Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans

Background The current strategy for the elimination of onchocerciasis is based on annual or bi-annual mass drug administration with ivermectin. However, due to several limiting factors there is a growing concern that elimination of onchocerciasis cannot be achieved solely through the current strategy. Additional tools are critically needed including a prophylactic vaccine. Presently Ov-103 and Ov-RAL-2 are the most promising vaccine candidates against an Onchocerca volvulus infection. Methodology/Principal findings Protection induced by immunization of mice with the alum-adjuvanted Ov-103 or Ov-RAL-2 vaccines appeared to be antibody dependent since AID-/- mice that could not mount antigen-specific IgG antibody responses were not protected from an Onchocerca volvulus challenge. To determine a possible association between antigen-specific antibody responses and anti-larvae protective immunity in humans, we analyzed the presence of anti-Ov-103 and anti-Ov-RAL-2 cytophilic antibody responses (IgG1 and IgG3) in individuals classified as putatively immune, and in infected individuals who developed concomitant immunity with age. It was determined that 86% of putatively immune individuals and 95% individuals with concomitant immunity had elevated IgG1 and IgG3 responses to Ov-103 and Ov-RAL-2. Based on the elevated chemokine levels associated with protection in the Ov-103 or Ov-RAL-2 immunized mice, the profile of these chemokines was also analyzed in putatively immune and infected individuals; both groups contained significantly higher levels of KC, IP-10, MCP-1 and MIP-1β in comparison to normal human sera. Moreover, human monospecific anti-Ov-103 antibodies but not anti-Ov-RAL-2 significantly inhibited the molting of third-stage larvae (L3) in vitro by 46% in the presence of naïve human neutrophils, while both anti-Ov-103 and anti-Ov-RAL-2 antibodies significantly inhibited the molting by 70–80% when cultured in the presence of naive human monocytes. Interestingly, inhibition of molting by Ov-103 antibodies and monocytes was only in part dependent on contact with the cells, while inhibition of molting with Ov-RAL-2 antibodies was completely dependent on contact with the monocytes. In comparison, significant levels of parasite killing in Ov-103 and Ov-RAL-2 vaccinated mice only occurred when cells enter the parasite microenvironment. Taken together, antibodies to Ov-103 and Ov-RAL-2 and cells are required for protection in mice as well as for the development of immunity in humans. Conclusions/Significance Alum-adjuvanted Ov-103 and Ov-RAL-2 vaccines have the potential of reducing infection and thus morbidity associated with onchocerciasis in humans. The development of cytophilic antibodies, that function in antibody-dependent cellular cytotoxicity, is essential for a successful prophylactic vaccine against this infection.
Measuring lower limb circumference and volume – introduction of a novel optical 3D volumetric measurement system

Abstract This study comprised two experiments: (1) the reliability of a novel optical three-dimensional (3D) volumetric measurement system (BODYTRONIC® 600) for the assessment of lower limb circumference and volume; (2) the comparison of data obtained from BODYTRONIC® 600 with that provided by computed tomography (CT) for accuracy estimation. Reliability was assessed in 20 healthy subjects. Accuracy was determined by comparing the deviations in the surface topology of two 3D models obtained from BODYTRONIC® 600 and CT. Reliability was very high for leg circumference measures [coefficient of variations (CVs) range 0.3%–1.3%] and slightly lower for foot circumference (CVs around 2.0%). Reliability of leg volume was also found to be very high (CVs ≤ 2.5%). Differences in surface topology between BODYTRONIC® 600 and CT were primarily below 1 mm indicating high accuracy. The volumes of the foot were higher (range 0.9%–1.7%) and that of the leg, lower (range 1.0%–1.3%) compared to CT. The BODYTRONIC® 600 system provides fast, highly reliable and accurate measures of lower limb circumference and volume and can be considered as a valuable measurement tool for use in various research and clinical applications.
Hospital-Based Quality Improvement Interventions for Patients With Acute Coronary Syndrome: A Systematic Review.

BACKGROUND Quality improvement initiatives have been developed to improve acute coronary syndrome care largely in high-income country settings. We sought to synthesize the effect size and quality of evidence from randomized controlled trials (RCTs) and nonrandomized studies for hospital-based acute coronary syndrome quality improvement interventions on clinical outcomes and process of care measures for their potential implementation in low- and middle-income country settings. METHODS AND RESULTS We conducted a bibliometric search of databases and trial registers and a hand search in 2016 and performed an updated search in May 2018 and May 2019. We performed data extraction, risk of bias assessment, and quality of evidence assessments in duplicate. We assessed differences in outcomes by study design comparing RCTs to nonrandomized quasi-experimental studies and by country income status. A meta-analysis was not feasible due to substantial, unexplained heterogeneity among the included studies, and thus, we present a qualitative synthesis. We screened 5858 records and included 32 studies (14 RCTs [n=109 763] and 18 nonrandomized quasi-experimental studies [n=54-423]). In-hospital mortality ranged from 2.1% to 4.8% in the intervention groups versus 3.3% to 5.1% in the control groups in 5 RCTs (n=55 942). Five RCTs (n=64 313) reported 3.0% to 31.0% higher rates of reperfusion for patients with ST-segment-elevation myocardial infarction in the intervention groups. The effect sizes for in-hospital and discharge medical therapies in a majority of RCTs were 3.0% to 10.0% higher in the intervention groups. There was no significant difference in 30-day mortality evaluated by 4 RCTs (n=42 384), which reported 2.5% to 15.0% versus 5.9% to 22% 30-day mortality rates in the intervention versus control groups. In contrast, nonrandomized quasi-experimental studies reported larger effect sizes compared to RCTs. There were no significant consistent differences in outcomes between high-income and middle-income countries. Low-income countries were not represented in any of the included studies. CONCLUSIONS Hospital-based acute coronary syndrome quality improvement interventions have a modest effect on process of care measures but not on clinical outcomes with expected differences by study design. Although quality improvement programs have an ongoing and important role for acute coronary syndrome quality of care in high-income country settings, further research will help to identify key components for contextualizing and implementing such interventions to new settings to achieve their desired effects. Systematic Review Registration: URL: https://www.crd. york.ac. uk/PROSPERO/. Unique identifier: CRD42016047604.
The “Who Do You Tell?”™ Child Sexual Abuse Education Program: Eight Years of Monitoring

ABSTRACT School-based programs have been the central strategy to educate children about the serious nature of child sexual abuse (CSA) in the hope of prevention or early intervention. While program evaluations consistently show significant improvement in children’s knowledge and skills, it behooves programs to monitor their impacts. Monitoring, or on-going assessments, can take several forms but in the current study refers to monitoring the outcome of knowledge of CSA prevention concepts. The “Who Do You Tell? ”™ child sexual abuse education program has been offered for 35 years in Calgary, Canada and was previously evaluated in a randomized pre-test-post-test comparison study with strong positive findings. This article presents the results of subsequently monitoring program outcomes over an eight-year period (2010–2017), examining knowledge/attitudes in 6198 students in 50 schools in a Western Canadian city. All students significantly increased their CSA knowledge/attitudes with large effect sizes. Practice and policy implications are discussed.
Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation

Glucocorticoids contribute to the increased incidence of secondary osteoporosis. Hydrogen sulfide (H2S) is a gasotransmitter and plays an essential role in bone metabolism. In this study, we investigated the therapeutic effects of H2S on glucocorticoid-induced osteoporosis (GIO). We found that dexamethasone (Dex) decreased serum H2S and two key H2S-generating enzymes in the bone marrow in vivo, cystathione b-synthase and cystathione g-lyase. Treatment of H2S-donor GYY4137 in rat significantly relieved the inhibitory effect of Dex on bone formation. Dex inhibited osteoblasts proliferation and osteogenic differentiation and decreased the expressions of the two H2S-generating enzymes. Further investigation showed that H2S was involved in Dex-mediated osteoblasts proliferation, differentiation, and apoptosis. Mechanistically, GYY4137 promoted osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands. In comparison, the blockage of Wnt/β-catenin signaling pathway significantly alleviated the effect of H2S on osteoblasts. In conclusion, the restoration of H2S levels is a potential novel therapeutic approach for GIO.
RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection

Hepatitis C virus (HCV) is a positive-strand RNA virus replicating in a membranous replication organelle composed primarily of double-membrane vesicles (DMVs) having morphological resemblance to autophagosomes. To define the mechanism of DMV formation and the possible link to autophagy, we conducted a yeast two-hybrid screening revealing 32 cellular proteins potentially interacting with HCV proteins. Among these was the Receptor for Activated Protein C Kinase 1 (RACK1), a scaffolding protein involved in many cellular processes, including autophagy. Depletion of RACK1 strongly inhibits HCV RNA replication without affecting HCV internal ribosome entry site (IRES) activity. RACK1 is required for the rewiring of subcellular membranous structures and for the induction of autophagy. RACK1 binds to HCV nonstructural protein 5A (NS5A), which induces DMV formation. NS5A interacts with ATG14L in a RACK1 dependent manner, and with the ATG14L-Beclin1-Vps34-Vps15 complex that is required for autophagosome formation. Both RACK1 and ATG14L are required for HCV DMV formation and viral RNA replication. These results indicate that NS5A participates in the formation of the HCV replication organelle through interactions with RACK1 and ATG14L.
Relations Among Corneal Curvature, Thickness, and Volume in Keratoconus as Evaluated by Anterior Segment-Optical Coherence Tomography.

Purpose To provide insight into the mechanism underlying corneal deformation in keratoconus, we examined the relations among corneal curvature, thickness, and volume as well as the association of corneal scar formation with these parameters. Methods A total of 288 corneas of 174 keratoconus patients and 114 corneas of 57 control subjects were examined by anterior segment-optical coherence tomography (AS-OCT). Anterior and posterior refractive values, corneal thickness (CT), and corneal volume (CV) were determined by AS-OCT for both control and keratoconic eyes. The pattern of corneal stromal scarring was also determined from the AS-OCT images. Results The distribution of CV was similar for keratoconic and control eyes, whereas anterior and posterior refractive values as well as CT showed a wider distribution for keratoconic eyes. The progression of corneal deformation initially occurred without corneal thinning but was later associated with a decrease in CT and an eventual loss of CV. The progression of scarring from the anterior to the posterior stroma was associated with an increase in anterior refractive value and decreases in posterior refractive value, CT, and CV. Conclusions The progression of keratoconus as reflected by corneal deformation was associated with a reduction in CT and CV as well as stromal scar formation. The loss of CV occurred after the initial decline in CT, suggesting that stromal degradation occurred only at the advanced stage of keratoconus.
Knockout model reveals the role of Nischarin in mammary gland development, breast tumorigenesis and response to metformin treatment

Previously, our lab discovered the protein Nischarin and uncovered its role in regulating cell migration and invasion via its interactions with several proteins. We subsequently described a role for Nischarin in breast cancer, in which it is frequently underexpressed. To characterize Nischarin's role in breast tumorigenesis and mammary gland development more completely, we deleted a critical region of the Nisch gene (exons 7–10) from the mouse genome and observed the effects. Mammary glands in mutant animals showed delayed terminal end bud formation but did not develop breast tumors spontaneously. Therefore, we interbred the animals with transgenic mice expressing the mouse mammary tumor virus‐polyoma middle T‐antigen (MMTV‐PyMT) oncogene. The MMTV‐PyMT mammary glands lacking Nischarin showed increased hyperplasia compared to wild‐type animal tissues. Furthermore, we observed significantly increased tumor growth and metastasis in Nischarin mutant animals. Surprisingly, Nischarin deletion decreased activity of AMPK and subsequently its downstream effectors. Given this finding, we treated these animals with metformin, which enhances AMPK activity. Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin‐deficient breast cancers.
Child Sexual Abuse and Situational Context: Children’s Experiences in Post-Conflict Northern Uganda

ABSTRACT Although substantial literature exists on child sexual abuse (CSA), little is known about abuses children encounter in northern Uganda, a post-conflict area. Media reports have indicated a high incidence for CSA. The study, firstly, explored boys’ and girls’ experiences of sexual abuse by adults in this post-conflict region and secondly, interventions directed at improving the current situation of children at risk of child abuse and the survivors were investigated as well. The study was guided by radical feminism and nested ecological framework theories. Semi-structured interviews were conducted involving 43 sexually abused children. Narrative responses were audio recorded and transcribed. Content qualitative analysis was used to understand sexual offenses from children’s perspectives. Participants mentioned the following as the most perilous situations; laxity in parental roles, cultural norms, and practices, patriarchal attitudes, child sexual desires and attitudes, family breakdown and alcoholism. The study found many reported cases of CSA in the region. The results imply the exigent need of separate units specifically for reporting and handling child sexual offenses, need for personnel training on gender issues and filing system in child protection agencies and family programs for both fathers and mothers on child protection strategies for prevention and mitigation of CSA.
NLRX1 inhibits the early stages of CNS inflammation and prevents the onset of spontaneous autoimmunity

Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1−/− mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity.
Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management

Systemic corticosteroid use to manage uncontrolled asthma and its associated healthcare burden may account for important health-related adverse effects. We conducted a systematic literature review to investigate the real-world extent and burden of systemic corticosteroid use in asthma. We searched MEDLINE and Embase databases to identify English-language articles published in 2010–2017, using search terms for asthma with keywords for oral corticosteroids and systemic corticosteroids. Observational studies, prescription database analyses, economic analyses, and surveys on oral/systemic corticosteroid use in children (>5 yr old), adolescents (12–17 yr old), and adults with asthma were included. We identified and reviewed 387 full-text articles, and our review included data from 139 studies. The included studies were conducted in Europe, North America, and Asia. Overall, oral/systemic corticosteroids were commonly used for asthma management and were more frequently used in patients with severe asthma than in those with milder disease. Long-term oral/systemic corticosteroid use was, in general, less frequent than short-term use. Compared with no use, long-term and repeated short-term oral/systemic corticosteroid use were associated with an increased risk of acute and chronic adverse events, even when doses were comparatively low. Greater oral/systemic corticosteroid exposure was also associated with increased costs and healthcare resource use. This review provides a comprehensive overview of oral/systemic corticosteroid use and associated adverse events for patients with all degrees of asthma severity and exposure duration. We report that oral/systemic corticosteroid use is prevalent in asthma management, and the risks of acute and chronic complications increase with the cumulative oral corticosteroid dosage.
The development of FTIR-imaging for the study of human prostate cancer biopsies

The University of ManchesterKonrad Matthew DorlingDoctor of Philosophy? The Development of FTIR-Imaging for the Study of Human Prostate Cancer Biopsies? 2012The potential of using FTIR imaging as analytical technique combined with pre-processing and multivariate analysis methods was investigated. FTIR spectroscopy has been used in the past to investigate aspects of prostate cancer cells and tissues, successfully showing the separation of spectral data taken from benign prostate samples and cancerous prostate samples of varying Gleason grade. This work was ground-breaking, diagnosing different grades of cancer in the same way to the original histopathologist-assigned grades of the tissue. The advent of FTIR imaging and its recent commercial availability has allowed the much more specific collection of FTIR spectra in the form of infrared images corresponding to hyperspectral cubes of data. Optimised protocols for FTIR imaging were developed for the collection of such images from prostate cancer tissue samples, so that the highest quality data could be obtained as time efficiently as possible. With the recent development of a resonant Mie scattering correction algorithm, the pre-processing of data could be done rigorously, eliminating all physical effects from spectral data for the first time. Hierarchical cluster analysis and K-means cluster analysis were employed as image clustering methods to classify the tissue based on morphology. Imaging data that had RMieS-EMSC, vector normalisation and a second derivative applied showed the best cluster assignment as advised by an experienced histopathologist.A large scale study was devised based on the author? s previous work to try and classify metastatic from non-metastatic prostate cancer epithelium using FTIR images. A method for the isolation of epithelial spectra was devised by the immunohistochemical staining of the tissue sample after data collection to highlight the epithelium, and overlaying the optical image of the stained tissue with the FTIR image. Resulting epithelial spectra were extracted from the FTIR images of the two tissue classes. Principal component analysis was applied to the data, and artificial neural network were constructed using training and test sets of patient-associated spectra. Experiments were done investigating whether non-metastatic cancer epithelium classified differently to non-cancerous epithelium, and whether epithelial spectra from patients with metastatic cancer would classify differently to patients with non-metastatic cancer. The non-metastatic data did not separate well from the non-cancer data. PCA results showed the metastatic data separated from the non-metastatic data very well, and seemingly robust ANNs were also developed to classify the data.
Needle-stick stuffs with safety device for prevention of percutaneous injuries: a literature review

Objective: to identify the literature on the use of needle-stick stuffs with safety devices for prevention of accidents. Method: descriptive study, of the type of integrative review of literature, with a survey of articles from the following databases: MEDLINE / PubMed, LILACS, Science Direct, SCOPUS, and Cochrane, from the research question << Do the needle-stick stuffs with safety devices reduce percutaneous injuries among the health professionals? >> For the sample, we elected 15 articles, presented in a figure. Results: the analysis of the eligible articles in this review showed a significant reduction in percutaneous injuries, ranging from 0.8% to 93% among healthcare professionals, with the use of objects with safety devices within their workplaces. Conclusion: needle-stick stuffs with safety devices reduce percutaneous injuries in the healthcare services; however, we should highlight the importance of active participation of high management, administration, coordination, and healthcare professionals from hospital institutions. Descriptors: Protective Equipment; Penetrating Injuries; Health Professional.