Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional crosstalk between helper bacteriophages and Staphylococcus aureus pathogenicity islands

TRANSCRIPTIONAL CROSSTALK BETWEEN HELPER BACTERIOPHAGES AND STAPHYLOCOCCUS AUREUS PATHOGENICITY ISLANDS By Kristin Downie Lane A dissertation submitted in partial fulfillment of the requirement for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2013 Major Director: Gail E. Christie, Ph.D. Professor, Department of Microbiology and Immunology Acquisition of a superantigen pathogenicity island (SaPI) significantly increases virulence in Staphylococcus aureus. Horizontal transfer of SaPIs occurs at high frequency and depends upon a helper bacteriophage, either through direct infection or SOS-mediated induction of a lysogen. SaPIs hijack the packaging machinery of the helper phage, leading to the formation of SaPI-containing transducing particles that can introduce the pathogenicity island into neighboring SaPI-negative cells. All SaPIs contain a conserved core of genes, some of which are co-transcribed as an operon and encode functions involved in helper
Geotechnics on the move: guidance for a risk-driven way of working

This paper presents a summary of a guide for practitioners about the implementation of geotechnical risk management in organisations in the construction industry. Currently, the guide is only available in Dutch. This paper aims to share the key elements of the book with an international readership. First, the perhaps unusual content and style of the guide and its summary are explained, which is the result of organisational rather than technical research. Then, the reality of geotechnical engineering and construction and an ambitious vision of their future perspective are sketched. In this vision, geotechnical risk management plays a dominant role. However, while straightforward in theory, applying complete geotechnical risk management as a routine proves to be a tough exercise in client, contractor, engineering and project organisations. For this reason, a selection of scientifically derived and practically tested organisational key conditions is presented. These conditions aim to facilitate successfully implementing geotechnical risk management in (project) organisations. Finally, this paper gives 10 lessons that have been learned from practice. The lessons aim to support engineers, managers and executives, while they are routinely applying geotechnical risk management in their organisations. This should increase the success rate of projects at a reasonable cost.
Expression of the Xhox3 Homeobox Protein in Xenopus Embryos: Blocking Its Early Function Suggests the Requirement of Xhox3 for Normal Posterior Development

Antibodies directed against the product of the Xenopus homeobox gene Xhox3 were raised and used to localize the expression of Xhox3 in the embryo at different stages of development. These studies suggest that endogenous Xhox3 protein is distributed in a graded fashion in the nuclei of mesodermal cells along the anterior‐posterior (A‐P) and dorso‐ventral (D‐V) axes in the postgastrula embryo with low levels in anterior and ventral regions and higher levels in posterior and dorsal regions. Xhox3 protein is also detected at different times in the midbrain, spinal cord and hindbrain. In the hindbrain, Xhox3 displays different metameric expression patterns in dorsal and ventral regions during early embryogenesis and metamorphosis. We have tested for the early function of Xhox3 by injecting antibodies against the Xhox3 protein into the cytoplasm of developing embryos. A significant number of embryos injected with Xhox3 antibodies show posterior (trunk and tail) deficiencies. This posterior deficient phenotype constitutes the opposite of the anterior (head) deficient phenotype obtained after overexpresson of Xhox3 reported previously. These results suggest that expression of Xhox3 in the posterior mesoderm is necessary for posterior development and that the graded distribution of Xhox3 in the embryonic mesoderm is required for the development of normal embryonic axial pattern.
Supplemental Data Global Regulators Orchestrate Group II Intron Retromobility

Plasmid copy number (PCN) was determined after induction of the donor intron. Total genomic and plasmid DNA was isolated using the QIAGEN QIAamp DNA kit according to the manufacturer’s protocol. Standard quantitative PCR conditions, using SYBER green master mix (Applied Biosystems), were then used as described in Supplementary Table S2 by (Coros et al., 2008). A standard curve of fluorescence versus cycle number (C
Book Review

Originating as a set of conference papers in 2007, this ten-chapter volume edited by Tan Chee-Beng aims to describe the historical contribution of Chinese cuisine to current Southeast Asian foodways both within the region and as practiced among diverse emigrant populations. As reflected in the generality of the title, this collection adopts a broad scope, making selec­ tive coverage a necessity. It centers on a series of individually-authored, Southeast Asian case studies drawn from Indonesia, the Philippines, Burma (specifically Mandalay), and Vietnam. These contributions are bookended by an ostensible overview of Chinese food in diaspora and an extension— the promised “and beyond”—which chronicles how Southeast Asian Chinese food is itself exported and reinterpreted in novel, global contexts. The pref­ ace and the editor’s self-authored, initial chapter suggest that this is an essentially descriptive project that aims to align itself with Tan’s (2001) model for the cultural transformation of foodways, in an “attempt to examine the diversity and contribution of the Chinese culinary heritage in Southeast Asia as a result of migration from China and localization in Southeast Asia” (3). Though largely successful in its descriptive mission, many of the case studies bypass Tan’s tripartite cultural transformation model and fail to meaningfully engage with alternative theoretical frameworks, while several introductory and concluding chapters fall outside of the work’s broadly defined scope. The volume is organized in three parts: (1) a three-chapter “overview” of Chinese food in diaspora, (2) a four-chapter case-study series focusing on Chinese influence and culinary variation within Southeast Asia, and (3) a three-chapter extension assessing the adaptation and adoption of variants of Southeast Asian Chinese food in Las Vegas, Australia, and Hong Kong, respectively. The theme and organizational intent is most diffuse in the ini­ tial overview section, which struggles to provide a broader context for the globalization of Chinese food. As volume editor and author of the cultural transformation of foodways model, Tan uses his initial chapter to briefly revisit this framework and apply it to examples of Chinese Malayan food. Focusing on migrant populations rather than products, Tan proposes that culinary practice in diaspora is
Evidence of rotavirus vaccine impact in sub-Saharan Africa: Systematic review and meta-analysis

Background Over 34 countries in Africa have introduced rotavirus vaccine to their national immunization programs: monovalent (Rotarix®, RV1) and pentavalent (RotaTeq®, RV5) after South Africa introduced it in 2009. Since then several studies assessing the impact of the vaccine have been conducted. The principal aim of this study was to evaluate the impact of rotavirus vaccine in sub-Saharan Africa. Methods A Literature search was performed using Mendeley, PubMed, ScienceDirect, grey literature and Web of Science databases of published studies from January 1, 2017, as years of recent publications on rotavirus vaccine impact in sub-Saharan Africa. A meta-analysis was conducted for rotavirus infection in children under 5 years using proportions of pre and post-vaccine introduction in these populations. Random-effect estimates were considered since the samples were from universal populations. Results Out of the 935 articles identified, 17 studies met the inclusion for systematic review and meta-analysis. The pooled proportion for pre-vaccination period was 42%, 95% (CI: 38–46%), and reduced to 21%, 95% (CI: 17–25%) during post-vaccination period. Rotavirus diarrhea significantly reduced in children < 12 months as compared to children 12–24 months old. Seasonal peaks of rotavirus diarrhea were between June–September. However, data is limited to one year of post-vaccine introduction, and bias may present due to early vaccine impact. Conclusion We observed that the introduction of the rotavirus vaccine was partly responsible for the significant reduction in the burden of rotavirus-associated diarrhea in sub-Saharan Africa. Therefore, there is a need to encourage the remaining countries to introduce the vaccine to their routine national immunization programs.
Drug Research Meets Network Science: Where Are We?

Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some examples of how the networks can be used to investigate drug-related systems. A section is devoted to network-based inference applications, i.e., prediction methods based on interactomes, that can be used to identify putative drug–target interactions without resorting to 3D modeling. Finally, we present some aspects of Boolean networks dynamics, anticipating that it might become a very potent modeling framework to develop in silico screening protocols able to simulate phenotypic screening experiments. We conclude that network applications integrated with machine learning and 3D modeling methods will become an indispensable tool for computational drug discovery in the next years.
The Risk of Venous Thromboembolism in Patients with Gallstones

The objective of this study is to assess the relationship between gallstones and venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and the risk of VTE after cholecystectomy for gallstones. This nationwide population-based cohort study retrieved the hospitalization database from the Longitudinal Health Insurance Research Database (LHID2000), a database belonging to the National Health Insurance (NHI) program of Taiwan. A total of 345,793 patients aged ≥ 18 years with gallstones diagnosed between 2000 and 2010 were identified as the study cohort. The beneficiaries without gallstones were randomly selected as the control cohort by propensity score matching with the study cohort at a 1:1 ratio based on age, sex, urbanization, occupation, comorbidities, and year of the index date. We compared the risk of VTE between both cohorts and measured the risk differences of VTE between the gallstones patients with (n = 194,187) and without cholecystectomy (n = 151,606). Each patient was examined from the index date until the occurrence of DVT or PE, death or withdrawal from the NHI program, or the end of 2011. The incidence rate of DVT was 7.94/10,000 person-years for the non-gallstones cohort and 9.64/10,000 person-years for the gallstones cohort (hazard ratio (HR) = 1.35, 95% confidence interval (CI) = 1.25–1.47), respectively (p < 0.001). The incidence rate of PE was 3.92/10,000 person-years for the non-gallstones cohort and 4.65/10,000 person-years for the gallstones cohort (HR = 1.35, 95% CI = 1.20–1.53), respectively (p < 0.001). The cumulative incidence of DVT (6.54/10,000 person-years vs 14.6/10,000 person-years, adjusted hazard ratio (aHR) = 0.60, 95% CI = 0.54–0.67) and PE (3.29/10,000 person-years vs 6.84/10,000 person-years, aHR = 0.67, 95% CI = 0.58–0.77) for gallstones patients was lower in the cholecystectomy cohort than that in the non-cholecystectomy cohort after adjustment for age, sex, urbanization level, occupation, frequency of medical visits, history of pregnancy, and comorbidities (log-rank test, p < 0.001). Our findings indicate that the risk of DVT or PE in patients with gallstones was greater than those without gallstones. However, the risk of DVT and PE in the patients with gallstones would decrease after cholecystectomy. This area of research needs more studies to ascertain the pathogenesis for the contribution of gallstones to the development of VTE and the protective mechanisms of cholecystectomy against the development of VTE.
Quantitative imaging of coronary flows using 3D ultrafast Doppler coronary angiography

Coronary flow rate remains complex to assess in clinical practice using non-invasive, non-ionizing imaging tools. In this study, we introduce 3D ultrafast Doppler coronary angiography (3D UDCA), an ultrasound-based method to assess coronary blood flows in three-dimensions at high volume-rate and in one single heartbeat. We demonstrate that 3D UDCA can visualize the coronary vasculature with high temporal and spatial resolution and quantify the absolute flow. The feasibility of the technique was demonstrated in an open-chest swine model. The flow rate of the left-anterior descending artery (LAD) assessed by 3D UDCA was reconstructed successfully at the early diastolic and late diastolic phases and was in good agreement with an invasive gold-standard flowmeter during baseline, reactive hyperemia and coronary stenosis (r2 = 0.84). Finally, we demonstrate that a coronary stenosis on the LAD can be visualized as well as its associated flow acceleration.
Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-related nausea and vomiting, respectively. An increasing number of preclinical studies have established that ∆9-THC can inhibit the growth and proliferation of cancerous cells through the modulation of cannabinoid receptors (CB1R and CB2R), but clinical confirmation remains lacking. In parallel, the anti-cancer properties of non-THC cannabinoids, such as cannabidiol (CBD), are linked to the modulation of non-CB1R/CB2R G-protein-coupled receptors, neurotransmitter receptors, and ligand-regulated transcription factors, which together modulate oncogenic signalling and redox homeostasis. Additional evidence has also demonstrated the anti-inflammatory properties of cannabinoids, and this may prove relevant in the context of peritumoural oedema and the tumour immune microenvironment. This review aims to document the emerging mechanisms of anti-cancer actions of non-THC cannabinoids.
Minimal clinically important differences in average, best, worst and current intensity and unpleasantness of chronic breathlessness

Background Chronic breathlessness has devastating consequences. The minimal clinically important difference (MCID) for current intensity has been estimated as 9 mm on a 100-mm visual analogue scale (VAS). We aimed to determine MCIDs for commonly used dimensions and recall periods: the current unpleasantness and current, average, best and worst intensity of the past 24 h for chronic breathlessness. Methods This was a secondary analysis of a randomised controlled trial of morphine versus placebo over 7 days in people with chronic breathlessness from severe disease. The breathlessness scores were self-reported using a diary each evening on 100-mm VAS. The MCID for improvement in each score was estimated using anchor-based and distribution-based methods. Results 283 participants (mean age 74.2 years; 63% male; 58% COPD; 87.0% modified Medical Research Council (mMRC) score 3–4) were included. Anchor-based MCIDs for breathlessness scores ranged from −13.9 mm to −9.5 mm. The MCIDs were similar when using different anchors and across all participants, and participants with more severe breathlessness (mMRC 3–4). Distribution-based effect sizes were classed as small (−4.7−6.3 mm), moderate (−9.4−12.5 mm) and large (−15.0−20.0 mm) effect. Sample sizes for trials using the different scores were proposed. MCIDs of absolute change were more stable than using relative change from baseline. Conclusion An improvement of ∼10 mm on a 100-mm VAS is likely to be clinically meaningful across commonly used measures of chronic breathlessness (current intensity, unpleasantness, and average, best and worst intensity over the past 24 h) to evaluate clinical benefit and effects in therapeutic trials. This cohort study determined clinically important differences for current intensity and unpleasantness and the average, best and worst intensity of the past 24 h of chronic breathlessness, which is important for the design of therapeutic trials https://bit.ly/3amslss
An Epilepsy-Associated SV2A Mutation Disrupts Synaptotagmin-1 Expression and Activity-Dependent Trafficking

The epilepsy-linked gene SV2A, has a number of potential roles in the synaptic vesicle (SV) life cycle. However, how loss of SV2A function translates into presynaptic dysfunction and ultimately seizure activity is still undetermined. In this study, we examined whether the first SV2A mutation identified in human disease (R383Q) could provide information regarding which SV2A-dependent events are critical in the translation to epilepsy. We utilized a molecular replacement strategy in which exogenous SV2A was expressed in mouse neuronal cultures of either sex, which had been depleted of endogenous SV2A to mimic the homozygous human condition. We found that the R383Q mutation resulted in a mislocalization of SV2A from SVs to the plasma membrane, but had no effect on its activity-dependent trafficking. This SV2A mutant displayed reduced mobility when stranded on the plasma membrane and reduced binding to its interaction partner synaptotagmin-1 (Syt1). Furthermore, the R383Q mutant failed to rescue reduced expression and dysfunctional activity-dependent trafficking of Syt1 in the absence of endogenous SV2A. This suggests that the inability to control Syt1 expression and trafficking at the presynapse may be key in the transition from loss of SV2A function to seizure activity. SIGNIFICANCE STATEMENT SV2A is a synaptic vesicle (SV) protein, the absence or dysfunction of which is linked to epilepsy. However, the series of molecular events that result in this neurological disorder is still undetermined. We demonstrate here that the first human mutation in SV2A identified in an individual with epilepsy displays reduced binding to synaptotagmin-1 (Syt1), an SV protein essential for synchronous neurotransmitter release. Furthermore, this mutant cannot correct alterations in both Syt1 expression and trafficking when expressed in the absence of endogenous SV2A (to mimic the homozygous human condition). This suggests that the inability to control Syt1 expression and trafficking may be key in the transition from loss of SV2A function to seizure activity.
ANTI-ANGIOGENIC EFFECT OF AQUEOUS EXTRACT OF SHALLOT (ALLIUM ASCALONICUM) BULBS IN RAT AORTA RING MODEL

Objective: Angiogenesis is a key process in the promotion of cancer and its metastasis. Many natural health products inhibit angiogenesis. Because of the lack of molecular studies on anti-tumor and anti-angiogenic effects of shallot (Allium ascalonicum); except a few clinical studies on other shallot properties, such as the anti-proliferative effect of shallot chloroformic extract on two tumor cell lines, the present study focuses on the anti-angiogenic effect of aqueous shallot extract using an aorta ring model. Materials and Methods: Aortic rings were obtained by cross-sectioning, at 1-2 mm intervals, the thoracic aorta of 4-8 weeks old Wistar male rats and cultured them in a thin drop of type I collagen gel. After 3 days of culturing and first sprouting, the extract of A. ascalonicum (from 25 to 800 μg/ml) was added to cultures. The results of anti-angiogenic activity were investigated by microscope. The cytotoxicity of extract at different doses on HUVECs was measured by trypan blue assay. Results: The results showed that the shallot extract has suitable anti-angiogenic effect in a range of 50 to 800 μg/ml, but in 25 μg/ml, the extract has no considerable effect. In addition, a tangible cytotoxic effect on endothelial cells at the above mentioned doses was observed. Conclusion: Our study showed that aqueous extract of A. ascalonicum bulbs has noticeable anti-angiogenic activity without toxic effect on the cells in doses that ranged from 50-800 μg/ ml. Therefore, A. ascalonicum can be a potential candidate for further investigations used in angiogenesis-related pathologic conditions.
Effects of Biannual Azithromycin Mass Drug Administration on Malaria in Malawian Children: A Cluster-Randomized Trial

Abstract. Reductions in malaria morbidity have been reported following azithromycin mass drug administration (MDA) for trachoma. The recent Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin MDA. Here, we investigate the effects of azithromycin MDA on malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and azithromycin or placebo syrup was distributed to children aged 1–59 months for a total of four biannual distributions. At baseline, 12-month, and 24-month follow-up visits, a random sample of 1,200 children was assessed for malaria with thick and thin blood smears and hemoglobin measurement. In the community-level analysis, there was no difference in the prevalence of parasitemia (1.0% lower in azithromycin-treated communities; 95% CI: −8.2 to 6.1), gametocytemia (0.7% lower in azithromycin-treated communities; 95% CI: −2.8 to 1.5), or anemia (1.7% lower in azithromycin-treated communities; 95% CI: −8.1 to 4.6) between placebo and azithromycin communities. Further interrogation of the data at the individual level, both per-protocol (including only those who received treatment 6 months previously) and by intention-to-treat, did not identify differences in parasitemia between treatment arms. In contrast to several previous reports, this study did not show an effect of azithromycin MDA on malaria parasitemia at the community or individual levels.