Miracle-dz/UniFAR-FTUs huggingface dataset:
Stabilization of the V2 loop improves the presentation of V2 loop–associated broadly neutralizing antibody epitopes on HIV-1 envelope trimers

A successful HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs) that target the envelope glycoprotein (Env) spike on the virus. Native-like recombinant Env trimers of the SOSIP design now serve as a platform for achieving this challenging goal. However, SOSIP trimers usually do not bind efficiently to the inferred germline precursors of bNAbs (gl-bNAbs). We hypothesized that the inherent flexibilities of the V1 and V2 variable loops in the Env trimer contribute to the poor recognition of gl-bNAb epitopes at the trimer apex that extensively involve V2 residues. To reduce local V2 flexibility and improve the binding of V2-dependent bNAbs and gl-bNAbs, we designed BG505 SOSIP.664 trimer variants containing newly created disulfide bonds intended to stabilize the V2 loop in an optimally antigenic configuration. The first variant, I184C/E190C, contained a new disulfide bond within the V2 loop, whereas the second variant, E153C/R178C, had a new disulfide bond that cross-linked V2 and V1. The resulting engineered native-like trimer variants were both more reactive with and were neutralized by V2 bNAbs and gl-bNAbs, a finding that may be valuable in the design of germline targeting and boosting trimer immunogens to create an antigenic conformation optimal for HIV vaccine development.
Multiframe Ultrasonic TOFD Weld Inspection Imaging Based on Wavelet Transform and Image Registration

TOFD (time of flight diffraction) is a kind of weld defect detection technology by using ultrasonic diffraction wave signal. Because the diffraction intensity is far less than ultrasonic echo wave intensity, thus, the noise contained in TOFD signal is fairly large, and the formed image is not clear enough. Therefore, it is difficult to determine the size of defects accurately. In this paper, a method of noise reduction of TOFD signal and improving the resolution of the image are discussed based on the combination of wavelet thresholding and image registration. Wavelet multiresolution analysis method is adopted and the A-scan signal is decomposed into different frequency components. We propose a new threshold function to process the wavelet coefficients, which guarantees to denoise while preserving the useful information as much as possible. Setting up the ultrasonic TOFD inspection system and the image data with randomly distributed noise can be obtained via fine shake of the probes during testing. Then, image registration based on maximum correlation and blending is adopted to eliminate the noise in further step. The result shows that the proposed method can achieve denoising, together with resolution enhancement.
Specific, Sensitive, and Stable Reporting of Human Mesenchymal Stromal Cell Chondrogenesis.

IMPACT STATEMENT The promoter characterized in this study has been made accessible as a resource for the skeletal tissue engineering and regenerative medicine community. When combined with suitable reporter vectors, the resulting tools can be used for noninvasive and/or high-throughput screening of test conditions for stimulating chondrogenesis by candidate stem/progenitor cells. As demonstrated in this study, they can also be used with small animal imaging platforms to monitor the chondrogenic activity of implanted progenitors within orthotopic models of bone and cartilage repair.
Relationship between Fluoride Concentration and Activity against Virulence Factors and Viability of a Cariogenic Biofilm: in vitro Study

Despite widespread use of various concentrations of fluoride for the prevention of dental caries, the relationship between fluoride concentration and activity against cariogenic biofilms has not been much studied. Herein we investigated the relationship between fluoride concentration and activity against virulence factors and viability of Streptococcus mutans biofilms. S. mutans biofilms were formed on saliva-coated hydroxyapatite discs. The 70-hour-old biofilms were exposed to 0, 1, 3, 10, 30, 100, 300, 1,000 or 2,000 ppm F-. The changes of virulence factors and viability of the biofilms were analyzed using biochemical methods and laser scanning confocal fluorescence microscopy. At 1-2,000 ppm F-, the activity of fluoride against acid production, acid tolerance, and extracellular polysaccharide formation of S. mutans biofilms accurately followed a sigmoidal pattern of concentration dependence (R2 = 0.94-0.99), with EC50 values ranging from 3.07 to 24.7 ppm F-. Generally, the activity of fluoride against the virulence factors was concentration-dependently augmented in 10-100 ppm F- and did not increase further at concentrations higher than 100 ppm F-. However, fluoride did not alter glucosyltransferase activity and viability of S. mutans biofilm cells in all concentrations tested. These results can provide a basis for the selection of appropriate fluoride concentrations that reduce the physiological ability of cariogenic biofilms.
Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold

Owing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT‐MSCs), and after characterization cultured on the PES‐PANI scaffold and culture plate. Electron microscopic and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT‐MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real‐time reverse‐transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT‐MSCs was significantly increased when grown on PES‐PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES‐PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.
The co-chaperone UNC45A is essential for the expression of mitotic kinase NEK7 and tumorigenesis

Cumulative evidence suggests that the heat shock protein 90 (Hsp90) co-chaperone UNC-45 myosin chaperone A (UNC45A) contributes to tumorigenesis and that its expression in cancer cells correlates with proliferation and metastasis of solid tumors. However, the molecular mechanism by which UNC45A regulates cancer cell proliferation remains largely unknown. Here, using siRNA-mediated gene silencing and various human cells, we report that UNC45A is essential for breast cancer cell growth, but is dispensable for normal cell proliferation. Immunofluorescence microscopy, along with gene microarray and RT-quantitative PCR analyses, revealed that UNC45A localizes to the cancer cell nucleus, where it up-regulates the transcriptional activity of the glucocorticoid receptor and thereby promotes expression of the mitotic kinase NIMA-related kinase 7 (NEK7). We observed that UNC45A-deficient cancer cells exhibit extensive pericentrosomal material disorganization, as well as defects in centrosomal separation and mitotic chromosome alignment. Consequently, these cells stalled in metaphase and cytokinesis and ultimately underwent mitotic catastrophe, phenotypes that were rescued by heterologous NEK7 expression. Our results identify a key role for the co-chaperone UNC45A in cell proliferation and provide insight into the regulatory mechanism. We propose that UNC45A represents a promising new therapeutic target to inhibit cancer cell growth in solid tumor types.
Insulin immuno-neutralization decreases food intake in chickens without altering hypothalamic transcripts involved in food intake and metabolism

&NA; In mammals, insulin regulates blood glucose levels and plays a key regulatory role in appetite via the hypothalamus. In contrast, chickens are characterized by atypical glucose homeostasis, with relatively high blood glucose levels, reduced glucose sensitivity of pancreatic beta cells, and large resistance to exogenous insulin. The aim of the present study was to investigate in chickens the effects of 5 h fasting and 5 h insulin immuno‐neutralization on hypothalamic mRNA levels of 23 genes associated with food intake, energy balance, and glucose metabolism. We observed that insulin immune‐neutralization by administration of anti‐porcine insulin guinea pig serum (AI) significantly decreased food intake and increased plasma glucose levels in chickens, while 5 h fasting produced a limited and non‐significant reduction in plasma glucose. In addition, 5 h fasting increased levels of NPY, TAS1R1, DIO2, LEPR, GLUT1, GLUT3, GLUT8, and GCK mRNA. In contrast, AI had no impact on the levels of any selected mRNA. Therefore, our results demonstrate that in chickens, food intake inhibition or satiety mechanisms induced by insulin immuno‐neutralization do not rely on hypothalamic abundance of the 23 transcripts analyzed. The hypothalamic transcripts that were increased in the fasted group are likely components of a mechanism of adaptation to fasting in chickens.
Greater empathy in MDMA users

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes. Method: Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users (n = 25), poly-drug users who do not use MDMA (n = 19), alcohol-only users (n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task – a computerised assessment of empathy – and the Cyberball Game – a social exclusion paradigm. Results: MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy. Conclusions: Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.
Utility of FIB4-T as a Prognostic Factor for Hepatocellular Carcinoma

Background: Most integrated scores for predicting the prognosis of patients with hepatocellular carcinoma (HCC) comprise tumor progression factors and liver function variables. The FIB4 index is an indicator of hepatic fibrosis calculated on the basis of age, aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels, and platelet count, but it does not include variables directly related to liver function. We propose a new staging system, referred to as “FIB4-T,” comprising the FIB4 index as well as tumor progression factors, and examine its usefulness. Method: Subjects included 3800 cases of HCC registered in multiple research centers. We defined grades 1, 2, and 3 as a Fibrosis-4 (FIB4) index of <3.25, 3.26–6.70, and >6.70 as FIB4, respectively, and calculated the FIB4-T in the same manner in which the JIS (Japan Integrated Staging Score) scores and albumin-bilirubin tumor node metastasis (ALBI-T) were calculated. We compared the prognostic prediction ability of FIB4-T with that of the JIS score and ALBI-T. Results: Mean observation period was 37 months. The 5-year survival rates (%) of JIS score (0/1/2/3/4/5), ALBI-T (0/1/2/3/4/5) and FIB4-T (0/1/2/3/4/5) were 74/60/36/16/0, 82/66/45/22/5/0 and 88/75/65/58/32/10, respectively. Comparisons of the Akaike information criteria among JIS scores, ALBI-T, and FIB4-T indicated that stratification using the FIB4-T system was comparable to those using ALBI-T and JIS score. The risk of mortality significantly increased (1.3–2.8 times/step) with an increase in FIB4-T, and clear stratification was possible regardless of the treatment. Conclusions: FIB4-T is useful in predicting the prognosis of patients with HCC from a new perspective.
Measurement of serum hepatitis B surface antibody levels in Iranian autistic children and evaluation of immunological memory after booster dose injection in comparison with controls

Responsiveness to hepatitis B vaccine among patients with autism spectrum disorders (ASD) has not been evaluated worldwide. We aimed to determine the anti‐HBs antibody duration in autistic and healthy children few years after primary vaccination and evaluate their immunological memory against hepatitis B virus (HBV) vaccine with booster dose administration.
Effect of a Carbohydrate-Electrolyte Solution on Fluid Balance and Performance at a Thermoneutral Environment in International-Level Fencers.

Chryssanthopoulos, C, Tsolakis, C, Bottoms, L, Toubekis, A, Zacharogiannis, E, Pafili, Z, and Maridaki, M. Effect of a carbohydrate-electrolyte solution on fluid balance and performance at a thermoneutral environment in international-level fencers. J Strength Cond Res XX(X): 000-000, 2019-The purpose of the study was to examine a possible effect of a carbohydrate-electrolyte (CHO-E) solution on fluid balance and performance in fencing at a thermoneutral environment. Sixteen fencers performed two 120-minute training sessions separated by 7-14 days under similar environmental conditions (temperature: 20.3° C and humidity: 45-47%). Each session consisted of 60-minute conditioning exercises followed by 10 bouts of 3 minutes against the same opponent with 3-minute interval between each bout. Participants ingested at regular intervals either a 6% CHO-E solution or an artificially sweetened water (PL) in a counterbalanced order. No difference was observed between conditions in the heart rate responses, perceived exertion, changes in plasma volume, urine specific gravity, number of bouts won or lost, or points for and against. Considerable variability was observed in body mass changes that revealed significant differences at the time level (i.e., pre- vs. post-exercise) (F1,15 = 9.31, p = 0.008, η = 0.38), whereas no difference was found between conditions (i.e., CHO-E vs. PL) (F1,15 = 0.43, p = 0.52, η = 0.03) and conditions × time interaction (F1,15 = 3.57, p = 0.078, η = 0.19). Fluid loss was not significantly different between conditions (p = 0.08, d = 0.47). The blood glucose level was higher (p < 0.01) after exercise in CHO-E, whereas the blood lactate level was similar between conditions. In conclusion, the CHO-E solution was as effective as the artificially sweetened water in terms of fluid balance and fencing performance at a thermoneutral environment. Because of large individual variability, fencers should monitor their fluid intake and body fluid loss in training and competition.
Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma

Purpose: A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)–engineered, autologous primary human CD8+ cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). Experimental Design: Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8+ CTL targeting IL13Rα2. Patients received up to 12 local infusions at a maximum dose of 108 CAR-engineered T cells via a catheter/reservoir system. Results: We demonstrate the feasibility of manufacturing sufficient numbers of autologous CTL clones expressing an IL13(E13Y)-zetakine CAR for redirected HLA-independent IL13Rα2-specific effector function for a cohort of patients diagnosed with GBM. Intracranial delivery of the IL13-zetakine+ CTL clones into the resection cavity of 3 patients with recurrent disease was well-tolerated, with manageable temporary brain inflammation. Following infusion of IL13-zetakine+ CTLs, evidence for transient anti-glioma responses was observed in 2 of the patients. Analysis of tumor tissue from 1 patient before and after T-cell therapy suggested reduced overall IL13Rα2 expression within the tumor following treatment. MRI analysis of another patient indicated an increase in tumor necrotic volume at the site of IL13-zetakine+ T-cell administration. Conclusions: These findings provide promising first-in-human clinical experience for intracranial administration of IL13Rα2-specific CAR T cells for the treatment of GBM, establishing a foundation on which future refinements of adoptive CAR T-cell therapies can be applied. Clin Cancer Res; 21(18); 4062–72. ©2015 AACR.
Patient and facility characteristics associated with benzodiazepine prescribing for veterans with PTSD.

OBJECTIVE Practice guidelines used in the Veterans Health Administration (VHA) caution against benzodiazepine use by veterans with posttraumatic stress disorder (PTSD) because of inefficacy and safety concerns. Although use has declined, the VHA prescription rate is ≥30% nationally. To inform intervention design, this study examined patient- and facility-level correlates of benzodiazepine prescribing. METHODS This cross-sectional study used 2009 national administrative VHA data to identify veterans with PTSD, benzodiazepine prescriptions, and various patient and facility characteristics. Correlates of benzodiazepine prescribing were determined with multivariable hierarchical logit models. RESULTS Among 137 VHA facilities, 495,309 veterans with PTSD were identified, and 150,571 (30.4%) received a benzodiazepine prescription. Patient characteristics independently associated with benzodiazepine use included female gender, age ≥30 years, rural residence, service-connected disability ≥50%, Vietnam-era service, duration of PTSD diagnosis, and a comorbid anxiety disorder. However, case-mix adjustment for these variables accounted for <1% of prescribing variation. Facility characteristics independently associated with higher use included lower PTSD visit volume, higher rates of duplicate prescribing (concurrent use of more than one drug from a class), and lower rates of trazodone prescribing. These findings were corroborated in replication analyses. CONCLUSION The ultimate goal is to ensure consistent access to guideline-concordant PTSD treatment across the VHA. This study furthered this objective by identifying characteristics associated with benzodiazepine prescribing. Findings suggest that interventions could be designed to target individual high-volume prescribers or influence prescribing culture at the facility level.
The Effect of Electric Cross-Talk in Retinal Neurostimulation.

PURPOSE To investigate the efficacy of electric field shaping in modulating the extent and activation threshold in retinal neurostimulation. This study aims to quantify the interference of neighboring stimulation sites by assessing the shift in the activation threshold produced by a concomitant interfering stimulus. METHODS Electrical stimuli were applied to healthy retinae in a feline model (n = 4) using a 24-channel electrode array surgically implanted in the suprachoroidal space. A 96-channel penetrating electrode array was used for recording cortical responses to a number of stimulation paradigms. Data were analyzed offline. Concurrent monopolar and hexapolar stimuli were delivered at primary and interfering sites separated by up to 2.19 mm to evaluate electric cross-talk. The spike rate was fit to a sigmoidal curve to estimate the P50 threshold. The slope of the linear regression of the P50 value versus interfering current level was considered as a measure of cross-talk. RESULTS Concurrent monopolar stimulation produced a proportional drop in the P50 of approximately 20% of the interfering current level in presence of a primary monopolar and hexapolar stimulus. On the other hand, hexapolar interference did not alter activation thresholds at the primary site. CONCLUSIONS Hexapolar stimulation reduces electric cross-talk between neighboring sites and represents a technique to reduce interference between individual stimulation sites. In contrast, concurrent monopolar stimulation produces a reduction of the activation threshold of stimuli delivered nearby. Thus, a single source of subthreshold monopolar charge injection can provide benefit in the form of significant threshold reduction simultaneously at multiple stimulation sites.
A protocol for systematic review and meta-analysis

Background: Ventilator has been reported to treat acute respiratory distress syndrome (ARDS). However, its efficacy is still inconclusive. This systematic review andmeta-analysis study aims to evaluate its efficacy and safety for the treatment of patients with ARDS. Methods: The electronic databases of Cochrane central register of controlled trials (CENTRAL), EMBASE, MEDILINE, CINAHL, allied and complementary medicine database (AMED) and 4 Chinese databases will be used to search relevant literature from their inception to the present to evaluate the efficacy and safety of ventilator for ARDSwithout the language restrictions. This study will only consider randomized controlled trials (RCTs) of ventilator for the treatment of ARDS. The Cochrane risk of bias tool will be utilized to assess the quality of the included RCTs studies. The primary outcomes include arterial blood gases values (recorded once a day) and ventilator settings. The secondary outcomes will include the Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score, quality of life, cost, death, and any other adverse events. The summary results will be performed by using the models of random-effects or fixed-effects based on the heterogeneity of the included RCTs. Results: The results will be disseminated to peer-reviewed journals for publication. This study does not need ethics approval, because of no individual data will be involved. The results of this study will help clinicians and health policy-makers to refer for the policy or guideline making. Conclusion: The results of this systematic review and meta-analysis study may provide helpful evidence for the efficacy and safety of ventilator for ARDS. Systematic review registration: PROSPERO CRD42018 115409. Abbreviations: AMED = allied and complementary medicine database, ARDS = acute respiratory distress syndrome, CBM = Chinese biomedical literature database, CENTRAL = Cochrane central register of controlled trials, CINAHL = cumulative index to nursing and allied health literature, CIs = confidence intervals, CNKI = China national knowledge infrastructure, MD = mean difference, PRISMA-P = systematic reviews of interventions and the preferred reporting items for systematic reviews and metaanalysis protocol, RCTs = randomized controlled trials, RR = risk ratio, SMD = standardized mean difference, VIP = VIP Information, WANFANG = Wanfang data.