Miracle-dz/UniFAR-FTUs huggingface dataset:
The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia

Primary cilia are crucial for signal transduction in a variety of pathways, including hedgehog and Wnt. Disruption of primary cilia formation (ciliogenesis) is linked to numerous developmental disorders (known as ciliopathies) and diseases, including cancer. The ubiquitin–proteasome system (UPS) component UBR5 was previously identified as a putative positive regulator of ciliogenesis in a functional genomics screen. UBR5 is an E3 ubiquitin ligase that is frequently deregulated in tumors, but its biological role in cancer is largely uncharacterized, partly due to a lack of understanding of interacting proteins and pathways. We validated the effect of UBR5 depletion on primary cilia formation using a robust model of ciliogenesis, and identified CSPP1, a centrosomal and ciliary protein required for cilia formation, as a UBR5-interacting protein. We show that UBR5 ubiquitylates CSPP1, and that UBR5 is required for cytoplasmic organization of CSPP1-comprising centriolar satellites in centrosomal periphery, suggesting that UBR5-mediated ubiquitylation of CSPP1 or associated centriolar satellite constituents is one underlying requirement for cilia expression. Hence, we have established a key role for UBR5 in ciliogenesis that may have important implications in understanding cancer pathophysiology.
Mixed-methods research: Integrating qualitative and quantitative approaches to the psychological study of culture.

book series. Evidence-based psychological practice with ethnic minorities: Culturally informed research and clinical strategies (p. 147–167). Copyright 2016 by the American Psychological Association. Reproduced with permission. https://doi.org/10.1037/14940-008© American Psychological Association, 2016. This paper is not the copy of record and may not exactly replicate the authoritative document published in the APA journal. Please do not copy or cite without author’s permission. The final article is available, upon publication, at: https://doi.org/10.1037/14940-008
Attendance of children and adolescents with psychoactive substance use disorders performed by Psychosocial Care Centers in Brazil, 2008-2012.

OBJECTIVE to describe the profile of care for children and adolescents withpsychoactive substance use disorders performed by the Brazilian Psychosocial Care Centers (Centros de Atenção Psicossocial - CAPS) from 2008 to 2012. METHODS a descriptive study with data from the SUS Outpatient Information System (Sistema de Informações Ambulatoriais do Sistema Único de Saúde - SIA/SUS) and the system of National Registration of Health Establishments (Cadastro Nacional de Estabelecimentos de Saúde - CNES). RESULTS a total of 151.330 attendances were observed, 81.2% were males and 99.2% were in the age range of 10 to 19 years; the main causes were polydrug use (56.7%), cocaine (15.6%), marijuana (15.6%) and alcohol (9.0%); the CAPS for Alcohol and other Drugs (CAPS AD) accounted for 81.8% of the records; from 2008 to 2012, the attendance rate from 39.6 to 76.7/100 thousand inhabitants. CONCLUSION there was an increase in the attendance rates, observing the predominance of males, age range of 10 to 19 years and disorders due to polydrug use.
Moiré Photo Restoration Using Multiresolution Convolutional Neural Networks

Digital cameras and mobile phones enable us to conveniently record precious moments. While digital image quality is constantly being improved, taking high-quality photos of digital screens still remains challenging because the photos are often contaminated with moiré patterns, a result of the interference between the pixel grids of the camera sensor and the device screen. Moiré patterns can severely damage the visual quality of photos. However, few studies have aimed to solve this problem. In this paper, we introduce a novel multiresolution fully convolutional network for automatically removing moiré patterns from photos. Since a moiré pattern spans over a wide range of frequencies, our proposed network performs a nonlinear multiresolution analysis of the input image before computing how to cancel moiré artefacts within every frequency band. We also create a large-scale benchmark data set with 1 00 000+ image pairs for investigating and evaluating moiré pattern removal algorithms. Our network achieves the state-of-the-art performance on this data set in comparison to existing learning architectures for image restoration problems.
Sustained Immune Control in HBeAg-Positive Patients who Switched from Entecavir Therapy to Pegylated Interferon-α2a: 1 Year follow-up of the OSST Study

Background In the OSST study, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients who switched from long-term entecavir (ETV) therapy to pegylated interferon-α2a (PEG-IFN-α2a; 40 kDa) achieved higher rates of HBeAg seroconversion and hepatitis B surface antigen (HBsAg) loss than those who continued ETV. Herein we report the sustainability of serological responses during 1 year of untreated follow-up in patients who switched from ETV to PEG-IFN-α2a therapy. Methods A total of 62 patients who completed 48 weeks of PEG-IFN-α2a therapy were followed-up for 48 weeks off treatment. Primary end points were HBeAg seroconversion and maintenance of HBeAg seroconversion at 48 weeks post-treatment. Secondary end points included HBsAg loss, HBV DNA <1,000 copies/ml and alanine aminotransferase normalization (<1 x upper limit of normal). Results The HBeAg seroconversion rate increased from 17.7% (11/62) at the end of treatment to 38.7% (24/62) 1 year post-treatment. Sustained HBeAg seroconversion was achieved by 63.6% (7/11) patients with end-of-treatment responses, while late HBeAg seroconversion was achieved by 33.3% (17/51) of patients who did not have end-of-treatment responses. Sustained HBsAg loss was documented in 6 of 7 patients, and sustained HBV DNA suppression was achieved in 60% (27/45) of patients with an end-of-treatment response. Conclusions In patients who do not achieve HBeAg sero-conversion during long-term ETV therapy, switching to finite treatment with PEG-IFN-α2a produces HBeAg sero-conversion in a substantial proportion of patients at end of treatment and during 1 year of follow-up. Moreover, HBeAg seroconversion and HBsAg loss are sustained in most patients during 1 year of untreated follow-up.
The MOCHA DM study: The Effect Of MOmordica CHArantia Tablets on Glucose and Insulin Levels During the Postprandial State Among Patients with Type 2 Diabetes Mellitus*

4Resident, Department of Medicine, UP-Philippine General Hospital Background: The worldwide prevalence of diabetes is rising both in developed and developing countries like the Philippines where 4.6% of the population has the disease. Because of the high cost of medications, the use of dietary supplements has also increased. Momordica charantia (ampalaya), is a well known plant with glucoselowering properties which have been demonstrated by previous clinical studies. Its mechanism of action and pharmacologic properties are not yet well understood, and hence continues to be used as a supplement rather than as a standard drug for the treatment of Type 2 diabetes.
Effects of Endurance-Focused Physical Activity Interventions on Brain Health

Physical activity intervention studies that focus on improving cognitive function in older adults have increasingly used magnetic resonance imaging (MRI) measures in addition to neurocognitive measures to assess effects on the brain. The purpose of this systematic review was to identify the effects of endurance-focused physical activity randomized controlled trial (RCT) interventions on the brain as measured by MRI in community-dwelling middle-aged or older adults without cognitive impairment. Five electronic databases were searched. The final sample included six studies. None of the studies reported racial or ethnic characteristics of the participants. All studies included neurocognitive measures in addition to MRI. Five of the six interventions included laboratory-based treadmill or supervised bike exercise sessions, while one included community-based physical activity. Physical activity measures were limited to assessment of cardiorespiratory fitness and, in one study, pedometer. Due to the lack of adequate data reported, effect sizes were calculated for only one study for MRI measures and two studies for neurocognitive measures. Effect sizes ranged from d = . 2 to . 3 for MRI measures and . 2 to . 32 for neurocognitive measures. Findings of the individual studies suggest that MRI measures may be more sensitive to the effects of physical activity than neurocognitive measures. Future studies are needed that include diverse, community-based participants, direct measures of physical activity, and complete reporting of MRI and neurocognitive findings.
Individualized Cognitive Rehabilitation for Adults with Acquired Brain Injury

Page 5 INTRODUCTION a. Acquired Brain Injury b. Attention i. Definition and Identification of Domains ii. Neural Correlates iii. Relationship between Attention and ABI c. Executive Function i. Definition ii. Neural Correlates iii. Relationship between Executive Function and ABI d. Prospective Memory i. Define ii. Neural Correlates iii. Relationship between PM and ABI e. Validity of Study Page 6 METHODS a. Recruitment b. Assessment Tools i. Measures of Generalization ii. Neuropsychological Assessments iii. Memory for Intentions Screening Test c. Cognitive Rehabilitation i. Rote Repetition PM Training ii. Attention Process Training d. Data Collection & Analyses Page 14 PARTICIPANTS & INDIVIDUALIZED PROTOCOLS a. Participant 1 i. Case Presentation ii. Protocol iii. Rote Repetition PM Training iv. Results b. Participant 2 i. Case Presentation ii. Protocol iii. Attention Process Training iv. APT Results c. Participant 3 i. Case Presentation ii. Protocol Page 19 DISCUSSION a. Interpretation of Results b. Study Limitations c. Future Directions Page 32 REFERENCES Page 37 Cognitive Rehabilitation in ABI
A phylogeographic investigation of the kelp genus Laminaria (Laminariales, Phaeophyceae), with emphasis on the South Atlantic Ocean

The genus Laminaria has a wide distribution range compared with other kelp genera because it is found in both the North and the South Atlantic, on both sides of the North Pacific, as well as in the Mediterranean. Hypotheses behind this biogeographical pattern have been discussed by several authors but have not yet been fully evaluated with time‐calibrated phylogenies. Based on the analysis of four molecular markers (ITS2, rbcL, atp8 and trnWI), our goal was to reassess the Laminaria species diversity in South Africa, assess its relationship with the other species distributed in the South Atlantic and reconstruct the historical biogeography of the genus. Our results confirm the occurrence of a single species, L. pallida, in southern Africa, and its sister relationship with the North Atlantic L. ochroleuca. Both species belonged to a clade containing the other South Atlantic species: L. abyssalis from Brazil, and the Mediterranean L. rodriguezii. Our time‐calibrated phylogenies suggest that Laminaria originated in the northern Pacific around 25 mya, followed by at least two migration events through the Bering Strait after its opening (~5.32 mya). Today, the first is represented by L. solidungula in the Arctic, while the second gave rise to the rest of the Atlantic species. The colonization of the North Atlantic was followed by a gradual colonization southward along the west coast of Europe, into the Mediterranean (~2.07 mya) and two recent, but disconnected, migrations (~1.34 and 0.87 mya) across the equator, giving rise to L. abyssalis in Brazil and L. pallida in southern Africa, respectively.
The Impact of Ribavirin Plasma Concentration on the Efficacy of the Interferon-Sparing Regimen, Sofosbuvir and Ribavirin

Background Ribavirin augments sustained virological response when administered with pegylated interferon for the treatment of chronic HCV infection. The impact of ribavirin plasma concentration on outcome in individuals receiving interferon-free regimens has not been evaluated. Methods Stored plasma samples were retrieved for 47 treatment-naive subjects who received sofosbuvir and weight-based ribavirin for 12–24 weeks in the Phase IIb QUANTUM study. Week 1, 4 and 8 ribavirin plasma concentrations (mg/l) were quantified using high-performance liquid chromatography with UV detection. Results Sustained virological response at 12 weeks post treatment was observed in 55% with all treatment failures due to relapse. The median ribavirin plasma concentration increased from week 1 (1.58 mg/l, IQR 1.44–2.24) to week 4 (2.23 mg/l, IQR 1.69–2.87) and week 8 (2.67 mg/l, IQR 2.10–3.26) with wide variability at steady state. Median week 4 ribavirin plasma concentration was 2.25 mg/l (IQR 1.63–3.05) in those with a sustained virological response as compared to 2.07 mg/l (IQR 1.79–2.86) in those with treatment failure (OR 1.35; 95% CI 0.76, 2.39; P=0.3). No significant association between ribavirin plasma concentration and treatment response was noted at weeks 1 or 8. Conclusions We found no evidence of an association between ribavirin plasma concentrations and relapse suggesting that, as opposed to interferon-based therapy, suboptimal ribavirin plasma concentrations did not explain the high rate of virological failure with this regimen. Our findings suggest that in interferon-free ribavirin-containing regimens, concerns over ribavirin dosing to achieve previously determined target plasma concentrations are unnecessary.
Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models

Endometriosis is an estrogen (ER)-dependent gynecological disease caused by the growth of endometrial tissue at extrauterine sites. Current endocrine therapies address the estrogenic aspect of disease and offer some relief from pain but are associated with significant side effects. Immune dysfunction is also widely believed to be an underlying contributor to the pathogenesis of this disease. This study evaluated an inhibitor of c-Jun N-terminal kinase, bentamapimod (AS602801), which interrupts immune pathways, in 2 rodent endometriosis models. Treatment of nude mice bearing xenografts biopsied from women with endometriosis (BWE) with 30 mg/kg AS602801 caused 29% regression of lesion. Medroxyprogesterone acetate (MPA) or progesterone (PR) alone did not cause regression of BWE lesions, but combining 10 mg/kg AS602801 with MPA caused 38% lesion regression. In human endometrial organ cultures (from healthy women), treatment with AS602801 or MPA reduced matrix metalloproteinase-3 (MMP-3) release into culture medium. In organ cultures established with BWE, PR or MPA failed to inhibit MMP-3 secretion, whereas AS602801 alone or MPA + AS602801 suppressed MMP-3 production. In an autologous rat endometriosis model, AS602801 caused 48% regression of lesions compared to GnRH antagonist Antide (84%). AS602801 reduced inflammatory cytokines in endometriotic lesions, while levels of cytokines in ipsilateral horns were unaffected. Furthermore, AS602801 enhanced natural killer cell activity, without apparent negative effects on uterus. These results indicate that bentamapimod induced regression of endometriotic lesions in endometriosis rodent animal models without suppressing ER action. c-Jun N-terminal kinase inhibition mediated a comprehensive reduction in cytokine secretion and moreover was able to overcome PR resistance.
UvA-DARE ( Digital Academic Repository ) What are the odds of anxiety disorders running in families ?

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The enamel protein ODAM promotes mineralization in a collagen matrix

ABSTRACT Purpose/aim of the study: Odontogenic ameloblast-associated protein (ODAM) is predominantly expressed during the maturation stage of enamel formation and interacts strongly with amelotin (AMTN). AMTN is involved in enamel mineralization, but the effect of ODAM on mineralization has not been investigated. This study determined whether ODAM was able to induce hydroxyapatite (HA) mineralization in modified simulated body fluid (SBF) and in a collagen matrix in vitro. Materials and methods: To monitor the kinetics of calcium phosphate mineralization, recombinant human (rh) ODAM protein in SBF buffer was incubated at 37°C and a light-scattering assay was conducted at intervals. To investigate the nucleation of ODAM in collagen matrix, the ODAM-impregnated collagen hydrogel was incubated in SBF buffer for 24 hours. Bovine serum albumin (BSA) was used as negative control. Mineral deposits were visualized using electron microscopy. Results: The presence of rh-ODAM protein in SBF resulted in higher light-scattering values after 18–24 hours. Calcium phosphate precipitates were observed on the surface of the ODAM-treated, but not BSA-treated collagen hydrogel after 24 hours in SBF. TEM and SAED analyses showed that these crystals consisted of needle-like HA. Conclusion: Similar to AMTN, ODAM is able to promote HA nucleation in a dose-dependent manner in SBF, and even outside of its biological context in vitro.
Lessons from my undergraduate research students

From very early on, my personal/professional life has been shaped by teachers in many different settings. Teaching and learning form a two-way street. In the process of teaching undergraduate students, particularly in the research lab, I have learned some profound lessons about the importance of listening to them, challenging them, giving them autonomy, and allowing them to enjoy success and to risk failure. I am now working with a team of faculty members to implement these lessons in a course-based undergraduate research experience in the biochemistry teaching laboratory. Our goal is to seek answers to the question “How do students become scientists? ” and to implement those answers with our future students.
Revista De Cercetare [i Interven]ie Social\ the Role of Internal and External Social Capital in Crowdfunding: Evidence from China the Role of Internal and External Social Capital in Crowdfunding: Evidence from China

How does a proponent's internal and external social capital impact crowdfunding performance? Based on the theory of social capital, we developed a research model and conducted an econometric analysis using the objective data collected from a Chinese comprehensive crowdfunding platform, ZhongchouNet. Results of an econometric analysis of a sample of 862 projects show that two types of the proponent's external social capital have significant effect on crowdfunding performance alone. Moreover, the effect of internal and external social capital on the success of a campaign is fully moderated by the type of the project. These results suggest that, to improve crowdfunding performance, the proponents, especially proponents of for-profit projects, should make good use of the mechanisms of social capital construction existed inside the crowdfunding platform.
The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience’s MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1–9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.
Pharmacokinetic Monitoring of Vancomycin in Cystic Fibrosis: Is It Time to Move Past Trough Concentrations?

Background: A correlation between vancomycin (VAN) trough concentrations (VTC) and area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC/MIC) has not been established in children/adolescents with cystic fibrosis (CF). The primary objective of this study was to determine the correlation between measured VTCs and AUC/MIC using population-based pharmacokinetics. Methods: A retrospective cohort study of children/adolescents diagnosed with CF, 6 to <18 years of age, treated with VAN for methicillin-resistant Staphylococcus aureus infection was conducted. The relationship between final VTCs and calculated AUC/MIC was assessed using Pearson and Spearman correlations. All tests were 2-tailed with alpha set at 0.05. Results: Thirty children/adolescents, 7 to 17 years of age (median age 15 year; interquartile range: 9–17 years), were included. The mean final VAN dose was 58.03 ± 18.58 mg/kg/d, and the median final VTC was 12.6 (11–13.6) mg/L. The mean AUC/MIC was 355.34 ± 138.46 (Le model) versus 426.79 ± 178.92 (Stockmann model; P = 0.089). No correlation existed between VTCs and AUC/MIC using either the model by Le (r = 0.140; P = 0.461) or Stockmann (r = 0.115; P = 0.564). Using the Stockmann model, VAN dose (mg/kg/dose) was found to have a strong positive correlation with AUC (r = 0.8874; P < 0.0001) and AUC/MIC (r = 0.7877; P < 0.0001). Conclusions: VTCs did not correlate with AUC or AUC/MIC. Further research is needed to determine which estimate of VAN treatment efficacy is most appropriate for children and adolescents with CF infected with methicillin-resistant Staphylococcus aureus.