Miracle-dz/UniFAR-FTUs huggingface dataset:
Interference of Hsp27 Results in Apoptosis Induced by Photodamage via Regulation of Subcellular Localization of p21 in Immortalized Human Keratinocytes

Background Owing to the increased incidence of photodermatosis caused by ultraviolet light in recent years, it is necessary to clarify the mechanisms potential photodamage to the skin and reveal possible therapeutic targets. Heat shock protein 27 (Hsp27) is well known for suppressing apoptosis. The aim of present study was to elucidate possible photoprotective mechanism between Hsp27 and p21 on ultraviolet B (UVB)-induced photodamage. Material/Methods The Hsp27 gene was interfered to assess the expression of its downstream effectors, cell apoptosis, and cell proliferation ability. The cell apoptosis was tested using flow cytometry method. The cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8) assay. The expression of protein was tested using western-blotting method. The expression of mRNA was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The subcellular localization was elucidated using immunofluorescence. Results Hsp27 knockdown decreased cell viability and increased the incidence of UVB-induced apoptosis. Compared with control group, activation of phosphorylated-Akt (p-Akt)-dependent pathway resulted in the nuclear accumulation of p21 and suppression of cell proliferation, while promoting apoptosis in Hsp27 knockdown group. In addition, Hsp27 knockdown increased p53 expression and the Bax: Bcl-2 ratio, which further accelerated the apoptotic process. Conclusions These findings complemented the mechanism of skin photodamage and demonstrated the photoprotective mechanisms of Hsp27 in HaCaT cells, which might implicate a potential therapeutic target of photodamage and photodermatosis.
An Examination of John Henryism, Trust, and Medication Adherence Among African Americans With Hypertension

Background. John Henryism is defined as a measure of active coping in response to stressful experiences. John Henryism has been linked with health conditions such as diabetes, prostate cancer, and hypertension, but rarely with health behaviors. Aims. We hypothesized that reporting higher scores on the John Henryism Scale may be associated with poorer medication adherence, and trust in providers may mediate this relationship. Method. We tested this hypothesis using data from the TRUST study. The TRUST study included 787 African Americans with hypertension receiving care at a safety-net hospital. Ordinal logistic regression was used to examine the relationship between John Henryism and medication adherence. Results. Within our sample of African Americans with hypertension, lower John Henryism scores was associated with poorer self-reported adherence (low, 20.62; moderate, 19.19; high, 18.12; p < .001). Higher John Henryism scores were associated with lower trust scores (low John Henryism: 40.1; high John Henryism: 37.9; p < .001). In the adjusted model, each 1-point increase in the John Henryism score decreased the odds of being in a better cumulative medication adherence category by a factor of 4% (odds ratio = 0.96, p = .014, 95% confidence interval = 0.93-0.99). Twenty percent of the association between medication adherence and John Henryism was mediated by trust (standard deviation = 0.205, 95% confidence interval = 0.074-0.335). Discussion. This study provides important insights into the complex relationship between psychological responses and health behaviors. It also contributes to the body of literature examining the construct of John Henryism among African Americans with hypertension. Conclusion. The findings of this study support the need for interventions that promote healthful coping strategies and patient–provider trust.
A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia

We conducted a prospective, multicenter study to evaluate the efficacy and safety of low‐dose decitabine in adult patients with refractory immune thrombocytopenia. Adult patients who did not respond to, did not tolerate, or were unwilling to undergo splenectomy, with either a baseline platelet count less than 30 × 109/L or the presence of bleeding symptoms and further need of ITP‐specific treatments, were enrolled. Patients received decitabine at 3.5 mg/m2 intravenously for three consecutive days per cycle, for three cycles with a four‐week interval between cycles. All patients were assessed every week during the first 12 weeks and at four‐week intervals thereafter. We screened 49 patients for eligibility. Four patients were excluded and 45 received decitabine. At the end of decitabine treatment, complete response was achieved in eight patients (17.78%), and partial response was achieved in 15 patients (33.33%). The median time to initial response was 28 days (range, 14‐70 days). Furthermore, seven relapsed patients received decitabine retreatment and all showed platelet response, including one complete response and six partial responses. Sustained response rates at 6, 12 and 18 months were 44.44% (20/45), 31.11% (14/45) and 20.0% (9/45), respectively. For responders, immune thrombocytopenia‐related symptoms, fatigue, psychological health, fear, and overall quality of life were significantly improved. Adverse events were observed in 13 (28.89%) patients. No serious adverse events were recorded. In conclusion, low dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia. This trial is registered with clinicaltrials.gov identifier: NCT01568333.
Photobiomodulation Mitigates Cerebrovascular Leakage Induced by the Parkinsonian Neurotoxin MPTP

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to model Parkinson’s disease (PD) as it specifically damages the nigrostriatal dopaminergic pathway. Recent studies in mice have, however, provided evidence that MPTP also compromises the integrity of the brain’s vasculature. Photobiomodulation (PBM), the irradiation of tissue with low-intensity red light, mitigates MPTP-induced loss of dopaminergic neurons in the midbrain, but whether PBM also mitigates MPTP-induced damage to the cerebrovasculature has not been investigated. This study aimed to characterize the time course of cerebrovascular disruption following MPTP exposure and to determine whether PBM can mitigate this disruption. Young adult male C57BL/6 mice were injected with 80 mg/kg MPTP or isotonic saline and perfused with fluorescein isothiocyanate FITC-labelled albumin at various time points post-injection. By 7 days post-injection, there was substantial and significant leakage of FITC-labelled albumin into both the substantia nigra pars compacta (SNc; p < 0.0001) and the caudate-putamen complex (CPu; p ≤ 0.0003); this leakage partly subsided by 14 days post-injection. Mice that were injected with MPTP and treated with daily transcranial PBM (670 nm, 50 mW/cm2, 3 min/day), commencing 24 h after MPTP injection, showed significantly less leakage of FITC-labelled albumin in both the SNc (p < 0.0001) and CPu (p = 0.0003) than sham-treated MPTP mice, with levels of leakage that were not significantly different from saline-injected controls. In summary, this study confirms that MPTP damages the brain’s vasculature, delineates the time course of leakage induced by MPTP out to 14 days post-injection, and provides the first direct evidence that PBM can mitigate this leakage. These findings provide new understanding of the use of the MPTP mouse model as an experimental tool and highlight the potential of PBM as a therapeutic tool for reducing vascular dysfunction in neurological conditions.
Small angle X‐ray scattering‐assisted protein structure prediction in CASP13 and emergence of solution structure differences

Small angle X‐ray scattering (SAXS) measures comprehensive distance information on a protein's structure, which can constrain and guide computational structure prediction algorithms. Here, we evaluate structure predictions of 11 monomeric and oligomeric proteins for which SAXS data were collected and provided to predictors in the 13th round of the Critical Assessment of protein Structure Prediction (CASP13). The category for SAXS‐assisted predictions made gains in certain areas for CASP13 compared to CASP12. Improvements included higher quality data with size exclusion chromatography‐SAXS (SEC‐SAXS) and better selection of targets and communication of results by CASP organizers. In several cases, we can track improvements in model accuracy with use of SAXS data. For hard multimeric targets where regular folding algorithms were unsuccessful, SAXS data helped predictors to build models better resembling the global shape of the target. For most models, however, no significant improvement in model accuracy at the domain level was registered from use of SAXS data, when rigorously comparing SAXS‐assisted models to the best regular server predictions. To promote future progress in this category, we identify successes, challenges, and opportunities for improved strategies in prediction, assessment, and communication of SAXS data to predictors. An important observation is that, for many targets, SAXS data were inconsistent with crystal structures, suggesting that these proteins adopt different conformation(s) in solution. This CASP13 result, if representative of PDB structures and future CASP targets, may have substantive implications for the structure training databases used for machine learning, CASP, and use of prediction models for biology.
A look at actions: direct gaze modulates functional connectivity of the right TPJ with an action control network

ABSTRACT Social signals such as eye contact and motor actions are essential elements of social interactions. However, our knowledge about the interplay of gaze signals and the control of actions remains limited. In a group of 30 healthy participants, we investigated the effect of gaze (direct gaze vs averted) on behavioral and neural measures of action control as assessed by a spatial congruency task (spatially congruent vs incongruent button presses in response to gaze shifts). Behavioral results demonstrate that inter-individual differences in condition-specific incongruency costs were associated with autistic traits. While there was no interaction effect of gaze and action control on brain activation, in a context of incongruent responses to direct gaze shifts, a psychophysiological interaction analysis showed increased functional coupling between the right temporoparietal junction, a key region in gaze processing, and the inferior frontal gyri, which have been related to both social cognition and motor inhibition. Conversely, incongruency costs to averted gaze were reflected in increased connectivity with action control areas implicated in top-down attentional processes. Our findings indicate that direct gaze perception inter-individually modulates motor actions and enforces the functional integration of gaze-related social cognition and action control processes, thereby connecting functional elements of social interactions.
Nonsuicidal Self-Injury: Management on the Inpatient Psychiatric Unit

BACKGROUND. Between 4% to 70% of inpatients engage in self-harming behaviors and effective interventions are needed to address this population. AIM. This article reviews literature from 2007 to 2017 to address treatment and management strategies specific for the treatment of nonsuicidal self-injury in the inpatient psychiatric setting. METHODS. Cochrane, PsycINFO, PubMed, and CINAHL were searched for relevant articles with 34 studies reviewed for applicability to the question, and 9 parsed into a summary of Findings table. RESULTS. Therapeutic approaches that show promise include cognitive behavioral therapy, dialectical behavior therapy, and mentalization as well as medications that act on the serotonergic, dopaminergic, and opioid systems. Effective models of care aim toward enhancing therapeutic relationships with staff, providers, and most important, encouraging the internal shift toward recovery within the patient. CONCLUSIONS. More research with controlled designs in the inpatient setting is needed, however, regardless of which approach is used, the impact of the individual caregiver on the patient’s recovery is key.
The Metabolic Concept of Meal Sequence vs. Satiety: Glycemic and Oxidative Responses with Reference to Inflammation Risk, Protective Principles and Mediterranean Diet

With increasing exposure to eating opportunities and postprandial conditions becoming dominant states, acute effects of meals are garnering interest. In this narrative review, meal components, combinations and course sequence were questioned vis-à-vis resultant postprandial responses, including satiety, glycemic, oxidative and inflammatory risks/outcomes vs. protective principles, with reference to the Mediterranean diet. Representative scientific literature was reviewed and explained, and corresponding recommendations discussed and illustrated. Starting meals with foods, courses and/or preloads high in innate/added/incorporated water and/or fibre, followed by protein-based courses, delaying carbohydrates and fatty foods and minimizing highly-processed/sweetened hedonic foods, would increase satiety-per-calorie vs. obesogenic passive overconsumption. Similarly, starting with high-water/fibre dishes, followed by high-protein foods, oils/fats, and delayed/reduced slowly-digested whole/complex carbohydrate sources, optionally closing with simpler carbohydrates/sugars, would reduce glycaemic response. Likewise, starting with foods high in innate/added/incorporated water/fibre/antioxidants, high monounsaturated fatty acid foods/oils, light proteins and whole/complex carbohydrate foods, with foods/oils low in n-6 polyunsaturated fatty acids (PUFA) and n-6:n-3 PUFA ratios, and minimal-to-no red meat and highly/ultra-processed foods/lipids, would reduce oxidative/inflammatory response. Pyramids illustrating representative meal sequences, from most-to-least protective foods, visually communicate similarities between axes, suggesting potential unification for optimal meal sequence, consistent with anti-inflammatory nutrition and Mediterranean diet/meal principles, warranting application and outcome evaluation.
More Impaired Dynamic Ventilatory Muscle Oxygenation in Congestive Heart Failure than in Chronic Obstructive Pulmonary Disease

Patients with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) often have dyspnea. Despite differences in primary organ derangement and similarities in secondary skeletal muscle changes, both patient groups have prominent functional impairment. With similar daily exercise performance in patients with CHF and COPD, we hypothesized that patients with CHF would have worse ventilatory muscle oxygenation than patients with COPD. This study aimed to compare differences in tissue oxygenation and blood capacity between ventilatory muscles and leg muscles and between the two patient groups. Demographic data, lung function, and maximal cardiopulmonary exercise tests were performed in 134 subjects without acute illnesses. Muscle oxygenation and blood capacity were measured using frequency-domain near-infrared spectroscopy (fd-NIRS). We enrolled normal subjects and patients with COPD and CHF. The two patient groups were matched by oxygen-cost diagram scores, New York Heart Association functional classification scores, and modified Medical Research Council scores. COPD was defined as forced expired volume in one second and forced expired vital capacity ratio ≤0.7. CHF was defined as stable heart failure with an ejection fraction ≤49%. The healthy subjects were defined as those with no obvious history of chronic disease. Age, body mass index, cigarette consumption, lung function, and exercise capacity were different across the three groups. Muscle oxygenation and blood capacity were adjusted accordingly. Leg muscles had higher deoxygenation (HHb) and oxygenation (HbO2) and lower oxygen saturation (SmO2) than ventilatory muscles in all participants. The SmO2 of leg muscles was lower than that of ventilatory muscles because SmO2 was calculated as HbO2/(HHb+HbO2), and the HHb of leg muscles was relatively higher than the HbO2 of leg muscles. The healthy subjects had higher SmO2, the patients with COPD had higher HHb, and the patients with CHF had lower HbO2 in both muscle groups throughout the tests. The patients with CHF had lower SmO2 of ventilatory muscles than the patients with COPD at peak exercise (p < 0.01). We conclud that fd-NIRS can be used to discriminate tissue oxygenation of different musculatures and disease entities. More studies on interventions on ventilatory muscle oxygenation in patients with CHF and COPD are warranted.
Protonation state of the selectivity filter of bacterial voltage‐gated sodium channels is modulated by ions

The selectivity filter (SF) of bacterial voltage‐gated sodium channels consists of four glutamate residues arranged in a C4 symmetry. The protonation state population of this tetrad is unclear. To address this question, we simulate the pore domain of bacterial voltage‐gated sodium channel of Magnetococcus sp. (NavMs) through constant pH methodology in explicit solvent and free energy perturbation calculations. We find that at physiological pH the fully deprotonated as well as singly and doubly protonated states of the SF appear feasible, and that the calculated pKa decreases with each additional bound ion, suggesting that a decrease in the number of ions in the pore can lead to protonation of the SF. Previous molecular dynamics simulations have suggested that protonation can lead to a decrease in the conductance, but no pKa calculations were performed. We confirm a decreased ionic population of the pore with protonation, and also observe structural symmetry breaking triggered by protonation; the SF of the deprotonated channel is closest to the C4 symmetry observed in crystal structures of the open state, while the SF of protonated states display greater levels of asymmetry which could lead to transition to the inactivated state which possesses a C2 symmetry in the crystal structure. We speculate that the decrease in the number of ions near the mouth of the channel, due to either random fluctuations or ion depletion due to conduction, could be a self‐regulatory mechanism resulting in a nonconducting state that functionally resembles inactivated states.
Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1‐deficient mice

Polycystic kidney disease (PKD) is characterized by the expansion of fluid‐filled cysts in the kidney, which impair the function of kidney and eventually leads to end‐stage renal failure. It has been previously demonstrated that transgenic overexpression of prothymosin α (ProT) induces the development of PKD; however, the underlying mechanisms remain unclear. In this study, we used a mouse PKD model that sustains kidney‐specific low‐expression of Pkd1 to illustrate that aberrant up‐regulation of ProT occurs in cyst‐lining epithelial cells, and we further developed an in vitro cystogenesis model to demonstrate that the suppression of ProT is sufficient to reduce cyst formation. Next, we found that the expression of ProT was accompanied with prominent augmentation of protein acetylation in PKD, which results in the activation of downstream signal transducer and activator of transcription (STAT) 3. The pathologic role of STAT3 in PKD has been previously reported. We determined that this molecular mechanism of protein acetylation is involved with the interaction between ProT and STAT3; consequently, it causes the deprivation of histone deacetylase 3 from the indicated protein. Conclusively, these results elucidate the significant role of ProT, including protein acetylation and STAT3 activation in PKD, which represent potential for ameliorating the disease progression of PKD. —Chen, Y. ‐C. , Su, Y. ‐C. , Shieh, G. ‐S. , Su, B. ‐H. , Su, W. ‐C. , Huang, P.‐H. , Jiang, S. ‐T. , Shiau, A. ‐L. , Wu, C. ‐L. Prothymosin α promotes STAT3 acetylation to induce cystogenesis in Pkd1‐deficient mice. FASEB J. 33, 13051–13061 (2019). www.fasebj. org
Therapeutic Apheresis in Acute Relapsing Multiple Sclerosis: Current Evidence and Unmet Needs—A Systematic Review

Multiple sclerosis (MS) is the most abundant inflammatory demyelinating disorder of the central nervous system. Despite recent advances in its long-term immunomodulatory treatment, MS patients still suffer from relapses, significantly contributing to disability accrual. In recent years, apheresis procedures such as therapeutic plasma exchange (TPE) and immunoadsorption (IA) have been recognized as two options for treating MS relapses, that do not respond to standard treatment with corticosteroids. TPE is already incorporated in most international guidelines, although evidence for its use resulted mostly from either case series or small unblinded and/or non-randomized trials. Data on IA are still sparse, but several studies indicate comparable efficacy between both apheresis procedures. This article gives an overview of the published evidence on TPE and IA in the treatment of acute relapses in MS. Further, we outline current evidence regarding individual outcome predictors, describe technical details of apheresis procedures, and discuss apheresis treatment in children and during pregnancy.
Development and validation of a clinical score to predict the probability of successful procedure in women undergoing external cephalic version

Abstract Introduction External Cephalic Version (ECV) reduces breech presentation at term and thus contribute to the reduction of cesarean section. This study was done to determine the factors associated with the successful ECV in women with breech presentation after 36 weeks’ gestation and also to develop and validate a clinical score which could be utilized for individual patient counseling in future. Methods This was a retrospective cohort study conducted in a tertiary care center and teaching hospital in south India. Prospectively collected data from the register maintained for all ECVs performed on pregnant women with breech presentation at or more than 36 weeks’ gestation. Clinical and ultrasound parameters at the time of performing the procedure were used in the analysis. Multiple logistic regression with a stepwise backward selection procedure was used selecting potential variable to construct the model and internal validation was done with bootstrapping. Primary outcome was successful ECV defined as cephalic presentation at the end of the procedure Results Among 611 women who underwent ECV, it was successful in 70.4%. In the multiple logistic regression model, multiparity (OR4.48), AFI ≥ 7 (OR = 3.06), type of breech, posterior placental location (OR = 1.57), sacro-anterior position of breech (OR = 2.83), normal uterine tone (OR = 1.82) and fetal pole not engaged (OR = 2.82) were found to be predictive of successful ECV with good discrimination (AUC = 0.782) and acceptable calibration. Combining these factors from the model a predictive score (score 0–13) is proposed for clinical utility. Conclusions Combining clinical and ultrasound parameters into a predictive score, which is simple and effective, could be utilized in the clinical practice, once validated externally.