Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytoskeletal tension actively sustains the migratory T‐cell synaptic contact

When migratory T cells encounter antigen‐presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T‐cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen‐triggered mechanism that actively promotes T‐cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott–Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T‐cell activation, WASP is degraded, leading to cytoskeletal unraveling and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell–APC synaptic contact.
Lysine Methyltransferases Signaling: Histones are Just the Tip of the Iceberg.

Protein lysine methylation is a functionally diverse post-translational modification involved in various major cellular processes. Lysine methylation can modulate proteins activity, stability, localization and/or interaction, resulting in specific downstream signaling and biological outcomes. Lysine methylation is a dynamic and fine-tuned process, deregulation of which often leads to human pathologies. In particular, the lysine methylome and its associated signaling network can be linked to carcinogenesis and cancer progression. Histone modifications and chromatin regulation is a major aspect of lysine methylation importance, but increasing evidence suggests that a high relevance and impact of non-histone lysine methylation signaling has emerged in recent years. In this review, we draw an updated picture of the current scientific knowledge regarding non-histone lysine methylation signaling and its implication in physiological and pathological processes. We aim to demonstrate the significance of lysine methylation as a major and yet underestimated posttranslational modification, and to raise the importance of this modification in both epigenetic and cellular signaling by focusing on the observed activities of SET- and 7β-strand- containing human lysine methyltransferases. Recent evidence suggests that what has been observed so far regarding lysine methylation's implication in human pathologies is only the tip of the iceberg. Therefore, the exploration of the "methylome network" raises the possibility to use these enzymes and their substrates as promising new therapeutic targets for the development of future epigenetic and methyllysine signaling cancer treatments.
Developing preliminary blood metabolomics-based biomarkers of insufficient sleep in humans.

STUDY OBJECTIVE Identify small molecule biomarkers of insufficient sleep using untargeted plasma metabolomics in humans undergoing experimental insufficient sleep. METHODS We conducted a cross-over laboratory study where 16 normal weight participants (8 men; age 22 ± 5 years; body mass index < 25 kg/m2) completed three baseline days (9h sleep opportunity per night) followed by five day insufficient (5h sleep opportunity per night) and adequate (9h sleep opportunity per night) sleep conditions. Energy balanced diets were provided during baseline, with ad libitum energy intake provided during the insufficient and adequate sleep conditions. Untargeted plasma metabolomics analyses were performed using blood samples collected every 4h across the final 24h of each condition. Biomarker models were developed using logistic regression and linear support vector machine algorithms. RESULTS The top performing biomarker model was developed by linear support vector machine modeling, consisted of 65 compounds, and discriminated insufficient versus adequate sleep with 74% overall accuracy and a Matthew's Correlation Coefficient of 0.39. The compounds in the top performing biomarker model were associated with ATP Binding Cassette Transporters in Lipid Homeostasis, Phospholipid Metabolic Process, Plasma Lipoprotein Remodeling, and sphingolipid metabolism. CONCLUSION We identified potential metabolomics-based biomarkers of insufficient sleep in humans. Although our current biomarkers require further development and validation using independent cohorts, they have potential to advance our understanding of the negative consequences of insufficient sleep, improve diagnosis of poor sleep health, and could eventually help identify targets for countermeasures designed to mitigate the negative health consequences of insufficient sleep.
Discrepant Perception of Lupus Disease Activity: A Comparison Between Patients' and Physicians' Disease Activity Scores.

OBJECTIVE The aim of this study was to compare patient and physician (MD) assessment of disease activity in systemic lupus erythematosus patients. METHODS This cross-sectional study was conducted between August 2016 and December 2017 at 2 Peruvian hospitals. One group assessed disease activity using a visual analog scale (VAS, 0-100 mm) and the other one using a numerical rating scale (NRS, 0-4), before and after their MD's visit. MDs assessed it with the Mexican Systemic Lupus Erythematosus Disease Activity (Mex-SLEDAI) (0-32) and with the SLICC/ACR Damage Index (SDI) for damage. Health-related quality of life was ascertained with the LupusQoL. Visual analog scale and NRS were compared using the Wilcoxon signed-rank test and the correlation between disease activity as assessed by the patient and the Mex-SLEDAI, SDI, and LupusQoL with the Spearman rank correlation. RESULTS Two hundred forty patients were included; mean (SD) age at diagnosis was 34.9 (12.9) years; most patients were Mestizo. Disease duration was 10.1 (7.0) years. The Mex-SLEDAI was 1.9 (2.7) and the SDI 1.2 (1.5). Disease activity as assessed by the patient, either by VAS or NRS, did not correlate with the Mex-SLEDAI or the SDI. In contrast, patient assessment of disease activity, by VAS or NRS, significantly correlated with several components of the LupusQoL (physical health, pain, planning, emotional health, and fatigue). CONCLUSIONS Physician's and patient's assessments of disease activity are discrepant; overall, patients score higher than their MDs. Patients score how they perceive the disease is affecting them, rather than disease activity per se. The VAS could be more useful than the NRS as a measurement of disease activity.
Bremelanotide: New Drug Approved for Treating Hypoactive Sexual Desire Disorder

Objective: To review data regarding bremelanotide, a recently approved therapy for hypoactive sexual desire disorder (HSDD). Data Sources: Literature search of Medline, SCOPUS, and EMBASE was performed using the search terms bremelanotide, bremelanotide injection, Vyleesi, and melanocortin 4 receptor agonist between January 1, 1996, and December 15, 2019. Reference lists from included articles were also reviewed for pertinent citations. Study Selection/Data Extraction: We included phase 2 and 3 trials of bremelanotide. There were 2 reports of phase 3 trials and 2 reports of phase 2 trials. Additional information from supplementary analyses was also referenced. Data Synthesis: Bremelanotide demonstrates significant improvement in desire and a significant decrease in distress related to lack of desire. The most common adverse effects include nausea (39.9%), facial flushing (20.4%), and headache (11%). Relevance to Patient Care and Clinical Practice: Bremelanotide is the second Food and Drug Administration–approved medication for the treatment of HSDD. Bremelanotide’s place in therapy is unknown, as the HSDD guidelines were last updated in 2017. Although the trials met statistical significance for change in sexual desire elements and distress related to sexual desire, the clinical benefit may only be modest. Conclusion: Bremelanotide is a subcutaneous injection that can be administered as needed approximately 45 minutes prior to sexual activity. Bremelanotide is safe and has limited drug-drug interactions, including no clinically significant interactions with ethanol. Prescribing guidelines recommend no more than 1 dose in 24 hours and no more than 8 doses per month. Individuals should discontinue use after 8 weeks without benefit.
Burnout among medical and health sciences information professionals who support systematic reviews: an exploratory study

Objective The aim of this exploratory study was to assess personal, work-related, and client-related burnout among information professionals who support systematic review (SR) work. Methods The Copenhagen Burnout Inventory, a validated tool for assessing burnout, was administered to information professionals who support SR work. A broad range of health sciences or medical librarians and information professionals were targeted via professional email discussion lists and news outlets. Questionnaire responses were captured electronically using Qualtrics Survey Software and quantitatively analyzed. Results Respondents experienced an average personal burnout score of 48.6, work-related score of 46.4, and client-related score of 32.5 out of 100. Respondents who reported spending >80% of their job duties on SR work had significantly lower personal burnout scores than those who reported spending <10% of their job duties on SR work (average, 31.5 versus 50.9, respectively). Also, respondents who reported using an SR support tool had significantly lower personal burnout scores than those who reported sometimes using a tool (average, 43.7 versus 54.7, respectively). Conclusion The results suggest that information professionals who dedicate more time to SR work or who consistently use an SR support tool experience less burnout. This study provides groundwork for further investigation with the aim of developing approaches to prevent or combat SR-related burnout among information professionals.
Prenatal ethanol exposure enhances the susceptibility to depressive behavior of adult offspring rats fed a high-fat diet by affecting BDNF-associated pathway

Epidemiological studies have shown that exposure to ethanol during pregnancy can result in an increased risk for depression in offspring. A 'brain-derived neurotrophic factor (BDNF) hypothesis' has been proposed to help explain the pathogenic mechanism of depression. This study was designed to verify the enhanced susceptibility to depression in prenatal ethanol exposure (PEE) offspring rats and explore possible intrauterine programming mechanisms related to the BDNF signaling pathway. Pregnant rats were intragastrically administrated ethanol (4 g/kg/day) from gestational day 11 until term delivery. All offspring rats were given a high-fat diet after weaning. Then the behavior tests, including sucrose preference test and open field test, were performed to adult offspring rats. The histomorphology of hippocampus was examined, and the expression of genes related to the BDNF signaling pathway was detected in the hippocampus of PEE offspring. The PEE female adult offspring rats showed depression-like behavior, with obvious morphological injury in hippocampus. Additionally, the mRNA expression levels of glucocorticoid receptor (GR) and BDNF pathway-associated genes were changed in hippocampus. Multigene RT-qPCR also revealed that the mRNA expression levels for BDNF pathway-associated genes and synaptic plasticity genes were decreased in the hippocampus of fetal offspring rats in the PEE group. The underlying mechanism involves an increased GR expression that constantly suppresses the BDNF signaling pathway, and aggravates the functional insult to the hippo-campus, resulting in an increased susceptibility to depression among PEE female adult offspring rats. Results of the present study provide theoretical and experimental evidence that can be used for the early prevention and treatment of depression.
Altered expression of fucosylation pathway genes is associated with poor prognosis and tumor metastasis in non-small cell lung cancer

Fucosylation is a post-translational modification that attaches fucose residues to protein- or lipid-bound oligosaccharides. Certain fucosylation pathway genes are aberrantly expressed in several types of cancer, including non-small cell lung cancer (NSCLC), and this aberrant expression is associated with poor prognosis in patients with cancer. However, the molecular mechanism by which these fucosylation pathway genes promote tumor progression has not been well-characterized. The present study analyzed public microarray data obtained from NSCLC samples. Multivariate analysis revealed that altered expression of fucosylation pathway genes, including fucosyltransferase 1 (FUT1), FUT2, FUT3, FUT6, FUT8 and GDP-L-fucose synthase (TSTA3), correlated with poor survival in patients with NSCLC. Inhibition of FUTs by 2F-peracetyl-fucose (2F-PAF) suppressed transforming growth factor β (TGFβ)-mediated Smad3 phosphorylation and nuclear translocation in NSCLC cells. In addition, wound-healing and Transwell migration assays demonstrated that 2F-PAF inhibited TGFβ-induced NSCLC cell migration and invasion. Furthermore, in vivo bioluminescence imaging analysis revealed that 2F-PAF attenuated the metastatic capacity of NSCLC cells. These results may help characterize the oncogenic role of fucosylation in NSCLC biology and highlight its potential for developing cancer therapeutics.
Effect of Sport-Specific Constraints on Aerobic Capacity in High School Field Hockey Players

Abstract Roberts, AH, Walden, AJ, Carter, KA, and Symons, TB. Effect of sport-specific constraints on aerobic capacity in high school field hockey players. J Strength Cond Res 36(2): 493–497, 2022—Many sports require the use of a mouth guard (MG) and carrying an object during play. Research has shown that individually these conditions can cause performance decrements; however, no research has been conducted into the effect of combining both mouth guard and stick with adolescent female field hockey players. This study aimed to determine the effects of MG and stick (STK) use on estimated aerobic capacity over the course of a season long training and competition period. Thirty-eight female high school field hockey players were separated into 2 groups: experimental (EXP—all training with MG-STK) or control (CTL—all training without MG-STK). Aerobic capacity was estimated using a multi-stage fitness test. Field hockey specific training prescribed by coaching staff was performed throughout the study, with testing at pre-, mid- and post-season. Subjects performed 2 sets of testing at each time point, first without MG-STK (WOMG-STK) and then with MG-STK. No main effect was observed in aerobic capacity estimations between groups; however, MG-STK testing reduced estimated aerobic capacity at each time point, regardless of the group (WOMG-STK: 37.4 ± 6. mL·kg−1·min−1 vs. MG-STK: 33.2 ± 4. mL·kg−1·min−1; p < 0.01). Chronic use of MG-STK does not seem to negatively impact estimates of aerobic capacity over the course of a season in high school field hockey players. Therefore, players should be encouraged to use MGs during all training sessions as it increases safety and familiarity with no decrement in long-term physiological performance.
Pediatric Firearm Mortality in the United States, 2010-2016: A National Trauma Data Bank Analysis.

BACKGROUND Pediatric firearm injury is a leading cause of death for U.S. children. We sought to further characterize children who die from these injuries using a validated national database. METHODS The National Trauma Data Bank 2010-2016 was queried for patients ages 0 to 19 years old. International Classification of Diseases external cause of injury codes were used to classify patients by intent. Differences between groups were analyzed using chi-squared or Mann-Whitney U tests. Patterns over time were analyzed using non-parametric tests for trend. Multivariable logistic regression was employed to investigate associations between the above factors and mortality. RESULTS There were a total of 45,288 children with firearm injuries, 12.0% (n = 5,412) who died. Those who died were younger and more often white than survivors. Mortality was associated with increased injury severity, shock on presentation, and polytrauma (p < 0.001 for all). There was an increasing trend in the proportion of self-inflicted injuries over the study period (p < 0.001), and mortality from these self-inflicted injuries increased concordantly (35.3% in 2010 to 47.8% in 2016, p = 0.001). Location of severe injuries had significant different mortality rates, ranging from 51.3% of head injuries to 3.9% in the extremities. In the multivariable model, treatment at a pediatric trauma center was protective against mortality, with ORs of 2.10 (CI: 1.64 - 2.68) and 1.80 (CI: 1.39 - 2.32) for death at adult and dual-designated trauma centers, respectively. This finding was confirmed in age-stratified cohorts. CONCLUSIONS Proportions of self-inflicted pediatric firearm injury in the NTDB increased from 2010 to 2016, as did mortality from self-inflicted injury. As mortality is highest in this subpopulation, prevention and treatment efforts should be prioritized in this group of firearm-injured children. LEVEL OF EVIDENCE III - Retrospective cohort study.
Simultaneous identification of the three active constituents in Lung-Ventilating-Regulating Oral Liquid by RP-HPLC.

The study aimed to develop a HPLC method for ephedrine, hesperidin, and baicalin in Lung-Ventilating-Regulating Oral Liquid. The three active constituents were identified in an Agilent TC-C18 (2) chromatographic column (250mm × 4.6mm, 5μm), with 0.2% phosphoric acid solution - methyl cyanides as mobile phase, which was performed at a gradient elution column temperature of 25oC and a flow rate of 0.8 mL•min-1. Then the eluate was detected at detection wavelengths of 207 nm (for ephedrine) and 278 nm (for hesperidin and baicalin). Under the chromatographic conditions, ephedrine, hesperidin, and baicalin were well separated, which showed good linear relationships at 0.158-2.370, 0.164-4.100 and 0.160-4. 000μg, respectively. The coefficients of recovery of these three kinds of samples showed 100.2%, 98.7% and 97.8%, respectively. The developed method is convenient, accurate and well repeatable, and consequently can be applied for the quality control of Lung-Ventilating-Regulating Oral Liquid.
Online interventions aimed at reducing psychological distress in cancer patients: evidence update and suggestions for future directions.

PURPOSE OF REVIEW A great proportion of people affected by cancer experience psychological distress. To reduce pressure on limited health-management resources available, evidence-based eHealth or online interventions can fill an important gap by making psychosocial care more easily accessible. However, evidence of their effectiveness is mixed. This present review provides an update on the effectiveness of online interventions in reducing psychological distress in patients with cancer by including studies published from January 2018 to September 2019. RECENT FINDINGS Thirty-three publications describing online interventions were included in the review, including web-based, blended care, telehealth, mHealth, and other online interventions. There was great heterogeneity across studies. The evidence of online interventions' effectiveness in reducing distress was mixed; there was partial support for reduction in psychological distress and depression, but limited evidence for reducing anxiety. Some important limitations should be taken into account when interpreting the results. SUMMARY Online interventions for people affected by cancer, in general, are well received and seem to be a necessary component of comprehensive cancer care. However, these interventions should be more rigorously tested to provide more conclusive evidence about their effectiveness.
The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

Background: Cyclophosphamide is one of the most important chemotherapeutic drugs. Known as a widely accepted treatment strategy, chemotherapy may damage the immune function of cancer patients; as a result, invasive fungal infections (IFIs) occur. Triazole antifungal agents are the most acceptable drugs for IFI treatment, especially those infections caused by chemotherapy. Objective: We aimed to investigate the effects of different triazole antifungal drugs, including fluconazole, itraconazole, and ketoconazole, on the pharmacokinetics (PK) of cyclophosphamide. In addition, we also characterize the potential drug-drug interactions (DDIs) between cyclophosphamide and various triazole antifungal drugs. Methods: The necessary pharmacokinetic parameters and physicochemical data were obtained from published studies. Physiologically based pharmacokinetic (PBPK) models were developed and validated in virtual subjects using Simcyp software. The validated PBPK models were used to evaluate potential DDIs between cyclophosphamide and different triazole antifungal agents in cancer patients. Triazole antifungal agents were simulated by oral administration, whereas cyclophosphamide was simulated by intravenous administration. Results: Simulated plasma concentration-time curves of fluconazole, itraconazole, ketoconazole, and cyclophosphamide were in good consistency with the observed profiles. Our results suggested that the pharmacokinetic parameters of cyclophosphamide were increased by various extents when coadministered with different triazole antifungals. The area under the plasma concentration-time curve of cyclophosphamide was increased when combined with fluconazole, itraconazole, or ketoconazole. Conclusions and Relevance: Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. Our study provides clues that the toxicity and adverse drug reactions that are associated with cyclophosphamide should be closely monitored when coadministered with ketoconazole.
Going around in circles: deciphering the role of circular RNAs in neurodegenerative disease.

PURPOSE OF REVIEW Circular RNAs are highly expressed in the brain, accumulate with ageing and may play important functional roles. Hence, their role in age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, is under active investigation. This review provides an overview of our current knowledge regarding the roles of circular RNAs in Alzheimer's disease and Parkinson's disease. RECENT FINDINGS More studies have examined Alzheimer's disease than Parkinson's disease. Circular RNA 7 (ciRS-7) has been implicated in both diseases and may play a causative pathological role in at least Alzheimer's disease. The identification of circular RNA interaction networks is a primary focus. However, different analysis pipelines can generate quite disparate results, hence bioinformatically identified candidate circular RNAs require experimental and functional validation. SUMMARY Although this field of research is in its infancy, rapid advances holds promise for identifying circular RNAs that are important in neurodegenerative diseases. CiRS-7 is a promising candidate for further examination. More studies are required focussing not only on Alzheimer's disease and Parkinson's disease but also on other neurodegenerative diseases. Whether circular RNAs can be used to inform diagnostic, prognostic and therapeutic strategies for age-related neurodegenerative disease remains unclear.