Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism*

A mechanism for the cellular effects of the gas H2S, is the oxidative modification of protein cysteine residues. We developed a quantitative proteomics tool to profile protein S-persulfidation in cellular proteomes. We discovered a Redox Thiol Switch of S-glutathioinylation to S- persulfidation of proteins, among them enzymes in cellular energy metabolism. This work allows identification of redox regulation of cysteine residues of proteins in physiological and disease states and can assist design of therapeutics for diseases such cancer and diabetes. Graphical Abstract Highlights Develop a TMT-based proteomics tool to profile cysteine persulfides in the cellular proteomes. Discover a Redox Thiol Switch from protein S-glutathioinylation to S-persulfidation (RTSGS) with implications in the regulation of cellular energy metabolism under oxidative stress. The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H2S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H2S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTSGS). We propose that the RTSGS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.
Ultrasound in Hepatic Veno-occlusive Disease (HVOD) after Pediatric Hematopoietic Stem Cell Transplantation (HSCT): Comparison of Diagnostic Criteria Including the Pediatric Criteria of European Society for Blood and Marrow Transplantation (EBMT)

Abstract The European Society for Blood and Marrow Transplantation (EBMT) has recently announced new diagnostic criteria for pediatric hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). We retrospectively inspected 97 ultrasound exams of 60 pediatric HSCT patients, and compared its diagnostic value using the Baltimore, Seattle and pediatric EBMT criteria. Nine of the ten patients who were diagnosed as HVOD only in the EBMT criteria had severe or very severe HVOD. In the Seattle and EBMT criteria, portal vein velocity, peak systolic velocity and resistance index of hepatic artery, gallbladder wall thickening and ascites were statistically significant. No ultrasound variable showed significant association in the Baltimore criteria. All patients with portal vein velocity below 10 cm/s were in higher EBMT grade. A scoring system was developed, to evaluate the overall relationship of the ultrasound findings with the diagnosis of HVOD, showing fair (0.768 and 0.733) AUC in the ROC curve of EBMT and Seattle criteria.
Comparison Between Healthcare-Associated and Community-Acquired Infective Endocarditis at Tertiary Care Hospitals in Japan.

BACKGROUND Healthcare-associated infective endocarditis (HAIE) has become increasingly recognized worldwide because the underlying patient conditions are completely different from those of community-acquired infective endocarditis (CIE). However, data on HAIE in the Japanese population is lacking. We sought to clarify the patient characteristics and prognosis of HAIE in a Japanese population.Methods and Results:A retrospective study was conducted in 158 patients who were diagnosed with infective endocarditis, 53 of whom (33.5%) were classified as HAIE. Compared with patients with CIE, those with HAIE were older (median age 72 vs. 61 years; P=0.0002) and received surgical treatment less frequently (41.5% vs. 62.9%; P=0.01). Regarding causative microorganisms, staphylococci,including methicillin-resistant pathogens, were more common in patients with HAIE (32.1% vs. 14.3%; P=0.01). Patients with HAIE had higher in-hospital mortality (32.1% vs. 4.8%; P<0.0001) and Kaplan-Meier analysis showed worse prognosis for patients with HAIE than CIE (P<0.0001, log-rank test). On multivariate Cox analysis, HAIE (hazard ratio 3.26; 95% confidence interval 1.49-7.14), age ≥60 years, surgical treatment, stroke, and heart failure were independently associated with mortality. CONCLUSIONS HAIE has different clinical characteristics and causative microorganisms, as well as worse prognosis, than CIE. Preventive strategies, and the prompt and appropriate identification of HAIE may improve the outcome of infective endocarditis.
Alcohol-aggravated episodic pain in humans with SCN11A mutation and ALDH2 polymorphism.

Mutations in Nav1.9 encoded by SCN11A have been associated with episodic pain, small-fiber neuropathy and congenital insensitivity to pain. In this study, we collected and characterized one Chinese family with episodic pain. The SCN11A mutation (c.664C>A/p.Arg222Ser) was identified and cosegregated with the episodic pain phenotype. In addition, we found that alcohol intake triggered intense pain attacks and detected the ALDH2 polymorphism (c.1510G>A/p.Glu504Lys) in three patients with episodic pain. The alcohol-aggravated pain symptom and this ALDH2 polymorphism were also reconfirmed in our previously reported episodic pain patient with the Nav1.9 mutation (p.Ala808Gly, patient III-2 in HBBJ family). To assess the pathogenicity of the Nav1.9 mutation and the new trigger, we introduced a mutation (p.Ala796Gly) into the mouse (orthologous mutation in human is p.Ala808Gly). The alteration hyperpolarized channel activation, increased the residual current through non-inactivating channels, and induced hyperexcitability of dorsal root ganglion (DRG) neurons in Scn11a mice. The Scn11a mice showed increased sensitivity to mechanical, heat and cold stimuli, and hypersensitivity to acetaldehyde and formalin, which could account for the alcohol intake-induced pain phenotype in patients. Moreover, acetaldehyde increased the mutant mNav1.9 channel current and excitability of Scn11a mouse DRG neurons. Parecoxib (an anti-inflammatory medication) relieved the heat hypersensitivity in Scn11a mice not receiving inflammatory stimuli and significantly decreased the hyperexcitability of DRG neurons in Scn11a mice. These results indicated that Scn11a mice recapitulated many clinical features of patients and suggested that Nav1.9 channel contributes significantly to the inflammatory pain state.
Suggested Assessments for Sarcopenia in Patients With Stroke Who Can Walk Independently

Objective To investigate variables for assessment of stroke-related sarcopenia that are alternative options to the current assessment for sarcopenia, which focuses on age-related sarcopenia and also has limitations in addressing sarcopenia due to weakness resulting from stroke. Methods Forty patients (17 men, 23 women; mean age, 66.9±15.4 years) with first-ever stroke who can walk independently were included. Muscle mass was determined by measuring ultrasonographic muscle thickness of vastus intermedius, rectus femoris, tibialis anterior, medial gastrocnemius, and biceps brachii muscles in addition to using the skeletal muscle index (SMI) with bioelectrical impedance analysis. Muscle strength was assessed with the Medical Research Council (MRC) sum score as well as handgrip (HG) strength. Physical performance was measured by the Berg Balance Scale (BBS) along with 4-meter gait speed (4MGS). Correlations between each assessment in the three categories were analyzed and adjusted by stroke severity, comorbidity, and nutritional status. Results For muscle mass, SMI showed the highest correlation with the tibialis anterior muscle (r=0.783, p<0.001) among the other muscles. Regarding muscle strength, the MRC sum score correlated with the HG (r=0.660, p<0.001). For physical performance, the BBS correlated with the 4MGS (r=0.834, p<0.001). The same result was obtained after adjusting for factors of stroke severity, comorbidity, and nutritional status. Conclusion These results suggest that ultrasonographic muscle thickness of the tibialis anterior, the MRC sum score, and BBS might be alternatives to SMI, HG, and usual gait speed for sarcopenia in stroke patients.
Mobile Dental Delivery System: An Effective Protocol for Hygiene and Disinfection

Mobile dental delivery systems (MDDSs) are receiving growing interest for reaching isolated patients, as well as in dental care for fragile and hospitalized patients, with the advantage of being able to be used from room to room or during general anesthesia (GA) in an operating room. Therefore, ensuring the care safety is crucial. The aim of this study was to elaborate and assess an MDDS maintenance protocol, containing the management of dental unit waterlines and adapted to specific conditions such as dental care under GA. A step-by-step protocol was established and implemented for an MDDS used during dental care under GA in children. Samples of the output water were collected at J0, J+1, 3, 6, 12, and 24 months, and cultured to observe the microbiological quality of the water. All the results (heterotrophic plate count at 22 °C, at 37 °C, and specific pathogenic germs sought) showed an absence of contamination. The protocol presented was effective over time and allowed ensuring the safety of care to be ensured when using MDDS, even during dental procedures under GA. As a result, it could be implemented by any dental care delivery structure wanting to reinforce the safety of its practice.
Length-weight relationships of mesopelagic fishes from the equatorial and tropical Atlantic waters: influence of environment and body shape.

Length-weight relationships (LWR) were estimated for 36 mesopelagic fish species collected from the equatorial and tropical Atlantic encompassing several oceanographic regions: oligotrophic, equatorial, Cape Blanc, Cape Verde and the Canary Islands. The sample was composed of myctophids (25 specimens), gonostomatids (5), sternoptychids (3), stomiids (2) and phosichthyids (1). The species were clustered according to body shape: 'short and deep' (sternoptychids), 'elongate' (gonostomids, stomiids and some phosichthyids) and 'fusiform' (myctophids and some phosichthyids). Three types of weight and LWRs were considered: wet weight (WW), eviscerated wet weight (eWW) and eviscerated dry weight (eDW). The study demonstrated that most species present a positive allometric growth, independent of the weigh used. However, the allometric value varied in 40-50% of species depending on the type of weight considered. Significant variations linked to fish morphology were found in the relationship between the slope and intercept of the LWR equation. Significant differences were also noted in the water content linked to fish body shape. Based on the distributions of several species we compare their fitness between oceanographic regions using the relative condition factor (Krel ). Except for Diaphus brachycephalus (oligotrophic vs equatorial waters) and Lampanyctus alatus (equatorial, Cape Blanc, Cape Verde and the Canary Islands), no regional significant differences were observed in the species analysed. This article is protected by copyright. All rights reserved.
Multicenter Evaluation of the QIAstat-Dx Respiratory Panel for Detection of Viruses and Bacteria in Nasopharyngeal Swab Specimens

The QIAstat-Dx Respiratory Panel (QIAstat-Dx RP) is a multiplex in vitro diagnostic test for the qualitative detection of 20 pathogens directly from nasopharyngeal swab (NPS) specimens. The assay is performed using a simple sample-to-answer platform with results available in approximately 69 min. The pathogens identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus A and B, influenza A, influenza A H1, influenza A H3, influenza A H1N1/2009, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, rhinovirus/enterovirus, respiratory syncytial virus A and B, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. ABSTRACT The QIAstat-Dx Respiratory Panel (QIAstat-Dx RP) is a multiplex in vitro diagnostic test for the qualitative detection of 20 pathogens directly from nasopharyngeal swab (NPS) specimens. The assay is performed using a simple sample-to-answer platform with results available in approximately 69 min. The pathogens identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus A and B, influenza A, influenza A H1, influenza A H3, influenza A H1N1/2009, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, rhinovirus/enterovirus, respiratory syncytial virus A and B, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. This multicenter evaluation provides data obtained from 1,994 prospectively collected and 310 retrospectively collected (archived) NPS specimens with performance compared to that of the BioFire FilmArray Respiratory Panel, version 1.7. The overall percent agreement between QIAstat-Dx RP and the comparator testing was 99.5%. In the prospective cohort, the QIAstat-Dx RP demonstrated a positive percent agreement of 94.0% or greater for the detection of all but four analytes: coronaviruses 229E, NL63, and OC43 and rhinovirus/enterovirus. The test also demonstrated a negative percent agreement of ≥97.9% for all analytes. The QIAstat-Dx RP is a robust and accurate assay for rapid, comprehensive testing for respiratory pathogens.
Outcome of vitrectomy for advanced proliferative vitreoretinopathy complicating primary rhegmatogenous retinal detachment among Nigerians

Aim: To present the anatomical and visual outcome and compare different techniques in the surgical treatment of proliferative vitreoretinopathy (PVR) in Nigerians.Method: Comparative retrospective review of PVR grade C and D eyes that had vitreoretinal surgery with silicone oil between April 2005 and December 2012. Data was extracted from consecutive case notes after exclusion of eyes with PVR associated with proliferative diabetic retinopathy (PDR), proliferative sickle cell retinopathy (PSCR) and eyes with nonuse of silicone oil. A comparison of the outcome of vitrectomy alone (Vit.), versus combined with a scleral buckle (Vit.+SB), versus with retinectomy (Vit.+RT), versus with all three procedures (Vit.+SB+RT) was done. Statistical analysis was done using the Statistical Package for Social Sciences version 16 software. Pearson Chi-square test and Fisher's exact T-test were used to determine the effect of relationships. Results: 138 eyes of 138 patients had grades C (100 eyes) and grade D (38 eyes) PVR. Surgery involved vitrectomy and membrane peel in 53% of eyes, additional scleral buckle in 22%, and retinectomy was performed in 17%. Retinal reattachment rate was 86% for PVR C eyes and 87% in PVR D eyes. There was no statistically significant difference in anatomical outcome between vitrectomy alone and the combination surgeries. In the vitrectomy only category, the postoperative vision was noted to improve (> preoperative), in 48% of PVR C and in 31% of PVR D. 33% of PVR C and 44% of PVR D eyes had a worse vision (< preoperative). Visual outcome was similarly poor in the combination surgeries with improved vision noted in 12%, 44%, and 33% of the Vit. +SB, Vit. +RT, and Vit. +SB+RT PVR C eyes, respectively. In PVR D eyes, improved vision was seen in 57% and 12% of Vit. +SB and Vit. +RT eyes, respectively. Conclusion: Surgery results in anatomical reattachment and there is nonsuperiority of any technique. Visual outcome is poor as previously reported. Recent trials of pharmacological adjuncts may show promise for improved visual outcomes.
Relational processing demands and the role of spatial context in the construction of episodic simulations.

Reports on differences between remembering the past and imagining the future have led to the hypothesis that constructing future events is a more cognitively demanding process. However, factors that influence these increased demands, such as whether the event has been previously constructed and the types of details comprising the event, have remained relatively unexplored. Across two experiments, we examined how these factors influence the process of constructing event representations by having participants repeatedly construct events and measuring how construction times and a range of phenomenological ratings changed across time points. In Experiment 1, we contrasted the construction of past and future events and found that, relative to past events, the constructive demands associated with future events are particularly heightened when these events are imagined for the first time. Across repeated simulations, future events became increasingly similar to past events in terms of construction times and incorporated detail. In Experiment 2, participants imagined future events involving two memory details (person, location) and then reimagined the event either (a) exactly the same, (b) with a different person, or (c) in a different location. We predicted that if generating spatial information is particularly important for event construction, a change in location will have the greatest impact on constructive demands. Results showed that spatial context contributed to these heightened constructive demands more so than person details, consistent with theories highlighting the central role of spatial processing in episodic simulation. We discuss the findings from both studies in the light of relational processing demands and consider implications for current theoretical frameworks. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Co-delivery of brinzolamide and miRNA-124 by biodegradable nanoparticles as a strategy for glaucoma therapy

Abstract Co-delivery nanoparticles with characteristics of intracellular precision release drug have been generally accepted as an effective therapeutic strategy for eye diseases. In this study, we designed a new co-delivery system (miRNA/NP-BRZ) as a lasting therapeutic approach to prevent the neuro-destructive after the long-term treatment of glaucoma. Neuroprotective and intraocular pressure (IOP) response were assessed in in vivo and in vitro models of glaucoma. At the meaning time, we describe the preparation of miRNA/NP-BRZ, drug release characteristics, intraocular tracing, pharmacokinetic and pharmacodynamics study and toxicity test. We found that miRNA/NP-BRZ could remarkably decrease IOP and significantly prevent retinal ganglion cell (RGC) damages. The new formula of miRNA-124 encapsulated in PEG-PSA-BRZ nanoparticles exhibits high encapsulation efficiency (EE), drug-loading capacity (DC), and stable controlled-release efficacy (EC). Moreover, we also verified that the miRNA/NP-BRZ system is significantly neuroprotective and nontoxic as well as lowering IOP. This study shows our co-delivery drug system would have a wide potential on social and economic benefits for glaucoma.
The Relationship between Emotional Intelligence and Psychological Well-Being among Male University Students: The Mediating Role of Perceived Social Support and Perceived Stress

This study aimed to examine the subject of emotional intelligence (EI), which has received increased attention from scholars over the past few decades. The study utilized a quantitative longitudinal approach to attain the objective of understanding the correlation between EI and psychological well-being. A sample consisting of only male students was sought in this study in a process that was guided by specific criteria. The study reveals that students’ EI correlates positively with perceived social support and well-being at each time and across times. Negative relations are found between perceived stress and well-being at each time and across times. Results and findings reported in this study reveal that perceived social support partially mediates the longitudinal association between EI and well-being. Specifically, perceived stress does not mediate the longitudinal association between EI and well-being.
A murine model of Staphylococcus aureus infected chronic diabetic wound: A new tool to develop alternative therapeutics

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL‐17A compared to control mice that resulted in an IL‐17/IFN‐γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL‐10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL‐10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL‐10/IFN‐γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.