Miracle-dz/UniFAR-FTUs huggingface dataset:
National Institute on Drug Abuse genomics consortium white paper: Coordinating efforts between human and animal addiction studies

The National Institute on Drug Abuse Genetics and Epigenetics Cross‐Cutting Research Team convened a diverse group of researchers, clinicians, and healthcare providers on the campus of the University of California, San Diego, in June 2018. The goal was to develop strategies to integrate genetics and phenotypes across species to achieve a better understanding of substance use disorders through associations between genotypes and addictive behaviors. This conference (a) discussed progress in harmonizing large opioid genetics cohorts, (b) discussed phenotypes that are used for genetics studies in humans, (c) examined phenotypes that are used for genetics studies in animal models, (d) identified synergies and gaps in phenotypic analyses of human and animal models and (e) identified strategies to integrate genetics and genomics data with phenotypes across species. The meeting consisted of panels that focused on phenotype harmonization (Dr. Laura Bierut, Dr. Olivier George, Dr. Dan Larach and Dr. Sesh Mudumbai), translating genetic findings between species (Dr. Elissa Chesler, Dr. Gary Peltz and Dr. Abraham Palmer), interpreting and understanding allelic variations (Dr. Vanessa Troiani and Dr. Tamara Richards) and pathway conservation in animal models and human studies (Dr. Robert Hitzemann, Dr. Huda Akil and Dr. Laura Saba). There were also updates that were provided by large consortia (Dr. Susan Tapert, Dr. Danielle Dick, Dr. Howard Edenberg and Dr. Eric Johnson). Collectively, the conference was convened to discuss progress and changes in genome‐wide association studies.
Proteomic Analysis and Virulence Assessment of Granulicatella adiacens Secretome

Despite reports on the occurrence of Granulicatella adiacens in infective endocarditis, few mechanistic studies on its virulence characteristics or pathogenicity are available. Proteins secreted by this species may act as determinants of host-microbe interaction and play a role in virulence. Our aim in this study was to investigate and functionally characterize the secretome of G. adiacens. Proteins in the secretome preparation were digested by trypsin and applied to nanoLC-ESI-MS/MS. By using a combined mass spectrometry and bioinformatics approach, we identified 101 proteins. Bioinformatics tools predicting subcellular localization revealed that 18 of the secreted proteins possessed signal sequence. More than 20% of the secretome proteins were putative virulence proteins including serine protease, superoxide dismutase, aminopeptidase, molecular chaperone DnaK, and thioredoxin. Ribosomal proteins, molecular chaperones, and glycolytic enzymes, together known as “moonlighting proteins,” comprised fifth of the secretome proteins. By Gene Ontology analysis, more than 60 proteins of the secretome were grouped in biological processes or molecular functions. KEGG pathway analysis disclosed that the secretome consisted of enzymes involved in biosynthesis of antibiotics. Cytokine profiling revealed that secreted proteins stimulated key cytokines, such as IL-1β, MCP-1, TNF-α, and RANTES from human PBMCs. In summary, the results from the current investigation of the G. adiacens secretome provide a basis for understanding possible pathogenic mechanisms of G. adiacens.
Convolutional Neural Network and 2-D Image Based Fault Diagnosis of Bearing without Retraining

Bearings are vital part of rotary machines. A failure of bearing has a negative impact on schedules, production operation and even human casualties. Therefore, in prior achieving fault diagnosis of bearings is very important. How well features are extracted from vibration signals have a great influence on the performance of traditional intelligent fault diagnosis as well as it is important to achieve good performance without retraining under various operating conditions. However, it usually requires extensive domain expertise and prior knowledge. Instead of traditional machine learning algorithms, deep learning algorithms have a capacity of automatically learning the discriminative feature representation from input data effectively and accurately. So deep learning models can overcome drawbacks of traditional intelligent fault diagnosis. This paper will focus on converting vibration signals to vibration image and then we will use it for convolutional neural network (CNN) which we will use for fault diagnosis to learn features.
Human mutations highlight an intersubunit cation–π bond that stabilizes the closed but not open or inactivated states of TRPV channels

Significance Transient receptor potential (TRP) channels are key cation channels that respond to thermal, chemical, electric, or mechanical stimuli. There are >60 mutations known in TrpV4 that cause defects in bone or neural development. Two mutations guided us to examine a cation–π bond, which we found to tie the four subunits together to help close the channel gate. This or a similar bond is seen in many structures of TRP channels. In experiments, breaking this bond favors opening and inactivation of TRPV4. An adequate response of a living cell to the ever-changing environment requires integration of numerous sensory inputs. In many cases, it can be achieved even at the level of a single receptor molecule. Polymodal transient receptor potential (TRP) channels have been shown to integrate mechanical, chemical, electric, and thermal stimuli. Inappropriate gating can lead to pathologies. Among the >60 known TRP vanilloid subfamily (V) 4 mutations that interfere with bone development are Y602C or R616Q at the S4–S5 linker. A cation–π bond between the conservative residues Y602 and R616 of neighboring subunits appears likely in many homologous channel structures in a closed state. Our experiments with TRPV4 mutants indicate that the resting-closed state remains stable while the bond is substituted by a salt bridge or disulfide bond, whereas disruption of the contact by mutations like Y602C or R616Q produces gain-of-function phenotypes when TRPV4 is heterologously expressed in the Xenopus oocyte or yeast. Our data indicate that the Y602–R616 cation–π interactions link the four S4–S5 linker helices together, forming a girdle backing the closed gate. Analogous cation–π bonds and the girdle are seen in many closed TRP channel structures. This girdle is not observed in the cryo-EM structure of amphibian TRPV4 (Protein Data Bank ID code 6BBJ), which appears to be in a different impermeable state—we hypothesize this is the inactivated state.
The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis

The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 μM or 1.6 μM half maximal effective concentration (EC50) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity.
The Antioxidant from Ethanolic Extract of Rosa cymosa Fruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect

Rosa cymosa Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of R. cymosa fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of R. cymosa fruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150 μg/mL) triggered apoptosis by 26.52–83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44–58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets of R. cymosa against hematologic cancer cells suggested its potential application as an antileukemic dietary supplement.
Comparison of Diatoms and Dinoflagellates from Different Habitats as Sources of PUFAs

Recent studies have clearly shown the importance of omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) for human and animal health. The long-chain eicosapentaenoic acid (EPA; 20:5ω-3) and docosahexaenoic acid (DHA; 22:6ω-3) are especially recognized for their nutritional value, and ability to alleviate many diseases in humans. So far, fish oil has been the main human source of EPA and DHA, but alternative sources are needed to satisfy the growing need for them. Therefore, we compared a fatty acid profile and content of 10 diatoms and seven dinoflagellates originating from marine, brackish and freshwater habitats. These two phytoplankton groups were chosen since they are excellent producers of EPA and DHA in aquatic food webs. Multivariate analysis revealed that, whereas the phytoplankton group (46%) explained most of the differences in the fatty acid profiles, habitat (31%) together with phytoplankton group (24%) explained differences in the fatty acid contents. In both diatoms and dinoflagellates, the total fatty acid concentrations and the ω-3 and ω-6 PUFAs were markedly higher in freshwater than in brackish or marine strains. Our results show that, even though the fatty acid profiles are genetically ordered, the fatty acid contents may vary greatly by habitat and affect the ω-3 and ω-6 availability in food webs.
Beer Molecules and Its Sensory and Biological Properties: A Review

The production and consumption of beer plays a significant role in the social, political, and economic activities of many societies. During brewing fermentation step, many volatile and phenolic compounds are produced. They bring several organoleptic characteristics to beer and also provide an identity for regional producers. In this review, the beer compounds synthesis, and their role in the chemical and sensory properties of craft beers, and potential health benefits are described. This review also describes the importance of fermentation for the brewing process, since alcohol and many volatile esters are produced and metabolized in this step, thus requiring strict control. Phenolic compounds are also present in beer and are important for human health since it was proved that many of them have antitumor and antioxidant activities, which provides valuable data for moderate dietary beer inclusion studies.
Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines

The need for improved dengue vaccines remains since the only licensed vaccine, Dengvaxia, shows variable efficacy depending on the infecting dengue virus (DENV) type, and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination. Here, we developed a tetravalent dengue purified and inactivated vaccine (DPIV) candidate and characterized, in rhesus macaques, its immunogenicity and efficacy to control DENV infection by analyzing, after challenge, both viral replication and changes in biological markers associated with dengue in humans. Although DPIV elicited cross-type and long-lasting DENV-neutralizing antibody responses, it failed to control DENV infection. Increased levels of viremia/RNAemia (correlating with serum capacity at enhancing DENV infection in vitro), AST, IL-10, IL-18 and IFN-γ, and decreased levels of IL-12 were detected in some vaccinated compared to non-vaccinated monkeys, indicating the vaccination may have triggered antibody-dependent enhancement of DENV infection. The dengue macaque model has been considered imperfect due to the lack of DENV-associated clinical signs. However, here we show that post-vaccination enhanced DENV infection can be detected in this model when integrating several parameters, including characterization of DENV-enhancing antibodies, viremia/RNAemia, and biomarkers relevant to dengue in humans. This improved dengue macaque model may be crucial for early assessment of efficacy and safety of future dengue vaccines.
Development of an evidence-based e-health readiness assessment framework for Uganda

Background: While e-health readiness assessment is vital to the successful implementation of e-health innovations, there is little published guidance (i.e. e-health readiness assessment frameworks (eHRAFs)) for institutions and countries. Objective: To develop an evidence-based and locally relevant eHRAF for Uganda. Method: A list of possible e-health readiness domains and constructs was developed through a structured review of the e-health literature. This list was first refined using author experience, insight and reflection. Based on this refined list, an eHRAF questionnaire was developed, which was initially pilot tested for face and content validity. Thereafter, it was distributed to 13 purposively selected study participants who were Ugandan e-health experts from the fields of health, information and communications technology (ICT) and academia. The questionnaire was discussed in a focus group setting for consensus input, where study participants confirmed, rejected or revised proposed domains and constructs suitable to guide e-health readiness assessment at either the national or site-specific level within Uganda. Results: Of 148 identified literature resources, 13 met inclusion criteria. A subjective review highlighted 11 frequently used e-health domains. Further reflection reduced these to nine domains, which were shared with study participants by means of the questionnaire. Based upon prior use of, and familiarity with, a management tool (PESTEL), participants’ consensus on factors essential for readiness assessment in Uganda was aligned with PESTEL’s six domains: political, economic, sociocultural, technological, environmental, and legal and regulatory. The participants considered engagement, and core and societal readiness as optional domains. Based on this input, the authors developed a proposed eHRAF suitable for Uganda, comprised of domains, sub-domains and constructs. Conclusion: The eHRAF developed in this research is an evidence-based framework (literature and cross-sectoral expert opinion) and consists of primary domains, sub-domains and constructs suitable for assessing e-health readiness in Uganda, either nationally or locally, prior to implementation of any e-health system. The process and principles may have utility in other countries. Implications: A national, culturally relevant, context-specific Ugandan eHRAF could facilitate efficient and effective planning and implementation of new e-health programmes across the country and assist policymakers and legislators to develop consistent and reliable guidelines and regulations.
Text Messaging Interventions for Reducing Alcohol Consumption Among Harmful and Hazardous Drinkers: Protocol for a Systematic Review and Meta-Analysis

Background Mobile phone-based interventions have become popular for lifestyle behavior change, particularly the use of text messaging as it is a technology ubiquitous in mobile phones. Reviews and meta-analyses of digital interventions for reducing harmful and hazardous use of alcohol have mainly focused on Web-based interventions; thus, there is a need for a body of evidence to guide health practitioners, policy makers, and researchers with respect to the efficacy of available text messaging interventions. Objective The aim of this systematic review and meta-analysis is to assess the effectiveness of text messaging interventions for reducing the amount of alcohol consumed among harmful and hazardous drinkers; this is compared to receiving no, minimal, or unrelated health information. Specifically, we ask the following questions: (1) Can interventions consisting of only text messages be effective in reducing alcohol consumption compared to no intervention or a minimal or unrelated intervention? (2) Can interventions consisting of only text messages be effective in reducing the prevalence of risky drinking compared to no intervention or a minimal or unrelated intervention? Methods Several databases will be searched, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, the Conference Proceedings Citation Index, ClinicalTrials.gov, OpenGrey, among others. Reports of studies that evaluate text messaging interventions for reducing the amount of alcohol consumed will be included. Primary outcomes of interest will be weekly alcohol consumption and frequency of heavy episodic drinking. The Cochrane Collaboration Risk of Bias tool will be used to assess bias in reports, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach will be used to assess the quality of the body of evidence. A narrative review will be presented, and a meta-analysis will be conducted in case of homogeneity among included studies. Results The systematic review has not yet begun but is expected to start in May of 2019; publication of the final review and meta-analysis is expected at the end of 2019. Conclusions The technology for text messaging is ubiquitous in mobile phones; thus, the potential reach of interventions utilizing this technique is great. However, there are no meta-analyses to date that limit the scope to the use of text messaging interventions for alcohol consumption reduction. Therefore, the proposed systematic review and meta-analysis will help health practitioners, policy decision makers, researchers, and others to better understand the effects of these interventions. International Registered Report Identifier (IRRID) PRR1-10.2196/12898
Effect of ginger (Zingiber officinale) on semen quality

To date, according to the Scopus database, the biological effects of ginger (binominal name: Zingiber officinale), or ginger extracts, and its derived compounds on semen quality and sperm parameters have been revealed in more than 35 original articles. Though, still, there are no collective systematic or narrative discussion and conclusion of this specific research streak. Here, we systematically review and summarise the current link between ginger and its bioactive compounds with semen quality. To achieve this, we searched the central databases (Scopus and PubMed) for original studies, published in English language from August 2004 through February 2019 using the keywords “ginger” versus “sperm” and “semen. ” In summary, there is solid evidence that ginger enhances semen quality and improves the main sperm parameters such as concentration, viability, motility and morphology. Such beneficial effects of ginger on semen quality are attributable, at least in part, to increased levels of gonadal hormones, in particular, testosterone and luteinising hormone, decreased oxidative damage to cells, increased production of nitric oxide, hypoglycaemic response of ginger and the presence of valued nutrients in ginger such as manganese. Still, the positive effects of ginger on semen quality require additional approval in men.
Opposite alterations of endothelin-1 in lung and pulmonary artery mirror gene expression of bone morphogenetic protein receptor 2 in experimental pulmonary hypertension

Abstract Aim of the Study: Endothelin-1 (ET-1) overexpression was suggested to play a role in pulmonary hypertension (PH). However, the roles of ET-1 in early stages of PH remain unexplored. We examined the expression of ET-1 and relevant disease progression markers in the pulmonary artery and the lungs during the development of PH induced by monocrotaline (MCT). Material and Methods: Male 12-weeks-old Wistar rats were administered with MCT (60 mg/kg, s.c.) or saline (CON). We measured right ventricular pressure (RVP) by catheterization under tribromoethanol anesthesia; hemoglobin oxygen saturation, breathing rate were measured by pulse oximetry in conscious animals. Rats were sacrificed 1, 2 or 4 weeks after MCT. mRNA levels of ET-1, its receptors, inflammatory markers IL-1beta, TNFalpha, IL-6 and genes related to VSMC proliferation or lung damage (Bmpr2, nestin, Pim1, PAI-1, TGFbeta-1) were analyzed by RT-qPCR. Results: RVP and breathing rate increased and hemoglobin oxygen saturation decreased after MCT only at week 4. Lung weight was increased at all time points. ET-1 was upregulated in the pulmonary artery at weeks 1 and 4, while being clearly suppressed in the lungs at all times. Bone morphogenetic protein receptor 2 followed a similar pattern to ET-1. PAI-1 markedly increased in the MCT lungs (but not pulmonary artery) from week 1 to 4. Nestin peaked at week 2 in both tissues. TGFbeta-1 increased in both tissues at week 4. ET-1 expression did not correlate with other genes, however, Bmpr2 tightly negatively correlated with PAI-1 in the lungs, but not pulmonary artery of MCT groups. Conclusions: ET-1 overexpression in the pulmonary artery preceded development of PH, but it was clearly and unexpectedly downregulated in the lungs of monocrotaline-treated rats and showed no correlation to disease progression markers. We speculate that endothelin-1 may play opposing roles in the lungs vs pulmonary artery in monocrotaline-induced PH.