Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of an Enzyme-Linked Immunosorbent Assay To Detect Antibodies Targeting Recombinant Envelope Protein 2 of Mayaro Virus

Mayaro virus (MAYV) is a neglected arthropod-borne virus (arbovirus) antigenically clustered into the Semliki Forest complex group of Alphavirus genus (Togaviridae family), maintained in an unclear zoonotic cycle involving mosquitoes from Haemagogus genus as the main vector. The genome is composed of a positive single-stranded RNA of 11.5 kb in length, which contains two genes that encode four nonstructural (nsP1 to nsP4) and five structural (C, E3, E2, 6K, and E1) proteins. ABSTRACT Mayaro virus (MAYV) is a neglected arthropod-borne virus (arbovirus) antigenically clustered into the Semliki Forest complex group of Alphavirus genus (Togaviridae family), maintained in an unclear zoonotic cycle involving mosquitoes from Haemagogus genus as the main vector. The genome is composed of a positive single-stranded RNA of 11.5 kb in length, which contains two genes that encode four nonstructural (nsP1 to nsP4) and five structural (C, E3, E2, 6K, and E1) proteins. In the present study, we have developed an enzyme-linked immunosorbent assay (ELISA) using as antigen the recombinant envelope protein 2 of MAYV produced in an Escherichia coli system (rE2-MAYV ELISAs). A panel of 68 human serum samples from suspected arboviral cases was analyzed and titrated for anti-MAYV IgM and IgG antibody detection. The rE2-MAYV ELISA detected 33.8% (23/68) IgG-positive samples, demonstrating 100% sensitivity and 78.95% specificity compared to the MAYV-specific 50% plaque reduction neutralization assay. In addition, the positive MAYV-neutralizing samples showed high titers of detection by rE2-MAYV ELISA, suggesting a highly sensitive test. The rE2-MAYV ELISA also detected 42.5% (29/68) IgM-positive samples, of which 13.8% (4/29) presented high-avidity interactions with rE2-MAYV. Cross-reactivity was observed with Chikungunya virus (CHIKV)-specific murine antibody sample but not with CHIKV-specific human and other Alphavirus murine antibodies. In short, we have developed a rapid, simple, specific, and sensitive MAYV rE2-ELISA, and our preliminary results show its potential applicability to diagnosis of MAYV infections.
Patterns of objectively assessed sedentary time and physical activity among Japanese workers: a cross-sectional observational study

Objectives To examine patterns of sedentary behaviour and physical activity, among Japanese workers with differing occupational activity types. Design A cross-sectional observational study in 2013–2015. Setting Two local communities in Japan. Participants Full-time workers aged 40–64 years (n=345; 55% men) and who lived in two cities. Main outcome measures From accelerometer data for 7 days, mean overall sedentary time, prolonged bouts of sedentary time and light-and moderate-to vigorous-intensity of physical activity (LPA and MVPA) as a proportion of accelerometer wear time and number of breaks per sedentary hour were identified for four time periods: working hours, workdays, non-work hours and non-workdays. These sedentary behaviour and physical activity measures in the four time periods were examined among workers with four self-attributed occupational activity types (mainly sitting, standing, walking, and physical labour), adjusting for sociodemographic attributes. Diurnal patterns of sedentary behaviour, LPA, and MVPA were examined. Results In working hours, those with a sitting job had significantly more total and prolonged sedentary time (total: p<0.001; prolonged: p<0.01) along with less LPA (p<0.001) and MVPA (p<0.001) and less frequent breaks (p<0.01), compared with those with the three more active job type. Similar differences by job type were found for the whole working day, but not for prolonged sedentary time and breaks. On non-working hours and days, differences in sedentary and physically active patterns by job type were not apparent. Conclusions Occupational activity type is related to overall sedentary time and patterns on working days, but not to leisure-time sitting and activity patterns, which were similar across the sitting, standing, walking, and physical labour occupational activity types.
Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: Large prospective cohort and preliminary meta-analysis

Background We aimed to investigate cortical superficial siderosis as an MRI predictor of lobar intracerebral hemorrhage (ICH) recurrence risk in cerebral amyloid angiopathy (CAA), in a large prospective MRI cohort and a systematic review. Methods We analyzed a single-center MRI prospective cohort of consecutive CAA-related ICH survivors. Using Kaplan–Meier and Cox regression analyses, we investigated cortical superficial siderosis and ICH risk, adjusting for known confounders. We pooled data with eligible published cohorts in a two-stage meta-analysis using random effects models. Covariate-adjusted hazard rations (adj-HR) from pre-specified multivariable Cox proportional hazard models were used. Results The cohort included 240 CAA-ICH survivors (cortical superficial siderosis prevalence: 36%). During a median follow-up of 2.6 years (IQR: 0.9–5.1 years) recurrent ICH occurred in 58 patients (24%). In prespecified multivariable Cox regression models, cortical superficial siderosis presence and disseminated cortical superficial siderosis were independent predictors of increased symptomatic ICH risk at follow-up (HR: 2.26; 95% CI: 1.31–3.87, p = 0.003 and HR: 3.59; 95% CI: 1.96–6.57, p < 0.0001, respectively). Three cohorts including 443 CAA-ICH patients in total were eligible for meta-analysis. During a mean follow-up of 2.5 years (range: 2–3 years) 92 patients experienced recurrent ICH (pooled risk ratio: 6.9% per year, 95% CI: 4.2%–9.7% per year). In adjusted pooled analysis, any cortical superficial siderosis and disseminated cortical superficial siderosis were the only independent predictors associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95% CI: 1.5–3.7; p < 0.0001, and adj-HR: 4.4; 95% CI: 2–9.9; p < 0.0001, respectively). Conclusions In CAA-ICH patients, cortical superficial siderosis presence and extent are the most important MRI prognostic risk factors for lobar ICH recurrence. These results can help guide clinical decision making in patients with CAA.
Learning the payoffs and costs of actions

A set of sub-cortical nuclei called basal ganglia is critical for learning the values of actions. The basal ganglia include two pathways, which have been associated with approach and avoid behavior respectively, and are differentially modulated by dopamine projections from the midbrain. According to the influential opponent actor learning model, these pathways represent learned estimates of the positive and negative consequences (payoffs and costs) of actions. The level of dopamine release controls to what extent payoffs and costs enter the overall evaluation of actions. How the knowledge about payoff and cost is acquired is still an open question, even though many theories describe learning from feedback in the basal ganglia. We examine whether a set of plasticity rules proposed to model reinforcement learning in the pathways of the basal ganglia is suitable to extract payoffs and costs from a reward prediction error signal. First, we determine the result of such learning, both analytically and via simulations, for different reward schedules that feature payoffs and costs. Then, we combine the plasticity rules with a decision rule to examine the emerging effect of dopaminergic modulation on the willingness to work for reward. We find that the plasticity rules are suitable to infer the mean payoffs and costs of actions, if those occur at different moments in time. Successful learning requires differential effects of positive and negative reward prediction errors on the two pathways, and a weak decay of synaptic weights over trials. We also confirm that dopaminergic modulation produces effects on the willingness to work for reward similar to those observed in classical experiments. Author summary The basal ganglia are structures underneath the surface of the vertebrate brain, associated with error driven learning. Much is known about the anatomical and biological features of the basal ganglia; scientists now try to understand the algorithms implemented by these structures. Numerous models aspire to capture the learning functionality, but many of them only cover some specific aspect of the algorithm. Instead of further adding to that pool of partial models, we unify two existing ones - one which captures what the basal ganglia learns, and one that describes the learning mechanism itself. The first model suggests that the basal ganglia keeps track of both positive and negative consequences of frequent opportunities, and weighs these by the motivational state in decisions. It explains how payoff and cost are represented, but not how those representations arise. The other model consists of biologically plausible plasticity rules, which describe how learning takes place, but not how the brain makes use of what is learned. We show that the two theories are compatible. Together, they form a model of learning and decision making that integrates the motivational state as well as the learned payoffs and costs of opportunities.
Hybrid monkey testing: enhancing automated GUI tests with random test generation

Many software projects maintain automated GUI tests that are repeatedly executed for regression testing. Every test run executes exactly the same fixed sequence of steps confirming that the currently tested version shows precisely the same behavior as the last version. The confirmatory approach implemented by these tests limits their ability to find new defects. We therefore propose to combine existing automated regression tests with random test generation. Random test generation creates a rich variety of test steps that interact with the system under test in new, unexpected ways. Enhancing existing test cases with random test steps allows revealing new, hidden defects with little extra effort. In this paper we describe our implementation of a hybrid approach that enhances existing GUI test cases with additional, randomly generated interactions. We conducted an experiment using a mature, widely-used open source application. On average the added random interactions increased the number of visited application windows per test by 23.6% and code coverage by 12.9%. Running the enhanced tests revealed three new defects.
Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

Many skin diseases, including psoriasis and atopic dermatitis, have a neurogenic component. In this regard, bidirectional interactions between components of the nervous system and multiple target cells in the skin and elsewhere have been receiving increasing attention. Neuropeptides released by sensory nerves that innervate the skin can directly modulate functions of keratinocytes, Langerhans cells, dermal dendritic cells, mast cells, dermal microvascular endothelial cells and infiltrating immune cells. As a result, neuropeptides and neuropeptide receptors participate in a complex, interdependent network of mediators that modulate the skin immune system, skin inflammation, and wound healing. In this review, we will focus on recent studies demonstrating the roles of α-melanocyte-stimulating hormone, calcitonin gene-related peptide, substance P, somatostatin, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and nerve growth factor in modulating inflammation and immunity in the skin through their effects on dermal microvascular endothelial cells.
Factors associated with HIV testing among men who have sex with men in Guatemala City

Although men who have sex with men (MSM) have the highest human immunodeficiency virus (HIV) prevalence in Guatemala, prevention efforts have been focused on other vulnerable populations. Respondent-driven sampling was used to recruit 444 MSM in Guatemala City to explore factors related to HIV testing among MSM. About 56% of participants reported HIV testing in the past 12 months, which was associated with a public MSM status (adjusted odds ratio (AOR) 2.08; 95% CI 1.02–4.26), participating in peer HIV prevention intervention (AOR 3.71; 95% CI 1.86–7.43), having at least one casual male partner (AOR 2.16; 95% CI 1.11–4.20), and practicing only insertive anal sex (AOR 3.35; 95% CI 1.59–7.09). Men with comprehensive HIV knowledge (AOR 2.63; 95% CI 1.38–5.02) were also more likely to have been tested. Further interventions in Guatemala targeting the most hidden MSM are needed.
All Levels of Providers Can Effectively and Efficiently Teach Pelvic Floor Strength Assessment at Time of Pelvic Examination

Objective In women who undergo provider-guided vaginal biofeedback of pelvic floor muscle strength, we sought to determine whether the level of the provider correlates with the patient’s ability to achieve adequate pelvic floor muscle contractions (PFMCs). Methods From August 2017 to April 2018, patients from 2 urogynecology clinics were recruited to participate in an institutional review board–approved, prospective study examining PFMCs. Pelvic examination and teaching session were done by providers who had specific training on how to assess pelvic floor muscle strength using the validated, modified Oxford scale. Patients were asked to perform a baseline PFMC during a 2-digit pelvic examination. Thereafter, patients were counseled to relax their muscles, identify the levator ani muscles during provider teaching, and perform 3 consecutive provider-guided PFMCs. The strength of each PFMC was measured, and the time-to-teach (TTT) was recorded. The level of provider and TTT were correlated with PFMC1 to PFMC3 using Spearman correlation coefficient. Results One hundred women participated. Obstetrics/gynecology (OB/GYN) residents (post-graduate years 1–4) evaluated 20 patients; female pelvic medicine and reconstructive surgery fellowship trainees (post-graduate years 5–7), 38 patients; OB/GYN nurse practitioners, 18 patients; generalist OB/GYN faculty, 9 patients; and female pelvic medicine and reconstructive surgery faculty, 15 patients. There was no correlation between level of provider and TTT or between level of provider and strength of PFMC1, PFMC2, or PFMC3. Conclusions At the time of pelvic floor muscle assessment, the level of provider does not impact teaching time or PFMC1 to PFMC3. Teaching pelvic floor muscle exercise is a cost-effective, low-resource tool to improve patient care, and providers of any level should be encouraged to teach pelvic floor muscle exercise to patients at the time of office examination.
A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, has been confirmed to possess excellent antibacterial activity against Gram-positive bacteria. To illustrate the pharmacokinetic profile after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations with DPTM, as well as tissue distribution and excretion via urine and feces in vivo, a specific, sensitive and robust HPLC-MS/MS method was first developed to determine DPTM in rat plasma, various tissues, urine and feces. The plasma, tissues, urine and feces samples were treated by protein precipitation with acetonitrile using tiamulin fumarate as an internal standard (IS). This method which was achieved on an HPLC system detector equipped with an ESI interface, was sensitive with 5 ng/mL as the lower limit of detection and exhibited good linearity (R2 > 0.9900) in the range of 5–4000 ng/mL for plasma, various tissues, urine and feces, as well as intra-day precision, inter-day precision and accuracy. The matrix effects ranged from 94.2 to 109.7% with RSD ≤ 9.4% and the mean extraction recoveries ranged from 95.4 to 109.5% in plasma, tissue homogenates, urine and feces (RSD ≤ 9.9). After i.v. , i.m. and p.o. administrations, DPTM was rapidly absorbed and metabolized in rats with the half-life (t1/2) of 1.70–1.86, 3.23–3.49 and 4.38–4.70 for 10, 25 and 75 mg/kg doses, respectively. The tissue distribution showed that DPTM was diffused into all the tested tissues, especially into the intestine and lung. Excretion via urine and feces studies demonstrated that DPTM was mainly excreted by feces after administration.
Rural-urban disparities in missed opportunities for vaccination in sub-Saharan Africa: a multi-country decomposition analyses

ABSTRACT Background: In this study, we aimed to explore the rural-urban disparities in the magnitude and determinants of missed opportunities for vaccination (MOV) in sub-Saharan Africa. Methods: This was a cross-sectional study using nationally representative household surveys conducted between 2007 and 2017 in 35 countries across sub-Saharan Africa. The risk difference in MOV between rural or urban dwellers were calculated. Logistic regression method was used to investigate the urban-rural disparities in multivariable analyses. Then Blinder-Oaxaca method was used to decompose differences in MOV between rural and urban dwellers. Results: The median number of children aged 12 to 23 months was 2113 (Min: 370, Max: 5896). There was wide variation in the the magnitude of MOV among children in rural and urban areas across the 35 countries. The magnitude of MOV in rural areas varied from 18.0% (95% CI 14.7 to 21.4) in the Gambia to 85.2% (81.2 to 88.9) in Gabon. Out of the 35 countries included in this analysis, pro-rural inequality was observed in 16 countries (i.e. MOV is prevalent among children living in rural areas) and pro-urban inequality in five countries (i.e. MOV is prevalent among children living in urban areas). The contributions of the compositional ‘explained’ and structural ‘unexplained’ components varied across the countries. However, household wealth index was the most frequently identified factor. Conclusions: Variation exists in the level of missed opportunities for vaccination between rural and urban areas, with widespread pro-rural inequalities across Africa. Although several factors account for these rural-urban disparities in various countries, household wealth was the most common.
Categorization and Characterization of Activities Designed to Help Health-care Professionals Involved in Hepatitis Care Increase Their Awareness of the Disease: The Classification of Hepatitis Medical Care Coordinators

Objective This study aimed to investigate the current state of the activities performed by hepatitis medical care coordinators, categorize coordinators according to the activities they perform, and determine the backgrounds of these coordinators. Methods A self-administered questionnaire survey was completed by 414 coordinators. The surveyed items included gender, occupation, activity items performed, and barriers that inhibited the performance of these activities. A hierarchical cluster analysis was applied, and cases were classified based on the contents of the activities in question. Results The coordinators were classified into four groups (A-D). Group A, consisting primarily of public health nurses, was classified as “the type that conducted activities aimed at providing information and recommendations. ” Group B, which included registered dieticians and clerks, was classified as “the type that uses multidisciplinary collaboration to perform their tasks. ” Group C, which included clinical nurses, was classified as “the type that was more likely to perform activities as leaders in an organization. ” Group D, consisting primarily of pharmacists, was classified as “the type that promoted activities centered on providing instructions regarding medication dosage and administration. ” Conclusion Our study showed that coordinators' professional skills and abilities are reflected in the contents of the activities they conduct, and that, to adequately perform their roles, they must acquire skills in addition to those required in their original occupations. To implement high-quality hepatitis countermeasures, there is a need to foster an environment that facilitates cooperation between coordinators, as well as relationship-building.
Intravitreal Injections of Voriconazole for Candida Endophthalmitis: A Case Series

ABSTRACT Purpose: Candida endophthalmitis represents a therapeutic challenge, considering the inability of many antifungals to achieve adequate concentrations in the vitreous. Intravitreal injection (IVI) of antifungals (amphotericin b deoxycholate or voriconazole) is therefore recommended. Whereas amphotericin b IVI is well documented, clinical data on voriconazole IVI are limited. Methods: This was a retrospective review IRB approved of patients receiving voriconazole IVI for Candida endophthalmitis. Complete ophthalmological examination was completed at baseline and during follow-up. Results: Five patients were treated with a mean four injections [range: 2–9] of voriconazole (100 µg/0.1 mL saline). Improvement of visual acuity and disappearance of signs of infection were obtained in all patients. Safety concern including photoreceptor toxicity was not attributed to voriconazole IVI. Conclusions: Voriconazole IVI demonstrated to be safe and led to a favorable clinical outcome. Thus, voriconazole IVI must be performed if Candida endophthalmitis is suspected to increase the chance of clinical success.
Renal control of disease tolerance to malaria

Significance Malaria, the disease caused by Plasmodium spp. infection, remains a major global cause of morbidity and mortality, claiming the lives of over ∼4.5 × 105 individuals per year. Paradoxically, however, up to 98% of infected individuals survive the infection, establishing disease tolerance to malaria. We found that this host defense strategy, which does not target Plasmodium directly, relies on the capacity of renal proximal tubule epithelial cells to detoxify labile heme, a pathologic by-product of hemolysis that accumulates in plasma and urine during the blood stage of infection. This defense strategy prevents the onset of acute kidney injury, a clinical hallmark of severe malaria. Malaria, the disease caused by Plasmodium spp. infection, remains a major global cause of morbidity and mortality. Host protection from malaria relies on immune-driven resistance mechanisms that kill Plasmodium. However, these mechanisms are not sufficient per se to avoid the development of severe forms of disease. This is accomplished instead via the establishment of disease tolerance to malaria, a defense strategy that does not target Plasmodium directly. Here we demonstrate that the establishment of disease tolerance to malaria relies on a tissue damage-control mechanism that operates specifically in renal proximal tubule epithelial cells (RPTEC). This protective response relies on the induction of heme oxygenase-1 (HMOX1; HO-1) and ferritin H chain (FTH) via a mechanism that involves the transcription-factor nuclear-factor E2-related factor-2 (NRF2). As it accumulates in plasma and urine during the blood stage of Plasmodium infection, labile heme is detoxified in RPTEC by HO-1 and FTH, preventing the development of acute kidney injury, a clinical hallmark of severe malaria.