Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving the performance of nadolol stereoisomers' preparative separation using Chiralpak IA by SMB chromatography.

The pseudobinary preparative separation of nadolol stereoisomers is performed by simulated moving bed chromatography (SMB). Using the Chiralpak IA adsorbent, a new 25:75:0.1 (v/v/v) methanol-acetonitrile-diethylamine solvent composition was selected to perform the experimental SMB separation and compare it with the previous results obtained using pure methanol. Using a 2 g L-1 total feed concentration of an equimolar mixture of the four stereoisomers of nadolol, the more retained component was fully recovered (100% purity and 100% recovery), with a system productivity of 0.77 g L-1 hour-1 and a solvent consumption of 9.62 L g-1 . Comparing these results with the ones previously reported using 100:0.1 methanol-diethylamine solvent composition, this work shows that the 25:75:0.1 methanol-acetonitrile-diethylamine is a better alternative for the preparative separation of nadolol stereoisomers by SMB chromatography. These results are confirmed by simulation of the SMB operation for higher feed concentrations, by comparing the performances of the two solvent compositions using the data obtained experimentally through the measurement of the adsorption equilibrium isotherms and the kinetic data obtained for both solvents. The new experimental and simulation results stress out that the performance of the preparative separation can be improved by a careful selection of the solvent composition.
Identification of Plasmodium GAPDH epitopes for generation of antibodies that inhibit malaria infection

This study reports on the identification of two Plasmodium GAPDH epitope peptides that are responsible for sporozoite–Kupffer cell interaction and act as antigens against malaria infection. Plasmodium sporozoite liver infection is an essential step for parasite development in its mammalian host. Previously, we used a phage display library to identify mimotope peptides that bind to Kupffer cells and competitively inhibit sporozoite–Kupffer cell interaction. These peptides led to the identification of a Kupffer cell receptor—CD68—and a Plasmodium sporozoite ligand—GAPDH—that are required for sporozoite traversal of Kupffer cells and subsequent infection of hepatocytes. Here, we report that the C-terminal end of Plasmodium GAPDH interacts with the Kupffer CD68 receptor, and identify two epitopes within this region as candidate antigens for the development of antibodies that inhibit Plasmodium infection.
The human phosphatase CDC14A modulates primary cilium length by regulating centrosomal actin nucleation

CDC14A codes for a conserved proline‐directed phosphatase, and mutations in the gene are associated with autosomal‐recessive severe to profound deafness, due to defective kinocilia. A role of CDC14A in cilia formation has also been described in other organisms. However, how human CDC14A impacts on cilia formation remains unclear. Here, we show that human RPE1 hCDC14APD cells, encoding a phosphatase dead version of hCDC14A, have longer cilia than wild‐type cells, while hCDC14A overexpression reduces cilia formation. Phospho‐proteome analysis of ciliated RPE1 cells identified actin‐associated and microtubule binding proteins regulating cilia length as hCDC14A substrates, including the actin‐binding protein drebrin. Indeed, we find that hCDC14A counteracts the CDK5‐dependent phosphorylation of drebrin at S142 during ciliogenesis. Further, we show that drebrin and hCDC14A regulate the recruitment of the actin organizer Arp2 to centrosomes. In addition, during ciliogenesis hCDC14A also regulates endocytosis and targeting of myosin Va vesicles to the basal body in a drebrin‐independent manner, indicating that it impacts primary cilia formation in a multilayered manner.
Neuromodulation in eating disorders and obesity: a promising way of treatment?

Neuromodulation can affect the functioning of the central nervous system (CNS), and emotional/eating behavior is an exciting facet of that functioning. Therefore, it would be possible to offer an alternative (or complement) treatment to psychotropic medications and different psychological and nutritional approaches to both eating disorders (EDs) and obesity. Although there are a number of publications in these areas, a systematic review has not been conducted to date. Abstracts, letters, conference reports, dissertations, and reviews were excluded. Clinical trials and controlled human clinical trials were filtered and included in this study. Articles included were based on the population suffering from anorexia nervosa, bulimia nervosa, binge ED, overweight, and obesity. No restrictions were placed on the sample size. Only trials investigating the effect of neuromodulation by means of deep brain stimulation (DBS), transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS) were included. The following databases were used to conduct the search: MEDLINE/ PubMed, PsycINFO, PsycArticles, and Cochrane (Search Trials, CENTRAL). Study selection was performed following the PRISMA process (PRISMA 2009 Checklist). The total number of participants in all the trials was 562 (DBS, 25; tDCS, 138; TMS, 399; range, 3–90; median, 23.5). As a result, 50% of the studies had samples of between 14 and 38 participants. Neuro-modulation in ED seems to have certain clinical potential, and therefore, this is a promising area for further research. Developments in ED neuromodulation will be linked to neuroimaging to identify potential stimulation targets and possible biomarkers of treatment response. To date, TMS and/or direct current stimulation (DCS) is not the first-line treatment yet, but it could become a preferred option of treatment in the future. Further studies should avoid small sample sizes and the use of different methodologies. Currently, neuromodulation techniques are in the experimental phase, and they are not an evidence-based treatment for ED.
Insulin in the ventral tegmental area reduces cocaine‐evoked dopamine in the nucleus accumbens in vivo

Mesolimbic dopamine circuits, implicated in incentive motivation, are sensitive to changes in metabolic state such as weight loss and diet‐induced obesity. These neurons are important targets for metabolic hormones such as leptin, glucagon‐like peptide‐1, ghrelin and insulin. Insulin receptors are located on dopamine neurons in the ventral tegmental area (VTA) and we have previously demonstrated that insulin induces long‐term depression of excitatory synapses onto VTA dopamine neurons. While insulin can decrease dopamine concentration in somatodendritic regions, it can increase dopamine in striatal slices. Whether insulin directly targets the VTA to alter dopamine release in projection areas, such as the nucleus accumbens (NAc), remains unknown. The main goal of the present experiments was to examine NAc dopamine concentration following VTA administration of insulin. Using in vivo FSCV to detect rapid fluctuations in dopamine concentration, we showed that intra‐VTA insulin via action at insulin receptors reduced pedunculopontine nucleus‐evoked dopamine release in the NAc. Furthermore, intra‐VTA insulin reduced cocaine‐potentiated NAc dopamine. Finally, intra‐VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra‐VTA administered insulin receptor antagonist. Together, these data demonstrate that mesolimbic dopaminergic projections are important targets of the metabolic hormone, insulin.
Therapeutic Chemical Screen Identifies Phosphatase Inhibitors to Reconstitute PKB Phosphorylation and Cardiac Contractility in ILK-Deficient Zebrafish

Patients with inherited dilated cardiomyopathy (DCM) often suffer from severe heart failure based on impaired cardiac contractility leading to increased morbidity and mortality. Integrin-linked kinase (ILK) as a part of the cardiac mechanical stretch sensor was found to be an essential genetic regulator of cardiac contractility. Integrin-linked kinase localizes to z-disks and costameres in vertebrate hearts and regulates the activity of the signaling molecule protein kinase B (PKB/Akt) by controlling its phosphorylation. Despite identification of several potential drug targets in the ILK signaling pathway, pharmacological treatment strategies to restore contractile function in ILK-dependent cardiomyopathies have not been established yet. In recent years, the zebrafish has emerged as a valuable experimental system to model human cardiomyopathies as well as a powerful tool for the straightforward high-throughput in vivo small compound screening of therapeutically active substances. Using the ILK deficient zebrafish heart failure mutant main squeeze (msq), which shows reduced PKB phosphorylation and thereby impaired cardiac contractile force, we identified here, in an automated small compound screen, the protein phosphatase inhibitors calyculin A and okadaic acid significantly restoring myocardial contractile function by reconstituting PKB phosphorylation in msq ILK-deficient zebrafish embryos.
Dribbling speed along curved paths predicts attacking performance in match-realistic one vs. one soccer games

ABSTRACT This study assessed whether a new, closed-skill dribbling or sprinting task could predict attacking performance in soccer. Twenty-five male players were recruited from the Londrina Junior Team Football Academy in Brazil and asked to either dribble the ball or sprint through five custom circuits that varied in average curvature (0–1.37 radians.m−1). These measures were then validated using a realistic one vs. one competition in which each player acted as attacker or defender in turn (N = 1330 bouts). Sprinting (ICC = 0.96) and dribbling (ICC = 0.97) performances were highly repeatable for individual players. Average dribbling speed decreased non-linearly with increasing circuit curvature (F = 239.5; P < 0.001) from 5.19 ± 0.11 ms−1 on the straightest path to 2.13 ± 0.03 ms−1 on the curviest. Overall, dribbling but not sprinting performance predicted attacking success in the one vs. one competition, explaining more than 50% of the variation in attacking success alone (rp = 0.70; P < 0.001). In conclusion, our new closed-skill dribbling assessment is a valid and reliable protocol to predict a soccer player’s success in attacking performance in one vs. one situation, and can be used to identify talented players.
Proactive Virtual Machine Migration in Fog Environments

Fog computing provides a low latency access to resources at the edge of the network for resource-constrained devices. The high mobility of some of these devices, such as vehicles, brings great challenges related to resource allocation and management. In order to improve the management of computing resources utilized by mobile users connected to the Fog infrastructure, this paper proposes a virtual machine placement and migration decision model based on mobility prediction. Simulations have shown that moving the virtual machine to a Fog node ahead of the user’s route using the proposed approach can decrease by almost 50% the number of migrations needed by the user. The Fog architecture provides an average latency of about 15 milliseconds for the users’ applications and the proposed approach presents a lower latency compared to a greedy approach for the VM placement problem.
An Empathy-Driven, Conversational Artificial Intelligence Agent (Wysa) for Digital Mental Well-Being: Real-World Data Evaluation Mixed-Methods Study

Background A World Health Organization 2017 report stated that major depression affects almost 5% of the human population. Major depression is associated with impaired psychosocial functioning and reduced quality of life. Challenges such as shortage of mental health personnel, long waiting times, perceived stigma, and lower government spends pose barriers to the alleviation of mental health problems. Face-to-face psychotherapy alone provides only point-in-time support and cannot scale quickly enough to address this growing global public health challenge. Artificial intelligence (AI)-enabled, empathetic, and evidence-driven conversational mobile app technologies could play an active role in filling this gap by increasing adoption and enabling reach. Although such a technology can help manage these barriers, they should never replace time with a health care professional for more severe mental health problems. However, app technologies could act as a supplementary or intermediate support system. Mobile mental well-being apps need to uphold privacy and foster both short- and long-term positive outcomes. Objective This study aimed to present a preliminary real-world data evaluation of the effectiveness and engagement levels of an AI-enabled, empathetic, text-based conversational mobile mental well-being app, Wysa, on users with self-reported symptoms of depression. Methods In the study, a group of anonymous global users were observed who voluntarily installed the Wysa app, engaged in text-based messaging, and self-reported symptoms of depression using the Patient Health Questionnaire-9. On the basis of the extent of app usage on and between 2 consecutive screening time points, 2 distinct groups of users (high users and low users) emerged. The study used mixed-methods approach to evaluate the impact and engagement levels among these users. The quantitative analysis measured the app impact by comparing the average improvement in symptoms of depression between high and low users. The qualitative analysis measured the app engagement and experience by analyzing in-app user feedback and evaluated the performance of a machine learning classifier to detect user objections during conversations. Results The average mood improvement (ie, difference in pre- and post-self-reported depression scores) between the groups (ie, high vs low users; n=108 and n=21, respectively) revealed that the high users group had significantly higher average improvement (mean 5.84 [SD 6.66]) compared with the low users group (mean 3.52 [SD 6.15]); Mann-Whitney P=. 03 and with a moderate effect size of 0.63. Moreover, 67.7% of user-provided feedback responses found the app experience helpful and encouraging. Conclusions The real-world data evaluation findings on the effectiveness and engagement levels of Wysa app on users with self-reported symptoms of depression show promise. However, further work is required to validate these initial findings in much larger samples and across longer periods.
Charge transport pathways in metal porphyrin as interplay between long and short range scattering processes

We have investigated the ballistic transport for Mn, Fe–porphyrin molecules in contact with Au(111) electrodes by using density functional theory. We show that the information resulted from the projected density of electronic states does not provide a complete picture of the transport mechanism. Instead, we propose a methodology based on the concept of the orbital projected transmissions for selected groups of atoms. We have found that the transmission channels for occupied states can be assigned to short range scattering processes at gold-molecule interface, while for the states above Fermi level the transmission takes place via long range scattering processes. The interplay between these two conduction mechanisms is responsible for the transport path in metal–porphyrin; our model is in qualitative agreement with the existing experimental data on transport pathway on single porphyrin molecules.
Mathematics Anxiety: Mapping the Literature by Bibliometric Analysis

The goal of this study is to analyse the publications on mathematics anxiety to contribute to the development of the related literature. A total of 537 papers on mathematics anxiety published in various databases of Web of Science between 2000 and 2018 years were retrieved and analysed through bibliometric analysis approach. Bibliographic coupling of the source, the authors, the countries, the institutions, the publications and co-occurrences of the author keywords were analysed and visualised through VOS Viewer software. Maths anxiety has been studied frequently with the concepts of anxiety, motivation, self-efficacy, self-concept, maths performance, maths achievement, gender-related differences, test anxiety, working memory, arithmetic, mental arithmetic, and numeracy. Frontiers in Psychology and Learning and Individual Differences have been the top journals, and the University of Chicago has been the most influential institution, and the USA has had a significant prevalence in this area.
Impact of Assisted Peritoneal Dialysis Modality on Outcomes: A Cohort Study of the French Language Peritoneal Dialysis Registry

Background: Patients on peritoneal dialysis (PD) can be assisted by a nurse or a family member and treated either by automated PD (APD) or continuous ambulatory PD (CAPD). The aim of this study was to evaluate the effect of PD modality and type of assistance on the risk of transfer to haemodialysis (HD) and on the peritonitis risk in assisted PD patients. Method: This was a retrospective study based on data from the French Language PD Registry. All adults starting assisted PD in France between 2006 and 2015 were included. Events of interest were transfer to HD, peritonitis and death. Cox regression models were used for statistical analysis. Results: Among the 12,144 incident patients who started PD in France during the study period, 6,167 were assisted. There were 5,060 nurse-assisted and 1,095 family-assisted PD patients. Overall, 5,171 were treated by CAPD and 996 by APD. In multivariate analysis, CAPD, compared to APD, was not associated with the risk of transfer to HD (cause specific hazard ratios [cs-HR] 0.96 [95% CI 0.84–1.09]). Patients on nurse-assisted PD had a lower risk of transfer to HD than family assisted PD patients (cs-HR 0.85 [95% CI 0.75–0.97]). Neither PD modality nor type of assistance were associated with peritonitis risk. Conclusions: In assisted PD, technique survival was not associated with PD modality. Nurse-assisted patients had a lower risk of transfer to HD than family assisted patients. Peritonitis risk was not influenced either by PD modality, or by type of assistance. Both APD and CAPD should be offered to assisted-PD patients.
Biological Consequences of MHC-II Expression by Tumor Cells in Cancer

Immunotherapy has emerged as a key pillar of cancer treatment. To build upon the recent successes of immunotherapy, intense research efforts are aimed at a molecular understanding of antitumor immune responses, identification of biomarkers of immunotherapy response and resistance, and novel strategies to circumvent resistance. These studies are revealing new insight into the intricacies of tumor cell recognition by the immune system, in large part through MHCs. Although tumor cells widely express MHC-I, a subset of tumors originating from a variety of tissues also express MHC-II, an antigen-presenting complex traditionally associated with professional antigen-presenting cells. MHC-II is critical for antigen presentation to CD4+ T lymphocytes, whose role in antitumor immunity is becoming increasingly appreciated. Accumulating evidence demonstrates that tumor-specific MHC-II associates with favorable outcomes in patients with cancer, including those treated with immunotherapies, and with tumor rejection in murine models. Herein, we will review current research regarding tumor-enriched MHC-II expression and regulation in a range of human tumors and murine models, and the possible therapeutic applications of tumor-specific MHC-II.
Inhibition of ezrin causes PKCα-mediated internalization of erbb2/HER2 tyrosine kinase in breast cancer cells

Unlike other ErbB family members, HER2 levels are maintained on the cell surface when the receptor is activated, allowing prolonged signaling and contributing to its transforming ability. Interactions between HER2, HSP90, PMCA2, and NHERF1 within specialized plasma membrane domains contribute to the membrane retention of HER2. We hypothesized that the scaffolding protein ezrin, which has been shown to interact with NHERF1, might also help stabilize the HER2–PMCA2–NHERF1 complex at the plasma membrane. Therefore, we examined ezrin expression and its relationship with HER2, NHERF1, and PMCA2 levels in murine and human breast cancers. We also used genetic knockdown and/or pharmacologic inhibition of ezrin, HSP90, NHERF1, PMCA2, and HER2 to examine the functional relationships between these factors and membrane retention of HER2. We found ezrin to be expressed at low levels at the apical surface of normal mammary epithelial cells, but its expression is up-regulated and correlates with HER2 expression in hyperplasia and tumors in murine mammary tumor virus-Neu mice, in human HER2-positive breast cancer cell lines, and in ductal carcinoma in situ and invasive breast cancers from human patients. In breast cancer cells, ezrin co-localizes and interacts with HER2, NHERF1, PMCA2, and HSP90 in specialized membrane domains, and inhibiting ezrin disrupts interactions between HER2, PMCA2, NHERF1, and HSP90, inhibiting HER2 signaling and causing PKCα-mediated internalization and degradation of HER2. Inhibition of ezrin synergizes with lapatinib in a PKCα-dependent fashion to inhibit proliferation and promote apoptosis in HER2-positive breast cancer cells. We conclude that ezrin stabilizes a multiprotein complex that maintains active HER2 at the cell surface.
Analyzing Goals of Care in Advanced Cancer Patients and Their Family Caregivers: Evidence-based Research

Objective The study objective was to determine concordance between patients and family caregivers’ preferences for quality or length of life over time. Background Patients with advanced cancer are confronted with difficult decisions throughout their course of treatment and at end of life (EOL). These decisions can be influenced by their family caregivers’ preferences for the patient’s cancer treatment. Methods Using a longitudinal, descriptive study design from an on-going study, data were collected on an adult sample of patients with advanced stage GI or lung cancers and their family caregivers (n=237). Using a one item visual analog scale (0–100 with higher number indicating a preference for length of life over quality of life), patients and family caregivers were asked “regarding your/your loved one’s care, what is most important to you right now? ” Data were collected every 3 months until 15 months or patient’s death. Results At enrollment, the preference scores between patients (48.5) and family caregivers (42.6) were closely aligned. At the last assessment prior to death, these scores diverged with the caregivers favoring goals associated with quality of life over length of life (p=.02). Discussion Patients and family caregivers have differing preferences and these goals of care can change over time. Attention to these differences could be used to guide conversations between patients and family caregivers regarding preferences at EOL.