Double Sequential

The design and orderly layered co-immobilization of multiple enzymes on resin particles remain challenging. Herein, the SpyTag/SpyCatcher binding pair was fused to the N-terminus of an alcohol dehydrogenase (ADH) and an aldo-keto reductase (AKR), respectively. A non-canonical amino acid (ncAA), i.e. p-azido-L-phenylalanine (p-AzF), as the anchor for covalent bonding enzymes, was genetically inserted into pre-selected sites in the AKR and ADH. Employing the two bioorthogonal counterparts of SpyTag/SpyCatcher and azido-alkynyl for the immobilization of AKR and ADH enabled the sequential dual-enzyme coating on porous microspheres...

Exercise is known to benefit motor skill learning in health and neurological disease. Evidence from brain stimulation, genotyping, and Parkinson's disease studies converge to suggest that the dopamine D2 receptor, and shifts in the cortical excitation and inhibition (E:I) balance, are prime candidates for the drivers of exercise-enhanced motor learning. However, causal evidence using experimental pharmacological challenge is lacking. We hypothesised that the modulatory effect of the dopamine D2 receptor on exercise-induced changes in the E:I balance would determine the magnitude of motor skill acquisition...

BACKGROUND: Prolonged labor is a common condition associated with maternal and perinatal complications. The standard treatment with oxytocin for augmentation of labor increases the risk of adverse outcomes. Hyoscine butylbromide is a spasmolytic drug with few side effects shown to shorten labor when used in a general population of laboring women. However, research on its effect on preventing prolonged labor is lacking. We aimed to assess the effect of hyoscine butylbromide on the duration of labor in nulliparous women showing early signs of slow labor...

This randomized, double-blind, placebo-controlled phase 1/2 trial aimed at evaluating the safety and immunogenicity of Ad5-nCoV via aerosolized or intramuscular or intramuscular-aerosolized routes in SARS-CoV-2-negative adults aged over 18 years. In the phase 1 trial, participants were sequentially enrolled into one of five regimen cohorts: Low-Dose (two doses of aerosolized Ad5-nCoV with 0.5 × 1010 viral particles [vps] per dose), Middle-Dose (two doses of aerosolized Ad5-nCoV with 1.0 × 1010 vps per dose), High-Dose (two doses of aerosolized Ad5-nCoV with 2...

Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-centre investigation on the cognitive functioning of healthy human volunteers aged 50 and above with a familial predisposition to dementia...

This study investigated the impact of basketball-induced fatigue on 3-point jump shooting accuracy, the ball's entry angle (EA) into the hoop, shot release time (RT), their relationship with player positions in high-level basketball, and the correlation between cardiorespiratory fitness markers and potential shooting performance changes. Guards (n = 13), forwards (n = 13), and centers (n = 12) underwent physiological assessments. Sequentially, they performed 15 jump shots (PRE), a basketball exercise simulation (BEST) involving 24 × 30 s circuit activities, and a repeated shooting test (POST)...

In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 to form the OCCM complex. Sequentially, a second Cdt1-bound hexamer of MCM2-7 is recruited by ORC-Cdc6 to form an MCM double hexamer, which forms a part of the pre-RC. Although the mechanism of ORC binding to DNA varies across eukaryotes, how ORC is recruited to replication origins in human cells remains an area of intense investigation...

BACKGROUND: Propionic acid fermentation from renewable feedstock suffers from low volumetric productivity and final product concentration, which limits the industrial feasibility of the microbial route. High cell density fermentation techniques overcome these limitations. Here, propionic acid (PA) production from glucose and a crude glycerol/glucose mixture was evaluated using Acidipropionibacterium acidipropionici, in high cell density (HCD) batch fermentations with cell recycle. The agro-industrial by-product, heat-treated potato juice, was used as N-source...

BACKGROUND: Reinforcement learning (RL) holds great promise for intensive care medicine given the abundant availability of data and frequent sequential decision-making. But despite the emergence of promising algorithms, RL driven bedside clinical decision support is still far from reality. Major challenges include trust and safety. To help address these issues, we introduce cross off-policy evaluation and policy restriction and show how detailed policy analysis may increase clinical interpretability...

BACKGROUND: The DOSE VF randomized controlled trial (RCT) employed a pragmatic definition of refractory ventricular fibrillation (VF after three successive shocks). However, it remains unclear whether the underlying rhythm during the first three shocks was shock-refractory or recurrent VF. OBJECTIVE: To explore the relationship between alternate defibrillation strategies employed during the DOSE VF RCT and the type of VF, either shock-refractory VF or recurrent VF, on patient outcomes...

Following the 2020 COVID-19 pandemic national lockdown in South Africa, the University of the Free State launched various support initiatives for academic staff and students. Teaching and learning activities and assessments were adapted for emergency remote teaching. Students and academic staff members experienced disruption due to the migration to the online environment. This study aimed to investigate the experiences of academic staff members in an undergraduate medical programme using a mixed-methods approach in the form of a sequential exploratory design in two phases...

OBJECTIVE: The effect of one-inflow and two-inflow coronary surgical revascularization techniques inclosing skeletonized double mammary artery (BIMA) as T-graft on outcome is studied. METHODS: Early ad mid-term outcome of complete BIMA revascularization (C-T-BIMA) versus left-sided BIMA with right-sided aorto-coronary bypass (L-T-BIMA + R-CABG) is quantified and analyzed by multivariate logistic regression, Cox-regression, and Kaplan-Meier analysis in a series of 204 consecutive patients treated for triple-vessel coronary disease (3v-CAD)...

INTRODUCTION: The Baveno VI criteria have set the stage for noninvasive assessment of compensated advanced chronic liver disease (ACLD). The algorithm combining liver stiffness measurement (LSM, <20 kPa) and platelet count (>150,000/μL) safely avoids screening endoscopy for varices needing treatment (VNT) but identifies only a relatively low number of patients. We aimed to evaluate the value of spleen stiffness measurement (SSM) using spleen-dedicated elastography in ruling out VNT...

In order to overcome the problem that traditional W1 /O/W2 double emulsions do not have targeted release performance, thereby better meeting the health needs of consumers, ovalbumin fibrils/pectin-based bilayer-stabilized double emulsion (OP-BDE) co-encapsulated with Lactobacillus plantarum and curcumin was constructed with pectin as the outer protective shell, which was expected to be used in the development of novel functional foods. The effects of pectin coating on the viability of Lactobacillus plantarum under conditions including storage, pasteurization, freeze-thaw cycles and in vitro simulated digestion were investigated...

Double allylic substitution is an attractive approach to building molecular complexity from simple starting materials by creating two new bonds in one pot. However, this type of reaction has been doomed by chemoselectivity and regioselectivity issues. In this letter, we describe a new approach to introduce a-la-carte two new C-C, C-N, C-O, or C-S bonds in a chemo- and regioselective fashion. The reaction relies on sequential dual catalysis with a Lewis acid and palladium. The scope is remarkably broad, and the reaction can be diastereoselective by using secondary alcohols as the first nucleophile...

The type IB topoisomerase of budding yeast (yTop1) generates small deletions in tandem repeats through a sequential cleavage mechanism and larger deletions with random endpoints through the nonhomologous end-joining (NHEJ) pathway. Vaccinia virus Top1 (vTop1) is a minimized version of the eukaryal TopIB enzymes and uniquely has a strong consensus cleavage sequence: the pentanucleotide (T/C)CCTTp↓. To define the relationship between the position of TopIB cleavage and mutagenic outcomes, we expressed vTop1 in yeast top1Δ strains containing reporter constructs with a single CCCTT site, tandem CCCTT sites, or CCCTT sites separated by 42 bp...

BACKGROUND AND OBJECTIVE: With the emergence of immunotherapy and targeted therapies, there are more options for the perioperative period management of muscle-invasive bladder cancer (MIBC), and various types of clinical studies are emerging, leading to the need to explore ways to choose the optimal treatment modality. This review aims to synthesize past and present treatment modalities and to explore future trends in the perioperative period cares of MIBC for the benefit of clinical practitioners...

Coronary sinus (CS) anomalies, although infrequent, are increasingly diagnosed with advances in interventional procedures and imaging techniques. Most cases are asymptomatic and incidentally diagnosed. We present a case of an elderly male without comorbidities who presented with acute angina. Coronary catheterisation revealed a double-vessel disease, but incidentally, sequential angiograms captured contrast filling in the levophase of CS, revealing a giant CS. Primary percutaneous angioplasty of the right coronary artery was performed successfully...

Background In the realm of surgical and postoperative care, the application of wound dressings is a standard practice to facilitate healing, minimize infection risks, and offer a protective barrier against pathogens for optimal recovery. For instance, Theruptor is an active advanced wound care product with patented microbicidal technology. In the present study, we conducted a randomized clinical trial to compare the clinical efficacy and safety of Healthium Theruptor, 3M Tegaderm, and plain gauze dressings in patients undergoing abdominal and joint surgeries...

Proximity and feature similarity are two important determinants of perceptual grouping in vision. When viewing visual scenes conveying both grouping options simultaneously, people most usually detect proximity groups faster than similarity groups. This article demonstrates that perceptual judgments of grouping orientation guided by either proximity or contrast similarity are indicative of a sequential organization of grouping operations in the visual pathway, which lends a temporal processing advantage to proximity grouping (Experiment 1)...