Harperkirk8603

Acinetobacter baumannii encodes all enzymes required in the tricarboxylic acid (TCA) cycle and glyoxylate bypass except for isocitrate dehydrogenase kinase/phosphatase (IDHKP), which can phosphorylate isocitrate dehydrogenase (IDH) at a substrate-binding Ser site and control the carbon flux in enterobacteria, such as Escherichia coli. The potential kinase was not successfully pulled down from A. Birabresib order baumannii cell lyase; therefore, whether the IDH 1 from A. baumannii (AbIDH1) can be phosphorylated to regulate intracellular carbon flux has not been clarified. Herein, the AbIDH1 gene was cloned, the encoded protein was expressed and purified to homogeneity, and phosphorylation and enzyme kinetics were evaluated in vitro. Gel filtration and SDS-PAGE analyses showed that AbIDH1 is an 83.5 kDa homodimer in solution. The kinetics showed that AbIDH1 is a fully active NADP-dependent enzyme. The Michaelis constant Km is 46.6 (Mn2+) and 18.1 μM (Mg2+) for NADP+ and 50.5 (Mn2+) and 65.4 μM (Mg2+) for the substrate isocitrate. Phosphorylation experiments in vitro indicated that AbIDH1 is a substrate for E. coli IDHKP. The activity of AbIDH1 treated with E. coli IDHKP immediately decreased by 80% within 9 min. Mass spectrometry indicated that the conserved Ser113 of AbIDH1 is phosphorylated. Continuous phosphorylation-mimicking mutants (Ser113Glu and Ser113Asp) lack almost all enzymatic activity. Side-chain mutations at Ser113 (Ser113Thr, Ser113Ala, Ser113Gly and Ser113Tyr) remarkably reduce the enzymatic activity. Understanding the potential of AbIDH1 phosphorylation enables further investigations of the AbIDH1 physiological functions in A. baumannii.Widespread adoption of electronic health records (EHRs) has fueled the development of using machine learning to build prediction models for various clinical outcomes. However, this process is often constrained by having a relatively small number of patient records for training the model. We demonstrate that using patient representation schemes inspired from techniques in natural language processing can increase the accuracy of clinical prediction models by transferring information learned from the entire patient population to the task of training a specific model, where only a subset of the population is relevant. Such patient representation schemes enable a 3.5% mean improvement in AUROC on five prediction tasks compared to standard baselines, with the average improvement rising to 19% when only a small number of patient records are available for training the clinical prediction model.Social determinants of health (SDOH) affect health outcomes, and knowledge of SDOH can inform clinical decision-making. Automatically extracting SDOH information from clinical text requires data-driven information extraction models trained on annotated corpora that are heterogeneous and frequently include critical SDOH. This work presents a new corpus with SDOH annotations, a novel active learning framework, and the first extraction results on the new corpus. The Social History Annotation Corpus (SHAC) includes 4480 social history sections with detailed annotation for 12 SDOH characterizing the status, extent, and temporal information of 18K distinct events. We introduce a novel active learning framework that selects samples for annotation using a surrogate text classification task as a proxy for a more complex event extraction task. The active learning framework successfully increases the frequency of health risk factors and improves automatic extraction of these events over undirected annotation. An event extraction model trained on SHAC achieves high extraction performance for substance use status (0.82-0.93 F1), employment status (0.81-0.86 F1), and living status type (0.81-0.93 F1) on data from three institutions.The ability to selectively attend to a speech signal amid competing sounds is a significant challenge, especially for listeners trying to comprehend non-native speech. Attention is critical to direct neural processing resources to the most essential information. Here, neural tracking of the speech envelope of an English story narrative and cortical auditory evoked potentials (CAEPs) to non-speech stimuli were simultaneously assayed in native and non-native listeners of English. Although native listeners exhibited higher narrative comprehension accuracy, non-native listeners exhibited enhanced neural tracking of the speech envelope and heightened CAEP magnitudes. These results support an emerging view that although attention to a target speech signal enhances neural tracking of the speech envelope, this mechanism itself may not confer speech comprehension advantages. Our findings suggest that non-native listeners may engage neural attentional processes that enhance low-level acoustic features, regardless if the target signal contains speech or non-speech information.There is a lack of population based studies of autoimmune encephalitis (AE) in Latin American countries, especially in Colombia. The aim of this study is to characterize patients with AE managed in three centers in Bogotá-Colombia, emphasizing on antibody profile. We conducted a retrospective case-series study, including 9 patients. The most prevalent antibody found was NMDAR, followed by LGI1. Some distinguishing features included faciobrachial dystonia and hyponatremia in LGI1, a younger age and good outcome in NMDAR, a notable response to steroids in anti TPO-Thyroglobulin, a cerebellar syndrome associated with Anti-Yo, and epilepsy with insomnia in CASPR2.

Cocaine use disorder is an unrelenting public health concern. Despite nearly four decades of research, an FDA approved medication is not yet available.

The objective of this human laboratory study was to demonstrate the initial efficacy, safety and tolerability of topiramate-phentermine combinations for cocaine use disorder.

Thirty-one (31) participants with cocaine use disorder completed this mixed-model inpatient laboratory study. Participants were maintained on topiramate (0 [N = 11], 50 [N = 9] or 100 [N = 11] mg/day). Each topiramate group was concurrently maintained on phentermine (0, 15, 30 mg). Drug self-administration, subjective responses and cardiovascular effects following acute doses of intranasal cocaine (0, 40, 80 mg) were determined during separate experimental sessions after at least seven (7) days of maintenance on each condition.

The three groups of participants were well matched demographically and generally did not differ significantly in their responses to a range of doses of intranasal cocaine (0, 10, 20, 40, 80 mg) during a medical safety session.