Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.

Cryptococcal meningitis is a high-mortality infection. Adding 5-fluorocytosine (5-FC) to its treatment improves outcomes, but resistance to 5-FC presents a significant challenge. We conducted whole-genome sequencing on seven C.

Effects of a cannabidiol/terpene formulation on sleep in individuals with insomnia: a double-blind, placebo-controlled, randomized, crossover study.

Study Objectives: Cannabidiol (CBD) is increasingly used as a health supplement, though few clinical studies have demonstrated benefits. The primary objective of this study was to evaluate the effects of an oral CBD-terpene formulation on sleep physiology in individuals with insomnia.

Methods: In this double-blind, placebo-controlled, randomized clinical trial, 125 individuals with insomnia received an oral administration of CBD (300 mg) and terpenes (1 mg each of linalool, myrcene, phytol, limonene, α-terpinene, α-terpineol, α-pinene, and β-caryophyllene) for ≥ 4 days/wk over 4 weeks using a crossover design.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions.

ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone.

Advanced Hyperpolarized C Metabolic Imaging Protocol for Patients with Gliomas: A Comprehensive Multimodal MRI Approach.

This study aimed to implement a multimodal H/HP-C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-C metabolic data. A total of 100 H/HP [1-C]-pyruvate MR examinations (104 HP-C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient.

Fabrication of phosphatidylcholine-EGCG nanoparticles with sustained release in simulated gastrointestinal digestion and their transcellular permeability in a Caco-2 monolayer model.

In this study, we prepared phosphatidylcholine (PC)-EGCG complex nanoparticles (P-E NPs) by solvent reflux method. The physicochemical properties, in vitro digestion, uptake in Caco-2 cells, and bidirectional permeability of P-E NPs were systematically investigated. The constructed P-E NPs had an average particle size of 118 nm, a ζ-potential of -37.

Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting.

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies. Here, we describe CAR T cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion.

Impact of Native Language, English Proficiency, and Language Concordance on Interpersonal Care During Evaluation of Acute Coronary Syndrome.

Background: High-quality interpersonal interactions between clinicians and patients can improve communication and reduce health disparities among patients with novice English proficiency (NEP). Yet, little is known about the impact of native language, NEP, and native language concordance on patient on perceptions of interpersonal care in the emergency department (ED).

Objective: To determine the associations of native language, NEP, and native language concordance with patient perceptions of interpersonal care among patients undergoing evaluation for suspected acute coronary syndrome (ACS) in the ED.

AAST multicenter prospective analysis of prehospital tourniquet use for extremity trauma.

Background: Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date.

High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I.

Objective: We investigated the prevalence of preexisting M184V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

Design: Participant data were pooled from six clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed people with HIV.

Methods: Preexisting drug resistance was assessed by historical genotypes and/or baseline proviral DNA genotyping.

Multipeak Coercive Electric-Field-Based Multilevel Cell Nonvolatile Memory With Antiferroelectric-Ferroelectric Field-Effect Transistors (FETs).

An ultralow program/erase voltage ( |V| = 4 V) is demonstrated by using an antiferroelectric-ferroelectric field-effect transistor (AFE-FE-FET) through a multipeak coercive E -field ( E ) concept for a four-level stable state with outstanding endurance (>10 cycles) and data retention (>10 s at 65 °C). The mixture of ferroelectric (FE) and AFE domains can provide stable multistate and data storage with zero bias for multilevel cell (MLC) applications. HfZrO (HZO) with AFE-FE assembles an orthorhombic/tetragonal (o/t) phase composition and is achieved by [Zr] modulation in an HZO system.

Effects of graduated compression socks on ankle inversion proprioception of half-marathon runners at different running distances.

Objectives: To determine the effect of graduated compression socks on ankle proprioception and the relationship between fatigue and ankle proprioception measures in half-marathon runners at successive 7 km intervals during a 21-km run.

Design: Repeated measures study.

Methods: Twenty well-trained half-marathon runners (mean ± SD: age 38.

Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A.

Background: The goal of gene therapy for patients with hemophilia A is to safely impart long-term stable factor VIII expression that predictably ameliorates bleeding with the use of the lowest possible vector dose.

Methods: In this phase 1-2 trial, we infused an investigational adeno-associated viral (AAV) vector (SPK-8011) for hepatocyte expression of factor VIII in 18 men with hemophilia A. Four dose cohorts were enrolled; the lowest-dose cohort received a dose of 5  × 10 vector genomes (vg) per kilogram of body weight, and the highest-dose cohort received 2 × 10 vg per kilogram.

Dach1 Extends Artery Networks and Protects Against Cardiac Injury.

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Geospatial Cellular Distribution of Cancer-Associated Fibroblasts Significantly Impacts Clinical Outcomes in Metastatic Clear Cell Renal Cell Carcinoma.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment.

Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy.

Objective: To determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses.

Methods: We acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

Background: Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries.

Purpose: To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).

Data Sources: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.

Evaluating Biochemically Recurrent Prostate Cancer: Histologic Validation of F-DCFPyL PET/CT with Comparison to Multiparametric MRI.

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) may improve detection of recurrence compared with multiparametric MRI; however, histopathologic validation is lacking. Purpose To determine the sensitivity, specificity, and positive predictive value (PPV) of F-DCFPyL PET/CT based on histologic analysis and to compare with pelvic multiparametric MRI in men with biochemically recurrent prostate cancer.

Mechanism study of the air migration and flowrate distribution in an aquifer with lenses of different permeabilities during air sparging remediation.

The poor performance of air sparging (AS) remediation in heterogeneous porous media is receiving increasing attention. However, understanding of the air migration and flowrate distribution mechanisms in heterogeneous aquifers is still lacking. In this study, for experimental purposes, a heterogeneous aquifer with lenses of different permeabilities was designed in the laboratory.

Non-Traumatic Subdural Hemorrhage and Risk of Arterial Ischemic Events.

Background and Purpose- The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods- We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells.

Clinical Outcomes of 1625 Patients With Primary Aldosteronism Subtyped With Adrenal Vein Sampling.

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients.