Miracle-dz/UniFAR-FTUs huggingface dataset:
Determining the Intracortical Responses After a Single Session of Aerobic Exercise in Young Healthy Individuals: A Systematic Review and Best Evidence Synthesis.

Alibazi, RJ, Pearce, AJ, Rostami, M, Frazer, AK, Brownstein, C, and Kidgell, DJ. Determining the intracortical responses after a single session of aerobic exercise in young healthy individuals: a systematic review and best evidence synthesis. J Strength Cond Res XX(X): 000-000, 2020-A single bout of aerobic exercise (AE) may induce changes in the excitability of the intracortical circuits of the primary motor cortex (M1). Similar to noninvasive brain stimulation techniques, such as transcranial direct current stimulation, AE could be used as a priming technique to facilitate motor learning. This review examined the effect of AE on modulating intracortical excitability and inhibition in human subjects. A systematic review, according to PRISMA guidelines, identified studies by database searching, hand searching, and citation tracking between inception and the last week of February 2020. Methodological quality of included studies was determined using the Downs and Black quality index and Cochrane Collaboration of risk of bias tool. Data were synthesized and analyzed using best-evidence synthesis. There was strong evidence for AE not to change corticospinal excitability and conflicting evidence for increasing intracortical facilitation and reducing silent period and long-interval cortical inhibition. Aerobic exercise did reduce short-interval cortical inhibition, which suggests AE modulates the excitability of the short-latency inhibitory circuits within the M1; however, given the small number of included studies, it remains unclear how AE affects all circuits. In light of the above, AE may have important implications during periods of rehabilitation, whereby priming AE could be used to facilitate motor learning.
Provider–patient communication and hospital ratings: perceived gaps and forward thinking about the effects of COVID-19

Abstract Objectives To highlight clinical and operational issues, identify factors that shape patient responses in Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and test the correlations between composite measures and overall hospital ratings. Design Responses to HCAHPS surveys were used in a partial correlation analysis to ascertain those HCAHPS composite measures that most relate to overall hospital ratings. The linear mean scores for the composite measures and individual and global items were analyzed with descriptive analysis and correlation analysis via JMP and SPSS statistical software. Setting HCAHPS is a patient satisfaction survey required by the Centers for Medicare and Medicaid Services for hospitals in the USA. The survey is for adult inpatients, excluding psychiatric patients. Participants 3382 US hospitals. Intervention None. Main Outcome Measure Pearson correlation coefficients for the six composite measures and overall hospital rating. Results The partial correlations for overall hospital rating and three composite measures are positive and moderately strong for care transition (0.445) and nurse communication (0.369) and weak for doctor communication (0.066). Conclusions From a health policy standpoint, it is imperative that hospital administrators stress open and clear communication between providers and patients to avoid problems ranging from misdiagnosis to incorrect treatment. Additional research is needed to determine how the coronavirus of 2019 pandemic influences patients’ perceptions of quality and willingness to recommend hospitals at a time when nurses and physicians show symptoms of burnout due to heavy workloads and inadequate personal protective equipment.
Is borderline personality disorder really an emotion dysregulation disorder and, if so, how? A comprehensive experimental paradigm

Abstract Background Leading theories suggest that borderline personality disorder (BPD) is an emotion dysregulation disorder involving lower basal vagal tone, higher baseline emotion, heightened emotional reactivity, delayed emotional recovery, and emotion regulation deficits. However, the literature to date lacks a unifying paradigm that tests all of the main emotion dysregulation components and comprehensively examines whether BPD is an emotion dysregulation disorder and, if so, in what ways. This study addresses the empirical gaps with a unified paradigm that assessed whether BPD is characterized by five leading emotion dysregulation components compared to generalized anxiety disorder (GAD) and healthy control (HC) groups. Methods Emotion was assessed across self-report, sympathetic, and parasympathetic indices. Participants with BPD, GAD, and HCs (N = 120) first underwent baseline periods assessing basal vagal tone and baseline emotional intensity, followed by rejection-themed stressors assessing emotional reactivity. Participants then either reacted normally to assess emotional recovery or attempted to decrease emotion using mindfulness or distraction to assess emotion regulation implementation deficits. Results Individuals with BPD and GAD exhibited higher self-reported and sympathetic baseline emotion compared to HCs. The BPD group also exhibited self-reported emotion regulation deficits using distraction only compared to the GAD group. Conclusions There is minimal support for several emotion dysregulation components in BPD, and some components that are present appear to be pervasive across high emotion dysregulation groups rather than specific to BPD. However, BPD may be characterized by problems disengaging from emotion using distraction.
KCa3.1-dependent uptake of the cytotoxic DNA-binding dye Hoechst 33258 into cancerous but not healthy cervical cells

The poor and nonselective penetration of current chemotherapeutics across the plasma membranes of cancer cells, which is necessary for the targeted disruption of the intracellular machinery, remains a major pharmaceutical challenge. In several cell types, including mast cells and macrophages, exposure to extracellular ATP is known to stimulate passive entry of large and otherwise membrane impermeable cationic dyes, which is usually attributed to conduction through ionotropic P2X receptors. Here, we report that elevations in cytosolic Ca2+ stimulate the rapid uptake and nuclear accumulation of a DNA-binding fluorescent cation, Hoechst 33258 (H33258), in cervical cancer cells. The H33258 uptake was dependent on activation of intermediate conductance Ca2+-activated K+ channels (KCa3.1), and direct stimulation of the channel with the activators SKA 31 and DCEBIO was sufficient to induce cellular uptake of H33258 directly. In contrast to the results from cancerous cervical cells, KCa3.1-dependent H33258 uptake was rarely observed in epithelial cells derived from the ectocervix and transformation zone of healthy cervical tissue. Furthermore, whole-cell patch clamp experiments and assessment of membrane potential using the slow voltage-sensitive dye bis-(1,3-diethylthiobarbituric acid)trimethine oxonol revealed a significant difference in functional KCa3.1 activity between cancerous and healthy cervical epithelial cells, which correlated strongly with the incidence of KCa3.1-dependent H33258 uptake. Finally, we show that activation of KCa3.1 channels caused a modest but significant sensitization of cancer cells to the growth suppressant effects of H33258, lending plausibility to the idea of using KCa3.1 channel activators to enhance cell penetration of small cationic toxins into cancer cells expressing these channels.
GPR173 agonist phoenixin 20 promotes osteoblastic differentiation of MC3T3-E1 cells

Osteogenic differentiation is critical to bone homeostasis, and its imbalance plays a key role in the progression of osteoporosis. Osteoblast cells are responsible for synthesizing new bone tissue, and understanding how to control osteoblastic differentiation is vital to the treatment of osteoporosis. Herein, we show that GPR173 signaling is involved in the regulation of osteoblastic differentiation in MC3T3-E1 cells. Our data reveals that GPR173 is abundantly expressed in MC3T3-E1 cells, and its expression is inducible upon the introduction of osteogenic media. The activation of GPR173 by its selective agonist phoenixin 20 induces the expression of several osteoblast signature genes including collagen type 1 alpha 1 (Col-I), osteocalcin (OCN), alkaline phosphatase (ALP) as well as increased matrix mineralization and ALP activity, suggesting that the activation of GPR173 promotes osteoblastic differentiation. Moreover, we show that the effect of phoenixin 20 is mediated by its induction on the key regulator runt-Related Transcription Factor 2 (Runx2). Mechanistically, we display that the action of phoenixin 20 requires the activation of MAPK kinase p38, and deactivation of p38 by its inhibitor SB203580 weakens the phoenixin 20-mediated induction of RUNX-2, ALP, and matrix mineralization. Silencing of GPR173 attenuates phoenixin 20-mediated osteoblastic differentiation, indicating its dependence on the receptor. Collectively, our study reveals a new role of GPR173 and its agonist phoenixin 20 in osteoblastic differentiation.
Preoperative atrial fibrillation in association with reduced haemoglobin predicts increased 30-d mortality after cardiac surgery

Abstract Objectives Atrial fibrillation is the most common arrhythmia occurring after cardiac surgery. Less attention has been focused on preoperative atrial fibrillation and anaemia as risk factors for mortality after cardiac surgery. The aim of this study was to determine preoperative risk factors for 30-d mortality after open-heart surgery. Design. The study population consisted of 2015 patients (73.4% men; mean age 68 years) undergoing coronary artery bypass grafting (CABG) (52.0%), aortic valve replacement (AVR) (18.6%), AVR and CABG (10.0%), mitral valve plasty or replacement (14.0%), and AVR and aortic root reconstruction (ARR) (5.5%) in Kuopio University Hospital from January 2013 to December 2016. Univariate and multivariate Cox proportional hazards models were used for statistical analyses. Kaplan–Meier survival curves were generated. Results. Total 30-d mortality was 1.8%. By Cox regression analysis, predictors of 30-d mortality (hazard ratio [HR] [95% confidence interval [CI]]) included female gender (1.95 [1.00–3.77]), preoperative atrial fibrillation, (2.38 [1.12–5.03]) reduced haemoglobin level (3.40 [1.47–7.90]), and pulmonary congestion (3.16 [1.52–6.55]). The combination of preoperative reduced haemoglobin and preoperative atrial fibrillation was a strong predictor (12.37 [4.40–34.77], p < .001). Estimated glomerular filtration rate (eGFR) predicted 30-d mortality in univariate models but was not an independent predictor in multivariate models. Conclusions. According to the main findings of our study, the combination of preoperative atrial fibrillation and reduced haemoglobin level substantially increase the risk of 30-d mortality after cardiac surgery. Identification of high-risk patients pre-operatively could help to make optimal clinical decisions for timing of operation and perioperative treatment.
Epigenome engineering: new technologies for precision medicine

Abstract Chromatin adopts different configurations that are regulated by reversible covalent modifications, referred to as epigenetic marks. Epigenetic inhibitors have been approved for clinical use to restore epigenetic aberrations that result in silencing of tumor-suppressor genes, oncogene addictions, and enhancement of immune responses. However, these drugs suffer from major limitations, such as a lack of locus selectivity and potential toxicities. Technological advances have opened a new era of precision molecular medicine to reprogram cellular physiology. The locus-specificity of CRISPR/dCas9/12a to manipulate the epigenome is rapidly becoming a highly promising strategy for personalized medicine. This review focuses on new state-of-the-art epigenome editing approaches to modify the epigenome of neoplasms and other disease models towards a more ‘normal-like state’, having characteristics of normal tissue counterparts. We highlight biomolecular engineering methodologies to assemble, regulate, and deliver multiple epigenetic effectors that maximize the longevity of the therapeutic effect, and we discuss limitations of the platforms such as targeting efficiency and intracellular delivery for future clinical applications.
Investigation of intestinal transportation of peptide‐displaying bacteriophage particles using phage display method

To investigate whether peptide sequences with specific translocation across the gastrointestinal barrier can be identified as drug delivery vehicles, in vivo phage display was conducted. For this purpose, a random library of 12‐mer peptides displayed on M13 bacteriophage was orally administered to mice followed by recovery of the phage particles from the blood samples after three consecutive biopanning rounds. The obtained peptide sequences were analyzed using bioinformatics tools and software. The results demonstrated that M13 bacteriophage bearing peptides translocate nonspecifically across the mice intestinal mucosal barrier deduced from random distribution of amino acids in different positions of the identified peptide sequences. The most probable reason for entering the phage particles into systemic circulation after oral administration of the peptide library can be related to the nanoscale nature of their structures which provides a satisfying platform for the purpose of designing nanocarriers in pharmaceutical applications.
Alterations in BDNF Protein Concentrations in the Hippocampus do not Explain the Pro-Neurogenic Effect of Citalopram on Adult Neurogenesis

Abstract Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in the pro-neurogenic effect of selective serotonin reuptake inhibitors. In this study, we used Tph2 −/− mice lacking brain serotonin to dissect the interplay between BDNF and the serotonin system in mediating the effects of antidepressant pharmacotherapy on adult neurogenesis in the hippocampus. Methods Besides citalopram (CIT), we tested tianeptine (TIA), an antidepressant whose mechanism of action is not well understood. Specifically, we examined cell survival and endogenous concentrations of BDNF following daily injection of the drugs. Results Twenty-one days of CIT, but not of TIA, led to a significant increase in the survival of newly generated cells in the dentate gyrus of wild-type mice, without a significant effect on BDNF protein levels by either treatment. In Tph2 −/− mice, adult neurogenesis was consistently increased. Furthermore, Tph2 −/− mice showed increased BDNF protein levels, which were not affected by TIA but were significantly reduced by CIT. Discussion We conclude that the effects of CIT on adult neurogenesis are not explained by changes in BDNF protein concentrations in the hippocampus.
Cinnamides Target Leishmania amazonensis Arginase Selectively

Caffeic acid and related natural compounds were previously described as Leishmania amazonensis arginase (L-ARG) inhibitors, and against the whole parasite in vitro. In this study, we tested cinnamides that were previously synthesized to target human arginase. The compound caffeic acid phenethyl amide (CAPA), a weak inhibitor of human arginase (IC50 = 60.3 ± 7.8 μM) was found to have 9-fold more potency against L-ARG (IC50 = 6.9 ± 0.7 μM). The other compounds that did not inhibit human arginase were characterized as L-ARG, showing an IC50 between 1.3–17.8 μM, and where the most active was compound 15 (IC50 = 1.3 ± 0.1 μM). All compounds were also tested against L. amazonensis promastigotes, and only the compound CAPA showed an inhibitory activity (IC50 = 80 μM). In addition, in an attempt to gain an insight into the mechanism of competitive L-ARG inhibitors, and their selectivity over mammalian enzymes, we performed an extensive computational investigation, to provide the basis for the selective inhibition of L-ARG for this series of compounds. In conclusion, our results indicated that the compounds based on cinnamoyl or 3,4-hydroxy cinnamoyl moiety could be a promising starting point for the design of potential antileishmanial drugs based on selective L-ARG inhibitors.
Comprehensive Phenotyping of Human Dendritic Cells and Monocytes

Professional antigen‐presenting cells (APCs), which include dendritic cells (DCs) and monocytes are essential for inducing and steering adaptive T‐cell responses. Recent technological developments in single‐cell analysis have significantly advanced our understanding of APC subset heterogeneity. To accurately resolve this functional diversity and to account for tissue‐specific adaptation, novel phenotyping markers have been described more recently. While some of these largely overlap with traditionally used markers, more fine‐grained phenotyping might be essential during inflammatory settings, where the traditional distinction between monocytes and dendritic cells has become blurred. Within this phenotype report, we provide a concise overview of traditional and recently described markers for the phenotyping of DCs and monocytes in the human system.
Scaling-Up Performance-Based Financing in Burkina Faso: From PBF to User Fees Exemption Strategic Purchasing

Background: Numerous countries have undertaken performance-based financing (PBF) reforms to improve quality and quantity of healthcare services. However, only few reforms have successfully managed to achieve the different scale-up phases. In Burkina Faso, a pilot project was implemented, but was put on hold before being scaled. During the writing of this article, discussions to scale-up were still ongoing on a national strategic purchasing strategy within a government led user fee exemption policy. Methods: This study’s objective is to identify facilitators and barriers to scaling-up for that pilot, based on the World Health Organization’s (WHO’s) theoretical framework. Interviews were conducted in three health centres and in Ouagadougou to discuss the scale-up with different actors. The software QDA Miner© was used to help in the framework analysis. Results: The low involvement of some key stakeholders (mainly decision-makers) and the unstable context hindered ownership of the project, thus its priority on the political agenda. PBF reform therefore lost its momentum to the benefit of a user fee exemption policy. This latter program was seen to be more beneficial since it addressed access to healthcare services, in comparison to service quality, which was the PBF’s relative advantage. A scale-up of some PBF elements (eg, strategic purchasing tools) is however still in discussion in 2019, but would be integrated within the user fee exemption program. Increased costs during the PBF’s implementation gave the impression that the project was too costly and not scalable. The involvement of an important funding agency (World Bank, WB) also fed the impression of high costs, which demotivated the actors, especially decision-makers. Conclusion: Contextual factors remain central to the implementation of PBF, while their evaluation and mitigation have remained unclear. The participation of key actors in scaling-up operations and the use of social science as tools to better understand the context is therefore primordial.
Brain Metastasis from Unknown Primary Tumour: Moving from Old Retrospective Studies to Clinical Trials on Targeted Agents

Simple Summary Brain metastases (BMs) are the most common intracranial tumours in adults and occur up to 3–10 times more frequently than primary brain tumours. In up to 15% of patients with BM, the primary tumour cannot be identified. These cases are known as BM of cancer of unknown primary (CUP) (BM-CUP). The understanding of BM-CUP, despite its relative frequency and unfavourable outcome, is still incomplete and clear indications on management are missing. The aim of this review is to summarize current evidence on the diagnosis and treatment of BM-CUP. Abstract Brain metastases (BMs) are the most common intracranial tumours in adults and occur up to 3–10 times more frequently than primary brain tumours. BMs may be the cause of the neurological presenting symptoms in patients with otherwise previously undiagnosed cancer. In up to 15% of patients with BMs, the primary tumour cannot be identified. These cases are known as BM of cancer of unknown primary (CUP) (BM-CUP). CUP has an early and aggressive metastatic spread, poor response to chemotherapy, and poor prognosis. The pathogenesis of CUP seems to be characterized by a specific underlying pro-metastatic signature. The understanding of BM-CUP, despite its relative frequency and unfavourable outcome, is still incomplete and clear indications on management are missing. Advances in diagnostic tools, molecular characterization, and target therapy have shifted the paradigm in the approach to metastasis from CUP: while earlier studies stressed the importance of finding the primary tumour and deciding on treatment based on the primary diagnosis, most recent studies focus on the importance of identifying targetable molecular markers in the metastasis itself. The aim of this review is to summarize current evidence on BM-CUP, from the diagnosis and pathogenesis to the treatment, with a focus on available studies and ongoing clinical trials.
Molecular mechanisms of plant adaptive responses to heavy metals stress

Heavy metals (HMs) are among the main environmental pollutants that can enter the soil, water bodies, and the atmosphere as a result of natural processes (weathering of rocks, volcanic activity), and also as a result of human activities (mining, metallurgical and chemical industries, transport, application of mineral fertilizers). Plants counteract the HMs stresses through morphological and physiological adaptations, which are imparted through well‐coordinated molecular mechanisms. New approaches, which include transcriptomics, genomics, proteomics, and metabolomics analyses, have opened the paths to understand such complex networks. This review sheds light on molecular mechanisms included in plant adaptive and defense responses during metal stress. It is focused on the entry of HMs into plants, its transport and accumulation, effects on the main physiological processes, gene expressions included in plant adaptive and defense responses during HM stress. Analysis of new data allowed the authors to conclude that the most important mechanism of HM tolerance is extracellular and intracellular HM sequestration. Organic anions (malate, oxalate, etc.) provide extracellular sequestration of HM ions. Intracellular HM sequestration depends not only on a direct binding mechanism with different polymers (pectin, lignin, cellulose, hemicellulose, etc.) or organic anions but also on the action of cellular receptors and transmembrane transporters. We focused on the functioning chloroplasts, mitochondria, and the Golgi complex under HM stress. The currently known molecular mechanisms of plant tolerance to the toxic effects of HMs are analyzed.