MTT and Blood-Brain Barrier Disruption within Asymptomatic Vascular WM Lesions.

Background And Purpose: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects.

International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer.

Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data.

Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens.

Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study.

Background: Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU.

Bone Health in Pediatric Patients With Crohn Disease.

Objective: The aim of our study was to examine longitudinal changes in bone mineral density (BMD) of children and adolescents with Crohn disease (CD), and risk factors related to low BMD.

Patients And Methods: All patients ages from 2 to 18 years with CD who underwent dual-energy X-ray absorptiometry (DXA) at diagnosis and at the end of follow-up between 1999 and 2018 were considered for inclusion in this retrospective study. Factors related to changes in BMD at diagnosis and during follow-up were investigated.

Association of Ligamentous Laxity, Male Sex, Chronicity, Meniscal Injury, and Posterior Tibial Slope With a High-Grade Preoperative Pivot Shift: A Post Hoc Analysis of the STABILITY Study.

Background: A spectrum of anterolateral rotatory laxity exists in anterior cruciate ligament (ACL)-injured knees. Understanding of the factors contributing to a high-grade pivot shift continues to be refined.

Purpose: To investigate factors associated with a high-grade preoperative pivot shift and to evaluate the relationship between this condition and baseline patient-reported outcome measures (PROMs).

Paediatric patients report lower health-related quality of life in daily clinical practice compared to new normative PedsQL data.

Aim: To compare Health-Related Quality of Life (HRQOL) of paediatric patients with newly collected HRQOL data of the general Dutch population, explore responses to individual items and investigate variables associated with HRQOL.

Methods: Children (8-12y) and adolescents (13-17y) from the general population (N = 966) and from a paediatric population (N = 1209) completed the Pediatric Quality of Life Inventory (PedsQL ) online via the KLIK Patient-Reported Outcome Measures portal. PedsQL scale scores were compared between groups with independent t tests, by age group and gender.

Photoactivated nanomotors via aggregation induced emission for enhanced phototherapy.

Aggregation-induced emission (AIE) has, since its discovery, become a valuable tool in the field of nanoscience. AIEgenic molecules, which display highly stable fluorescence in an assembled state, have applications in various biomedical fields-including photodynamic therapy. Engineering structure-inherent, AIEgenic nanomaterials with motile properties is, however, still an unexplored frontier in the evolution of this potent technology.

Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure.

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, is primarily metabolized via glucuronidation by the uridine 5'-diphospho-glucuronosyltransferase (UGT) isoform UGT1A9. This noncompartmental meta-analysis of ertugliflozin pharmacokinetics evaluated the relationship between ertugliflozin exposure and dose, and the effect of UGT1A9 genotype on ertugliflozin exposure. Pharmacokinetic data from 25 phase 1 studies were pooled.

Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms).

Computationally designed pyocyanin demethylase acts synergistically with tobramycin to kill recalcitrant biofilms.

is an opportunistic human pathogen that develops difficult-to-treat biofilms in immunocompromised individuals, cystic fibrosis patients, and in chronic wounds. has an arsenal of physiological attributes that enable it to evade standard antibiotic treatments, particularly in the context of biofilms where it grows slowly and becomes tolerant to many drugs. One of its survival strategies involves the production of the redox-active phenazine, pyocyanin, which promotes biofilm development.

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

Background: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.

Methods: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.

Terpolymer-stabilized complex coacervates: A robust and versatile synthetic cell platform.

The utilization of liquid-liquid phase separated systems has seen increased attention as synthetic cell platforms due to their innate ability to sequester interesting, functional, and biologically relevant materials. However, their applications are limited by the temporal stability of such condensed phases. While there are a number of strategies toward droplet stabilization, in our group we have developed a polymer-based approach to stabilize complex coacervate microdroplets.

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10 ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1 but not KLRG1 ILC2 produced IL-10 upon activation with IL-33 and retinoic acid.

International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.

5-HT receptors expressed throughout the human body are targets for established therapeutics and various drugs in development. Their diversity of structure and function reflects the important role 5-HT receptors play in physiologic and pathophysiological processes. The present review offers a framework for the official receptor nomenclature and a detailed understanding of each of the 14 5-HT receptor subtypes, their roles in the systems of the body, and, where appropriate, the (potential) utility of therapeutics targeting these receptors.

Serial [F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer.

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16β-[F]-fluoro-5α-dihydrotestosterone positron emission tomography ([F]-FDHT-PET) can be used for noninvasive visualisation of AR. [F]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [F]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response.

Programmed spatial organization of biomacromolecules into discrete, coacervate-based protocells.

The cell cytosol is crowded with high concentrations of many different biomacromolecules, which is difficult to mimic in bottom-up synthetic cell research and limits the functionality of existing protocellular platforms. There is thus a clear need for a general, biocompatible, and accessible tool to more accurately emulate this environment. Herein, we describe the development of a discrete, membrane-bound coacervate-based protocellular platform that utilizes the well-known binding motif between Ni-nitrilotriacetic acid and His-tagged proteins to exercise a high level of control over the loading of biologically relevant macromolecules.

Association of Circulating Metabolites in Plasma or Serum and Risk of Stroke: Meta-analysis From 7 Prospective Cohorts.

Objective: To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings.

Methods: We investigated the association of metabolites with risk of stroke in 7 prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by nuclear magnetic resonance technology. The relationship between metabolites and stroke was assessed with Cox proportional hazards regression models.

Plasma Trough Concentrations of Antihypertensive Drugs for the Assessment of Treatment Adherence: A Meta-Analysis.

Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of antihypertensive medications in patients with hypertension. Trough concentrations could possibly be used as drug-specific cutoff values in the biochemical assessment of (non-)adherence. We performed a literature review and meta-analysis of pharmacokinetic studies to determine plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan.

Quantitative Susceptibility Mapping of Brain Iron and β-Amyloid in MRI and PET Relating to Cognitive Performance in Cognitively Normal Older Adults.

Background For individuals with mild cognitive impairment (MCI) or dementia, elevated brain iron together with β-amyloid is associated with lower cognitive functioning. But this needs further investigation among cognitively normal older adults. Purpose To investigate via quantitative susceptibility mapping (QSM) in MRI and PET how cerebral iron together with β-amyloid affects cognition among cognitively normal older adults.

Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis.

Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.

Insight into N-terminal localization and dynamics of engineered virus-like particles.

Virus-like particles composed of the cowpea chlorotic mottle virus (CCMV) capsid protein (CP) have been extensively studied as carrier systems in nanoscience. One well-established method to improve their stability under physiological conditions is to fuse a stimulus-responsive elastin-like polypeptide (ELP) to the N-terminus of the CPs. Even though the N-terminus should in principle be localized in the inner cavity of the protein cage, studies on the native CCMV revealed its accessibility on the particle surface.

Metabolic Age Based on the BBMRI-NL H-NMR Metabolomics Repository as Biomarker of Age-related Disease.

Background: The blood metabolome incorporates cues from the environment and the host's genetic background, potentially offering a holistic view of an individual's health status.

Methods: We have compiled a vast resource of proton nuclear magnetic resonance metabolomics and phenotypic data encompassing over 25 000 samples derived from 26 community and hospital-based cohorts.

Results: Using this resource, we constructed a metabolomics-based age predictor (metaboAge) to calculate an individual's biological age.

Association of common genetic variants with brain microbleeds: A genome-wide association study.

Objective: To identify common genetic variants associated with the presence of brain microbleeds (BMBs).

Methods: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel.

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD.