules using CNB.

Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.

Introduction: Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals.

Methods: Ninety-six cognitively normal elderly individuals underwent MRI, [ F]AZD4694 β-amyloid-PET, and [ F]MK6240 tau-PET.

Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.

To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5), or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN).

US Fine-Needle Aspiration Biopsy for Thyroid Malignancy: Diagnostic Performance of Seven Society Guidelines Applied to 2000 Thyroid Nodules.

Purpose To compare the diagnostic performance of ultrasonography (US)-based fine-needle aspiration biopsy (FNAB) criteria from seven international societies in the detection of thyroid malignancy. Materials and Methods This study included a total of 2000 consecutive thyroid nodules (≥1 cm) in 1802 patients with final diagnoses from January 2010 to May 2011. US features of the thyroid nodules were retrospectively reviewed and were classified according to the categories defined by the seven international society guidelines.

Dynamic and coordinated single-molecular interactions at TM4SF5-enriched microdomains guide invasive behaviors in 2- and 3-dimensional environments.

Membrane proteins sense extracellular cues and transduce intracellular signaling to coordinate directionality and speed during cellular migration. They are often localized to specific regions, as with lipid rafts or tetraspanin-enriched microdomains; however, the dynamic interactions of tetraspanins with diverse receptors within tetraspanin-enriched microdomains on cellular surfaces remain largely unexplored. Here, we investigated effects of tetraspan(in) TM4SF5 (transmembrane 4 L6 family member 5)-enriched microdomains (TERMs) on the directionality of cell migration.

Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters.

Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine's antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition.