Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy.

Background: Cerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.

Methods: In a phase 2-3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI).

Antitrypanosomal and antileishmanial activity of compounds from some Nigerian plants.

Ten compounds, six extracts and five fractions obtained from three Nigerian plants were assayed for their in vitro antitrypanosomal and antileishmanial activities. Each plant was extacted with hexane, ethyl acetate, and methanol. Isolated compounds were characterized and identified based on their NMR chemical shifts and comparison to literature reports.

Deconstructing inflammatory memory across tissue set points using cell circuit motifs.

Tissue ecosystems are cellular communities that maintain set points through a network of intercellular interactions. We position health and chronic inflammatory disease as alternative stable set points that are (1) robust to perturbation and (2) capable of adaptation and memory. Inflammatory memory, which is the storage of prior experience to durably influence future responsiveness, is central to how tissue ecosystems may be pushed past tipping points that stabilize disease over health.

Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study.

Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC).

Intraindividual Comparison of Ultrahigh-Spatial-Resolution Photon-Counting Detector CT and Energy-Integrating Detector CT for Coronary Stenosis Measurement.

Background: A recent simulation study proposed that stenosis measurements on coronary computed tomography (CT) angiography are influenced by the improved spatial resolution of photon-counting detector (PCD)-CT. The aim of the current study was to evaluate the impact of ultrahigh-spatial-resolution (UHR) on coronary stenosis measurements and Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification rates in patients undergoing coronary CT angiography on both PCD-CT and energy-integrating detector (EID)-CT and to compare measurements against quantitative coronary angiography.

Methods: Patients with coronary calcification on EID-CT (collimation, 192×0.

Eu singly-doped and Eu/Sm co-doped ZnS quantum dots: structure, optical properties and energy transfer.

In this study, Eu ion singly doped and Eu/Sm ions co-doped ZnS semiconductor quantum dots (QDs) were successfully synthesized using a wet chemical method in 1-octadecene (ODE) solvent. The successful doping of Sm and Eu ions into the ZnS host lattice and the composition and valence of the elements present in the sample were confirmed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Structural and morphological studies revealed the presence of Eu-doped ZnS and Eu/Sm co-doped ZnS QDs of about 3-4 nm size with a zinc blende structure.

Designed endocytosis-inducing proteins degrade targets and amplify signals.

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras (LYTACs) and cytokine receptor-targeting chimeras (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor.

A Longitudinal Study on the Impact of Working From Home During the COVID-19 Pandemic: Self-Rated General Health, Stress, and Work-Family and Family-Work Conflict-Are There Gender and Parental Status Differences?

Objective: The aim of the study is to examine the impact of working from home during the COVID-19 pandemic on general health, stress, work-family, and family-work conflict over-time and identify differences by gender and parental status.

Methods: Trajectory analyses described outcomes over time. Multinomial logistic regression relates the effects of gender, children, and the interaction between them, on group membership based on the latent class growth analyses.

Remote proctoring in complex percutaneous coronary intervention aided by mixed reality technology.

Aims: Percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) has a lower success rate and a higher complication rate compared to PCI of non-occluded coronary arteries. Co-operation and supervision by a more experienced operator (proctoring) are associated with improved success of CTO procedures. This study aims to assess the feasibility of remote proctoring using web-based communication and mixed reality technology in CTO procedures.

Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.

Sensing data and methodology from the Adaptive DBS Algorithm for Personalized Therapy in Parkinson's Disease (ADAPT-PD) clinical trial.

Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson's Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic Percept PC neurostimulator.

Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.

Background And Objectives: Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau), atrophy, and cognition.

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.

Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.