Although the LiCoO (LCO) cathode material has been widely used in commercial lithium ion batteries (LIB) and shows high stability, LIB's improvements have several challenges that still need to be overcome. In this paper, we have studied the in-operando structural properties of LCO within battery cells using Bragg Coherent X-ray Diffraction Imaging to identify ways to optimise the LCO batteries' cycling. We have successfully reconstructed the X-ray scattering phase variation (a fingerprint of atomic displacement) within a ≈ (1.
View Article and Find Full Text PDFThe three-dimensional domain structure of ferroelectric materials significantly influences their properties. The ferroelectric domain structure of improper multiferroics, such as YMnO, is driven by a non-ferroelectric order parameter, leading to unique hexagonal vortex patterns and topologically protected domain walls. Characterizing the three-dimensional structure of these domains and domain walls has been elusive, however, due to a lack of suitable imaging techniques.
View Article and Find Full Text PDFBackground: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms.
View Article and Find Full Text PDFReports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.
View Article and Find Full Text PDFEvidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 (BNT162b2) and these patient-reported outcomes (PROs).
View Article and Find Full Text PDFCOVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January-30 April 2022.
View Article and Find Full Text PDFBackground: The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care.
Aim: To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services.
Method: We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Māori mental health workers on issues relating to ketamine treatment.
Background And Objectives: The gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic gene variants.
View Article and Find Full Text PDFRAS-MAPK signalling is fundamental for cell proliferation and is altered in most human cancers. However, our mechanistic understanding of how RAS signals through RAF is still incomplete. Although studies revealed snapshots for autoinhibited and active RAF-MEK1-14-3-3 complexes, the intermediate steps that lead to RAF activation remain unclear.
View Article and Find Full Text PDFBackground: Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs).
Methods: We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs.
Senexins are potent and selective quinazoline inhibitors of CDK8/19 Mediator kinases. To improve their potency and metabolic stability, quinoline-based derivatives were designed through a structure-guided strategy based on the simulated drug-target docking model of Senexin A and Senexin B. A library of quinoline-Senexin derivatives was synthesized to explore the structure-activity relationship (SAR).
View Article and Find Full Text PDFBackground: Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (β) gene.
Methods: In this open-label, phase 3 study, we evaluated the efficacy and safety of beti-cel in adult and pediatric patients with transfusion-dependent β-thalassemia and a non-β/β genotype. Patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously.
Background: The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults.
Methods: We investigated SARS-CoV-2 infections among U.S.
Histone H3 lysine 4 methylation (H3K4me) is extensively regulated by numerous writer and eraser enzymes in mammals. Nine H3K4me enzymes are associated with neurodevelopmental disorders to date, indicating their important roles in the brain. However, interplay among H3K4me enzymes during brain development remains largely unknown.
View Article and Find Full Text PDFCell-based assays for CDK8/19 inhibition are not easily defined, since there are no known cellular functions unique to these kinases. To solve this problem, we generated derivatives of 293 cells with CRISPR knockout of one or both of CDK8 and CDK19. Double knockout (dKO) of CDK8 and CDK19 together (but not individually) decreased the induction of transcription by NFκB (a CDK8/19-potentiated transcription factor) and abrogated the effect of CDK8/19 inhibitors on such induction.
View Article and Find Full Text PDFBackground and Purpose- Stroke is a risk factor for subsequent osteoporosis and fractures. We sought to understand current rates and predictors of screening and treatment for bone loss after stroke. Methods- Using the Ontario Stroke Registry from July 1, 2003 to March 31, 2013, we identified patients ≥65 years who were seen in the emergency department or hospitalized with stroke at 11 regional stroke centers in Ontario, Canada and discharged alive.
View Article and Find Full Text PDFThe identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2017
The nuclear factor-κB (NFκB) family of transcription factors has been implicated in inflammatory disorders, viral infections, and cancer. Most of the drugs that inhibit NFκB show significant side effects, possibly due to sustained NFκB suppression. Drugs affecting induced, but not basal, NFκB activity may have the potential to provide therapeutic benefit without associated toxicity.
View Article and Find Full Text PDFRationale: In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial insulin sensitivity on NO availability is unclear.
View Article and Find Full Text PDFElectron transfer rates in a series of oxo-centered triruthenium clusters featuring an extended aromatic ancillary ligand of the type [Ru3(OAc)6(μ3-O)(CO)(L)(pep)], where L = 4-cyanopyridine (cpy), pyridine (py), or 4-(dimethylamino)pyridine (dmap) and pep = 4-(phenylethynyl)pyridine were investigated. The electron self-exchange rate constants for the 0/- couple were determined by (1)H NMR line broadening experiments and found to range from 4.3 to 9.
View Article and Find Full Text PDFMajor depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission.
View Article and Find Full Text PDFJ Trauma Acute Care Surg
April 2015
Background: Following a major burn, skeletal muscle protein synthesis rate increases but is often insufficient to compensate for massively elevated muscle protein breakdown rates. Given the long-term nature of the pathophysiologic response to burn injury, we hypothesized that muscle protein synthesis rate would be chronically elevated in severely burned children. The objectives of this study were to characterize muscle protein synthesis rate of burned children over a period of 24 months after injury and to identify predictors that influence this response.
View Article and Find Full Text PDFObjective: The present study assessed the impact of the 2009 food packages mandated by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) on dietary intake and home food availability in low-income African-American and Hispanic parent/child dyads.
Design: A natural experiment was conducted to assess if the revised WIC food package altered dietary intake, home food availability, weight and various lifestyle measures immediately (6 months) following policy implementation.
Setting: Twelve WIC clinics in Chicago, IL, USA.