Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO.
DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial

BACKGROUND RV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein). METHODS One hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit. RESULTS All regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%–100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%–100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. CD4+ T cell responses were detectable in all treatment groups (32%–64%) without appreciable CD8+ T cell responses. CONCLUSION The DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2–binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses. TRIAL REGISTRATION ClinicalTrials.gov NCT02207920. FUNDING National Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845).
Ginseng aqueous extract ameliorates lambda‐cyhalothrin‐acetamiprid insecticide mixture for hepatorenal toxicity in rats: Role of oxidative stress‐mediated proinflammatory and proapoptotic protein expressions

This study was carried out to evaluate the protective effects of Panax ginseng aqueous extract (GAE) against hepatorenal toxicity induced by lambda‐cyhalothrin‐acetamiprid insecticide mixture in rats. A total of 32 male albino rats were assigned into four groups. Normal control group received distilled water. Insecticide control group intoxicated with the insecticide at a dose of 2.14 mg/kg b.wt orally day after day for 45 days. GAE control group was treated with GAE at a dose 200 mg/kg b.wt orally. GAE experimental group was administered GAE 1 hour before insecticide administration. Intoxication of rats with the insecticide caused a significant increase in serum aspartate aminotransferase and alanine aminotransferase activities and urea and creatinine levels as well as malondialdehyde concentration and proteins expression of caspase‐3 and induced nitric oxide synthase in hepatic and renal tissues. However, it decreased the serum levels of total protein and globulin and reduced the glutathione content and catalase activity in hepatic and renal tissues. In addition, insecticide induced histopathological alterations in both hepatic and renal tissues. In contrast, GAE modulated insecticide‐induced alterations in liver and kidney functions and structures as it ameliorated the effects of insecticide on the above mentioned parameters. These results indicated that GAE was a potent antioxidant agent that could protect rats against insecticide‐induced hepatorenal toxicity.
Obstetric and perinatal outcomes in pregnant women with Takayasu’s arteritis: single centre experience over five years

Objective: To study obstetric and perinatal outcomes among pregnant women with Takayasu arteritis (TA), attending our hospital for pregnancy and childbirth between January 2011 to December 2016. Material and Methods: Retrospective study was carried out by abstracting clinical charts on all pregnant women with TA who underwent antenatal care and/or delivery in our hospital during this period. American College of Rheumatology criteria was used for diagnosis of TA. Sixteen women with TA were included in the study. Maternal demographic data, stage of disease, complications related to disease, details of treatment taken prior to pregnancy, pregnancy outcomes, and neonatal outcomes were studied. Results: Forty-four percentage (7/16) belonged to type 5 angiographic type, however the same proportion (7/16) had undergone surgical corrections prior to pregnancy and the majority (15/16) were on medical management. Only three women (19%) were diagnosed during pregnancy. Most did not have active disease measured by Kerr’s criteria (n=12; 75%), and Indıan Takayasu clinical activity scores A. Chronic hypertension was the commonest antenatal complication (56.2%), nearly one-third had growth restricted babies and 25% had preterm labour. There were no cardiovascular events, no maternal deaths, nor fetal or neonatal deaths. Two-thirds of our women were delivered by caesarean section. Conclusion: Preconceptional counselling is of paramount importance in women with TA. Good maternal and fetal outcomes are observed with close antenatal surveillance and multidisciplinary care. Pregnancy should be planned during disease remission, with good antenatal care, close monitoring of clinical symptoms, early diagnosis and treatment of complications.
Normative values for region‐specific colonic and gastrointestinal transit times in 111 healthy volunteers using the 3D‐Transit electromagnet tracking system: Influence of age, gender, and body mass index

The 3D‐Transit electromagnet tracking system (Motilis Medica, SA, Lausanne, Switzerland) is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit and motility. Using this tool, we aimed to derive normative values for region‐specific colonic and GI transit times and to assess the influence of age, gender, and body mass index (BMI).
Pharmacology and social media: Potentials and biases of web forums for drug mention analysis—case study of France

The aim of this study is to analyze drug mentions in web forums to evaluate the utility of this data source for drug post-marketing studies. We automatically annotated over 60 million posts extracted from 21 French web forums. Drug mentions detected in this corpus were matched to drug names in a French drug database (Theriaque®). Our analysis showed that a high proportion of the most frequent drug mentions in the selected web forums correspond to drugs that are usually prescribed to young women, such as combined oral contraceptives. The most mentioned drugs in our corpus correlated weakly to the most prescribed drugs in France but seemed to be influenced by events widely reported in traditional media. In this article, we conclude that web forums have high potential for post-marketing drug-related studies, such as pharmacovigilance, and observation of drug utilization. However, the bias related to forum selection and the corresponding population representativeness should always be taken into account.
High pressure shifts the β1-adrenergic receptor to the active conformation in the absence of G protein.

G protein-coupled receptors (GPCRs) are versatile chemical sensors, which transmit the signal of an extracellular binding event across the plasma membrane to the intracellular side. This function is achieved via the modulation of highly dynamical equilibria of various conformational receptor states. Here we have probed the effect of pressure on the conformational equilibria of a functional thermostabilized β1-adrenergic GPCR (β1AR) by solution NMR. High pressure induces a large shift in the conformational equilibrium (midpoint ~600 bar) from the preactive conformation of agonist-bound β1AR to the fully active conformation, which under normal pressure is only populated when a G protein or a G protein-mimicking nanobody (Nb) binds to the intracellular side of the β1AR∙agonist complex. No such large effects are observed for an antagonist-bound β1AR or the ternary β1AR∙agonist∙Nb80 complex. The detected structural changes of agonist-bound β1AR around the orthosteric ligand binding pocket indicate that the fully active receptor occupies an ~100 Å3 smaller volume than its preactive form. Most likely, this volume reduction is caused by the compression of empty (non-hydrated) cavities in the ligand binding pocket and the center of the receptor, which increases the ligand receptor interactions and explains the ~hundredfold affinity increase of agonists in the presence of G protein. The finding that isotropic pressure induces a directed motion from the preactive to the fully active GPCR conformation provides evidence of the high mechanical robustness of this important functional switch.
Robust RBM3 and β-klotho expression in developing neurons in the human brain

RNA binding motif 3 (RBM3) is a powerful neuroprotectant that inhibits neurodegenerative cell death in vivo and is a promising therapeutic target in brain ischemia. RBM3 is increased by the hormone fibroblast growth factor 21 (FGF21) in an age- and temperature-dependent manner in rat cortical neurons. FGF21 receptor binding is controlled by the transmembrane protein β-klotho, which is mostly absent in the adult brain. We discovered that RBM3/β-klotho is unexpectedly high in the human infant vs. adult brain (hippocampus/prefrontal cortex). The use of tissue homogenates in that study precluded a comparison of RBM3/β-klotho expression among different CNS cell-types, thus, omitted key evidence (i.e. confirmation of neuronal expression) that would otherwise provide a critical link to support their possible direct neuroprotective effects in humans. This report addresses that knowledge gap. High-quality fixed human hippocampus, cortex, and hypothalamic tissues were acquired from the NIH Neurobiobank (<1 yr (premature born) infants, 1 yr, 4 yr, and 34 yr). Dual labeling of cell-type markers vs. RBM3/β-klotho revealed enriched staining of targets in neurons in the developing brain. Identifying that RBM3/β-klotho is abundant in neurons in the immature brain is fundamentally important to guide protocol design and conceptual frameworks germane to future testing of these neuroprotective pathways in humans.
A critical discourse analysis of gendered cardiovascular disease meanings of the #MoreMoments campaign on Twitter

The purpose of this study was to explore how the Heart and Stroke Foundation of Canada and Canadian Twitter users linked women’s experiences and health identities with the #MoreMoments cardiovascular disease awareness campaign. Critical discourse analysis of Twitter data between September 2017 and November 2017 identified two primary discourses (tragedy and loss, and life and health) and two identity/subject positions (visionary leaders and successful survivors). Responsibility for women’s health was attributed to the Heart and Stroke Foundation of Canada, also limiting neo-liberal healthism and risk identification. Novel findings included resistance through use of ‘small stories’ within discourses regarding the targeted demographic for health promotion and knowledge translation.
Weekly Drinking and Binge Drinking Mediate the Association Between Drinking Location and Sexual Coercion

It has been well documented that alcohol use is a risk factor for sexual assault. However, few studies have examined how alcohol use is associated with sexual coercion experiences. Furthermore, off-campus parties and bars are drinking locations where alcohol use is high among college students. It is important to determine other risk factors, such as the drinking location, that may affect alcohol use and sexual coercion. The current study examined whether alcohol use (drinks per week and binge drinking) mediated the association between drinking location frequency (off-campus party and bar/restaurant) and experiencing sexual coercion in the past 30 days. Participants were N = 295 young adult (Mage = 21.17 years, SD = 2.70) undergraduate women who reported drinking at least once in the past 30 days and completed an online survey. Results revealed that 88 (29.8%) participants experienced sexual coercion in the past 30 days. Participants who experienced sexual coercion in the past 30 days reported greater drinks per week, were more likely to binge drink, and reported drinking more frequently at off-campus parties than those who had not experienced sexual coercion. Drinks per week significantly mediated the relationship between drinking location frequency (off-campus party and bar/restaurant) and sexual coercion. Specifically, more frequent drinking at off-campus parties and bars/restaurants was associated with greater drinks per week, which in turn was related to experiencing sexual coercion in the past 30 days. Binge drinking significantly mediated the association between frequency of drinking at a bar/restaurant and sexual coercion, but not off-campus drinking frequency. Findings suggest that college student alcohol interventions that target harm reduction should consider including information about how the drinking location may intersect with alcohol use to increase risk for sexual coercion.
Automated Machine Learning Based on Radiomics Features Predicts H3 K27M Mutation in Midline Gliomas of the Brain.

BACKGROUND Conventional MRI cannot be used to identify H3 K27M mutation status. This study aimed to investigate the feasibility of predicting H3 K27M mutation status by applying an automated machine learning (autoML) approach to the MR radiomics features of patients with midline gliomas. METHODS This single-institution retrospective study included 100 patients with midline gliomas, including 40 patients with H3 K27M mutations and 60 wild-type patients. Radiomics features were extracted from FLAIR images. Prior to autoML analysis, the dataset was randomly stratified into separate 75% training and 25% testing cohorts. The Tree-based Optimization Tool (TPOT) was applied to optimize the machine learning pipeline and select important radiomics features. We compared the performance of ten independent TPOT-generated models based on training and testing cohorts using the area under the curve (AUC) and average precision to obtain the final model. An independent cohort of 22 patients was used to validate the best model. RESULTS Ten prediction models were generated by TPOT, and the accuracy obtained with the best pipeline ranged from 0.788 to 0.867 for the training cohort and from 0.60 to 0.84 for the testing cohort. After comparison, the AUC value and average precision of the final model were 0.903 and 0.911 in the testing cohort, respectively. In the validation set, the AUC was 0.85, and the average precision was 0.855 for the best model. CONCLUSIONS The autoML classifier using radiomics features of conventional MR images provides high discriminatory accuracy in predicting the H3 K27M mutation status of midline glioma.
Auditory Object Segregation: Investigation Using Computer Modelling and Empirical Event-Related Potential Measures

There are multiple factors that influence auditory steaming. Some, like frequency separation or rate of presentation, have effects that are well understood while others remain contentious. Human behavioural studies and event-related potential (ERP) studies have shown dissociation between a pre-attentive sound segregation process and an attention-dependent process in forming perceptual objects and streams. This thesis first presents a model that synthetises the processes involved in auditory object creation. It includes sensory feature extraction based on research by Bregman (1990), sensory feature binding through an oscillatory neural network based on work by Wang (1995; 1996; 1999; 2005; 2008), work by Itti and Koch (2001a) for the saliency map, and finally, work by Wrigley and Brown (2004) for the architecture of single feature processing streams, the inhibition of return of the activation and the attentional leaky integrate and fire neuron. The model was tested using stimuli and an experimental paradigm used by Carlyon, Cusack, Foxton and Robertson (2001). Several modifications were then implemented to the initial model to bring it closer to psychological and cognitive validity. The second part of the thesis furthers the knowledge available concerning the influence of the time spent attending to a task on streaming. Two deviant detection experiments using triplet stimuli are presented. The first experiment is a follow-up of Thompson, Carlyon and Cusack (2011) and replicated their behavioural findings, showing that the time spent attending to a task enhances streaming, and that deviant detection is easier when one stream is perceived. The ERP results showed double decisions markers indicating that subjects may have made their deviant detection based on the absence of the time delayed deviant and confirmed their decision with its later presence. The second experiment investigated the effect of the time spent attending to the task in presence of a continuity illusion on streaming. It was found that the iv AUDITORY OBJECT SEGREGATION: MODEL AND ERP MEASURES presence of this illusion prevented streaming in such a way that the pattern of the triplet was strengthened through time instead of separated into two streams, and that the deviant detection was easier the longer the subjects attended to the sound sequence. v AUDITORY OBJECT SEGREGATION: MODEL AND ERP MEASURES
Effects of a Self-Compassion Break Induction on Self-Reported Stress, Self-Compassion, and Depressed Mood

Introduction The objective of the study was to determine whether practicing a self-compassion induction would reduce self-reported stress, depressed mood, and increase self-compassion in a randomized controlled study measuring variables of interest at two time points spanning three weeks. Method Participants were 129 students (91 females and 38 males, Mage = 19.47, SD = 3.20) divided into three groups: Self-compassion Break, Time Management Control Group, and a No-Induction Control Group. Participants were part of the general student body and were not diagnosed or screened for clinical depression. Self-compassion, stress, and depressed mood were assessed at baseline and follow-up. Participants practiced their respective inductions over three weeks after being guided through their respective inductions at Time 1. Results There were no significant differences between groups in outcome variables. Results of this study may indicate the importance of weekly group check-in meetings to facilitate positive change as findings in this study did not mirror those of similar studies using frequent meetings.
Proteobacteria Acts as a Pathogenic Risk-Factor for Chronic Abdominal Pain and Diarrhea in Post-Cholecystectomy Syndrome Patients: A Gut Microbiome Metabolomics Study

Background Laparoscopic cholecystectomy (LC) is regarded as the criterion standard for gallstone therapy, but post-cholecystectomy syndrome (PCS) is a common complication. This study aimed to analyze and identify differences in gut microbiome in PCS patients. Material/Methods This study involved 8 PCS patients (RS1), 8 asymptomatic PCS patients (RS2), and 8 healthy individuals (RS3). Genomic DNA of gut microbiome was extracted and amplified with CTAB method. PCR products were sequenced with Illumina High-Through Sequencing. Sequencing data were analyzed with QIIME software. Effective sequence of bacterial 16S-rRNA gene was clustered into OTUs using UPARSE software. Species annotations were evaluated using Mothur software. QIIME software was used to conduct complexity analysis and calculate UniFrac distances. R software was used to generate PCoA plots. Results Bacterial 16S-rDNA gene sequences showed that the effective species annotative data were more than 97%. According to Ternary plot, Firmicutes and Bacteroidetes had similar abundance and contents among the 3 groups. Contents of Proteobacteria in RS1 were higher compared to RS2 and RS3. Bacterial genomic DNAs samples were clustered together in the same group; however, distances were relative far between different groups. RS1 illustrated significantly higher abundance of Proteobacteria colonies compared to healthy people (p<0.05), and illustrated higher abundance of Verrucomicrobia and lower abundance of Bacteroidetes and Firmicutes, but without significant differences (p>0.05). Conclusions Gut microbiome of PCS patients was dominated by Proteobacteria in feces and contained little Firmicutes and Bacteroidetes. The enhanced abundance of Proteobacteria might be the highly pathogenic risk factor for chronic abdominal pain and diarrhea in PCS patients.
Altmetric analysis of the contemporary scientific literature in Endodontology.

AIM To analyze and visualize the knowledge structure of scientific articles in the field of Endodontology with high altmetric attention scores to discover hot topics, active researchers and which journals were involved. METHODOLOGY On 5 June 2019 the altmetric database (Altmetric LLP, London, UK) was searched using the titles of 11 endodontic journals. Bibliometric data from endodontic articles and journals with an altmetric score>5 (top 5%) were retrieved from PubMed and analyzed using the VOSviewer. Science mapping of articles with an altmetric score>5 at two levels was created: author keywords co-occurrence and co-authorship network analysis. RESULTS Of the 2197 articles in the field of Endodontology identified with altmetrics, 192 had altmetric scores>5 (top 5%). Considering the total mentions among all altmetric resources, the Journal of Endodontics had the highest rank followed by the International Endodontic Journal and Australian Endodontic Journal. Twitter was the most popular altmetric data resource followed by patents andFacebook. Meta-analysis, systematic review and pulpitiswere the hot topics. At the author level, Dummer P.M. H had the greatest influence on the network. There was no significant correlation between altmetric score and citations count (P>0.05). Mendeley mentions correlated with citations (P<0.05). CONCLUSIONS Overall, the altmetric scores of topics within Endodontology were low, possibly due to the specific and specialized nature of the specialty, as well as the difficulty members of the public probably have in understanding endodontic research. Journals and researchers with a focus on Endodontology would have more influence if they were to set-up their own social media profiles and thus enhance their visibility and social impact by immediately sharing research findings and communicating with their network and audience.