Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients

Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a second-generation BTK inhibitor with greater BTK selectivity. This analysis characterizes pooled CV adverse events (AE) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (clinicaltrials gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02029443","term_id":"NCT02029443"}}NCT02029443, {"type":"clinical-trial","attrs":{"text":"NCT02475681","term_id":"NCT02475681"}}NCT02475681, {"type":"clinical-trial","attrs":{"text":"NCT02970318","term_id":"NCT02970318"}}NCT02970318 and {"type":"clinical-trial","attrs":{"text":"NCT02337829","term_id":"NCT02337829"}}NCT02337829). Acalabrutinib was given orally at total daily doses of 100–400 mg, later switched to 100 mg twice daily, and continued until disease progression or toxicity. Data from 762 patients (median age: 67 years [range, 32–89]; median follow-up: 25.9 months [range, 0–58.5]) were analyzed. Cardiac AE of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in seven patients (1%). The most common any-grade cardiac AE were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AE had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, seven (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AE were reported in 67 patients (9%), 43 (64%) of whom had a preexisting history of hypertension; no patients discontinued treatment due to hypertension. No sudden cardiac deaths were reported. Overall, these data demonstrate a low incidence of new-onset cardiac AE with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with high-risk CLL (clinicaltrials gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02477696","term_id":"NCT02477696"}}NCT02477696) prospectively assess differences in CV toxicity between the two agents.     

Elastic Moduli of Non-Chiral Singe-Walled Silicon Carbide Nanotubes: Numerical Simulation Study

Silicon carbide nanotubes (SiCNTs) have generated significant research interest due to their potential use in the fabrication of electronic and optoelectronic nanodevices and biosensors. The exceptional chemical, electrical and thermal properties of SiCNTs are beneficial for their application in high-temperature and harsh-environments. In view of the limited thermal stability of carbon nanotubes, they can be replaced by silicon carbide nanotubes in reinforced composites, developed for operations at high temperatures. However, fundamentally theoretical studies of the mechanical properties of the silicon carbide nanotubes are at an early stage and their results are still insufficient for designing and exploiting appropriate nanodevices based on SiCNTs and reinforced composites. In this context, the present study deals with the determination of Young’s and shear moduli of non-chiral single-walled silicon carbide nanotubes, using a three-dimensional finite element model.     

VOx Phase Mixture of Reduced Single Crystalline V2O5: VO2 Resistive Switching

The strongly correlated electron material, vanadium dioxide (VO2), has seen considerable attention and research application in metal-oxide electronics due to its metal-to-insulator transition close to room temperature. Vacuum annealing a V2O5(010) single crystal results in Wadsley phases (VnO2n+1, n > 1) and VO2. The resistance changes by a factor of 20 at 342 K, corresponding to the metal-to-insulator phase transition of VO2. Macroscopic voltage-current measurements with a probe separation on the millimetre scale result in Joule heating-induced resistive switching at extremely low voltages of under a volt. This can reduce the hysteresis and facilitate low temperature operation of VO2 devices, of potential benefit for switching speed and device stability. This is correlated to the low resistance of the system at temperatures below the transition. High-resolution transmission electron microscopy measurements reveal a complex structural relationship between V2O5, VO2 and V6O13 crystallites. Percolation paths incorporating both VO2 and metallic V6O13 are revealed, which can reduce the resistance below the transition and result in exceptionally low voltage resistive switching.     

SnS2 Nanosheets as a Template for 2D SnO2 Sensitive Material: Nanostructure and Surface Composition Effects

Two-dimensional nanosheets of semiconductor metal oxides are considered as promising for use in gas sensors, because of the combination of a large surface-area, high thermal stability and high sensitivity, due to the chemisorption mechanism of gas detection. In this work, 2D SnO₂ nanosheets were synthesized via the oxidation of template SnS₂ nanosheets obtained by surfactant-assisted one-pot solution synthesis. The 2D SnO₂ was characterized using transmission and scanning electron microscopy (TEM, SEM), X-ray diffraction (XRD), low-temperature nitrogen adsorption, X-ray photoelectron spectroscopy (XPS) and IR spectroscopy. The sensor characteristics were studied when detecting model gases CO and NH₃ in dry (RH₂₅ = 0%) and humid (RH₂₅ = 30%) air. The combination of high specific-surface-area and increased surface acidity caused by the presence of residual sulfate anions provides a high 2D SnO₂ sensor’s signal towards NH₃ at a low temperature of 200 °C in dry air, but at the same time causes an inversion of the sensor response when detecting NH₃ in a humid atmosphere. To reveal the processes responsible for sensor-response inversion, the interaction of 2D SnO₂ with ammonia was investigated using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) in dry and humid air at temperatures corresponding to the maximum “positive” and maximum “negative” sensor response.     

Amyloid accumulation is a late event in sporadic Alzheimer's disease-like pathology in nontransgenic rats

The amyloid cascade hypothesis posits that deposition of the amyloid β (Aβ) peptide in the brain is a key event in the initiation of Alzheimer''s disease (AD). Nonetheless, it now seems increasingly unlikely that amyloid toxicity is the cause of sporadic AD, which leads to cognitive decline. Here, using accelerated-senescence nontransgenic OXYS rats, we confirmed that aggregation of Aβ is a later event in AD-like pathology. We showed that an age-dependent increase in the levels of Aβ_1–42 and extracellular Aβ deposits in the brain of OXYS rats occur later than do synaptic losses, neuronal cell death, mitochondrial structural abnormalities, and hyperphosphorylation of the tau protein. We identified the variants of the genes that are strongly associated with the risk of either late-onset or early-onset AD, including App, Apoe4, Bace1, Psen1, Psen2, and Picalm. We found that in OXYS rats nonsynonymous SNPs were located only in the genes Casp3 and Sorl1. Thus, we present proof that OXYS rats may be a model of sporadic AD. It is possible that multiple age-associated pathological processes may precede the toxic amyloid accumulation, which in turn triggers the final stage of the sporadic form of AD and becomes a hallmark event of the disease.     

Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High‐Risk Patients

Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high‐risk patients, and therefore, merits further testing in a clinical trial.     

TREC/KREC levels in children with ataxia-telangiectasia

Immunologic Research - The aim of the study was to determine the TREC/KREC levels in the patients diagnosed with ataxia-telangiectasia (AT) and to establish their informative value for early...     

Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: An international observational study

BackgroundThe presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.MethodsCases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.ResultsData on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6–15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79–104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease.ConclusionsSARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.