Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes

Amutation in the small GTPase Rab38 gives rise to the mouse coat color phenotype “chocolate” (cht), implicating Rab38 in the regulation of melanogenesis. However, its role remains poorly characterized. We report that cht Rab38G19V is inactive and that the nearly normal pigmentation in cht melanocytes results from functional compensation by the closely related Rab32. In cht cells treated with Rab32-specific small interfering RNA, a dramatic loss of pigmentation is observed. In addition to mature melanosomes, Rab38 and Rab32 localize to perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1, consistent with a role in the intracellular sorting of these proteins. In Rab38/Rab32-deficient cells, tyrosinase appears to be mistargeted and degraded after exit from the trans-Golgi network (TGN). This suggests that Rab38 and Rab32 regulate a critical step in the trafficking of melanogenic enzymes, in particular, tyrosinase, from the TGN to melanosomes. This work identifies a key role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of melanosomes and potentially other lysosome-related organelles.
Efficacy and safety of endostar® combined with chemotherapy in patients with advanced soft tissue sarcomas.

BACKGROUND Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. OBJECTIVE To evaluate the efficacy and safety of Endostar® combined with chemotherapy in patients with advanced STS. METHODS A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar® were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. RESULTS In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P = 0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P = 0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. CONCLUSIONS Endostar® combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.
Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, 68Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)]) was developed as a PSMA ligand. The aim of this study was to investigate the detection rate of 68Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. Methods: Two hundred forty-eight of 393 patients were evaluable for a retrospective analysis. Median prostate-specific antigen (PSA) level was 1.99 ng/mL (range, 0.2–59.4 ng/mL). All patients underwent contrast-enhanced PET/CT after injection of 155 ± 27 MBq of 68Ga-PSMA ligand. The detection rates were correlated with PSA level and PSA kinetics. The influence of antihormonal treatment, primary Gleason score, and contribution of PET and morphologic imaging to the final diagnosis were assessed. Results: Two hundred twenty-two (89.5%) patients showed pathologic findings in 68Ga-PSMA ligand PET/CT. The detection rates were 96.8%, 93.0%, 72.7%, and 57.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, and 0.2 to <0.5 ng/mL, respectively. Whereas detection rates increased with a higher PSA velocity (81.8%, 82.4%, 92.1%, and 100% in <1, 1 to <2, 2 to <5, and ≥5 ng/mL/y, respectively), no significant association could be found for PSA doubling time (82.7%, 96.2%, and 90.7% in >6, 4–6, and <4 mo, respectively). 68Ga-PSMA ligand PET (as compared with CT) exclusively provided pathologic findings in 81 (32.7%) patients. In 61 (24.6%) patients, it exclusively identified additional involved regions. In higher Gleason score (≤7 vs. ≥8), detection efficacy was significantly increased (P = 0.0190). No significant difference in detection efficacy was present regarding antiandrogen therapy (P = 0.0783). Conclusion: Hybrid 68Ga-PSMA ligand PET/CT shows substantially higher detection rates than reported for other imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA values (<0.5 ng/mL), which in many cases can substantially influence the further clinical management.
On Modeling Life

We present a theoretical as well as experimental investigation of a population of self-replicating segments of code subject to random mutation and survival of the fittest. Under the assumption that such a system constitutes a minimal system with characteristics of life, we obtain a number of statements on the evolution of complexity and the trade-off between entropy and information.
The acid/base profile of agrochemicals

Abstract Drug-likeness has long been studied in the pursuit of finding new medicines. Similarly, in the agrochemical field there is value in exploring the properties of the chemicals involved. Patterns that emerge can potentially influence future discovery campaigns to improve the probability of commercial success. In this study we investigate the acid/base properties and physicochemical characteristics of three classes of compounds: fungicides, herbicides and insecticides. In comparison with FDA-approved drugs, it was noted that the pesticides were generally smaller, possessed a neutral charge state and were more lipophilic. The results are discussed in the light of their intended targets.
CBOS: Continuos bag of sentences for learning sentence embeddings

There has been recent work learning distributed sentence representations, which utilise neighbouring sentences as context for learning the embedding of a sentence. The setting is reminiscent of training word embeddings, yet no work has reported a baseline using the same training objective as learning word vectors. We fill this gap by empirically investigating the use of a Continuous Bag-of-Word (CBOW) objective, predicting the current sentence using its context sentences. We name this method a Continuous Bag-of-Sentences (CBOS) method. Results on standard benchmark show that CBOS is a highly competitive baseline for training sentence embeddings, outperforming most existing methods for text similarity measurement.
Living with an indwelling urethral catheter in a community setting: Exploring triggers for unscheduled community nurse “out‐of‐hours” visits

AIMS AND OBJECTIVE To explore the experiences of community patients living with a urethral catheter and those caring for them. BACKGROUND Living at home with an indwelling urethral catheter often results in consequences that create a double-edged burden: first, on patients and their relative carers and second, in terms of unscheduled community nurse service "out-of-hours" provision. DESIGN One-to-one interviews were conducted with patients living at home, their relative carers, qualified community nurses, augmented home carers and healthcare assistant. Quantitative data in relation to frequency, duration and reason for visits were extracted from the community nurse "out-of-hours" service database. RESULTS Quantitative data showed that 20% of all community nurses unscheduled "out-of-hours" visits were triggered by an indwelling urethral catheter consequence. Qualitative data revealed that health and social care staff felt knowledgeable and skilled in urethral catheter management. Conversely, patients and relative carers felt poorly equipped to manage the situation when something went wrong. The majority of patients described the catheter as being a debilitating source of anxiety and pain that reduced their quality of life. CONCLUSION Urethral catheter complications are frequent and impact seriously on quality of life with informal carers also affected. Community nurses experienced frequent unscheduled visits. Patients often feel isolated as well as lacking in knowledge, skills and information on catheter management. Having better urethral catheter information resources could increase patient and relative carer confidence, encourage self-care and problem solving, as well as facilitate meaningful consistent dialogue between patients and those who provide them with help and support. RELEVANCE TO CLINICAL PRACTICE Better patient information resources regarding urethral catheter management have potential to improve patient and relative carer quality of life and reduce service provision burden.
Validation of a Latent Construct for Dementia in a Population-Wide Dataset from Singapore.

BACKGROUND The latent variable δ has been proposed as a proxy for dementia. Previous validation studies have been conducted using convenience samples. It is currently unknown how δ performs in population-wide data. OBJECTIVE To validate δ in Singapore using population-wide epidemiological study data on persons aged 60 and above. METHODS δ was constructed using items from the Community Screening Instrument for Dementia (CSI'D) and World Health Organization Disability Assessment Schedule (WHODAS II). Confirmatory factor analysis (CFA) was conducted to examine δ model fit. Convergent validity was examined with the Clinical Dementia Rating scale (CDR) and GMS-AGECAT dementia. Divergent validity was examined with GMS-AGECAT depression. RESULTS The δ model demonstrated fit to the data, χ2(df) = 249.71(55), p < 0.001, CFI = 0.990, TLI = 0.997, RMSEA = 0.037. Latent variable δ was significantly associated with CDR and GMS-AGECAT dementia (range: β= 0.32 to 0.63), and was not associated with GMS-AGECAT depression. Compared to unadjusted models, δ model fit was poor when adjusted for age, gender, ethnicity, and education. CONCLUSION The study found some support for δ as a proxy for dementia in Singapore based on population data. Both convergent and divergent validity were established. In addition, the δ model structure appeared to be influenced by age, gender, ethnicity, and education covariates.
Tolerance to mild salinity stress in japonica rice: A genome-wide association mapping study highlights calcium signaling and metabolism genes

Salinity tolerance is an important quality for European rice grown in river deltas. We evaluated the salinity tolerance of a panel of 235 temperate japonica rice accessions genotyped with 30,000 SNP markers. The panel was exposed to mild salt stress (50 mM NaCl; conductivity of 6 dS m-1) at the seedling stage. Eight different root and shoot growth parameters were measured for both the control and stressed treatments. The Na+ and K+ mass fractions of the stressed plants were measured using atomic absorption spectroscopy. The salt treatment affected plant growth, particularly the shoot parameters. The panel showed a wide range of Na+/K+ ratio and the temperate accessions were distributed over an increasing axis, from the most resistant to the most susceptible checks. We conducted a genome-wide association study on indices of stress response and ion mass fractions in the leaves using a classical mixed model controlling structure and kinship. A total of 27 QTLs validated by sub-sampling were identified. For indices of stress responses, we also used another model that focused on marker × treatment interactions and detected 50 QTLs, three of which were also identified using the classical method. We compared the positions of the significant QTLs to those of approximately 300 genes that play a role in rice salt tolerance. The positions of several QTLs were close to those of genes involved in calcium signaling and metabolism, while other QTLs were close to those of kinases. These results reveal the salinity tolerance of accessions with a temperate japonica background. Although the detected QTLs must be confirmed by other approaches, the number of associations linked to candidate genes involved in calcium-mediated ion homeostasis highlights pathways to explore in priority to understand the salinity tolerance of temperate rice.
Gendered childcare norms — evidence from rural Swaziland to inform innovative structural HIV prevention approaches for young women

Addressing discriminatory gender norms is a prerequisite for preventing HIV in women, including young women. However, the gendered expectation that women will perform unpaid childcare-related labour is rarely conceptualised as influencing their HIV risk. Our aim was to learn from members of a rural Swazi community about how gendered childcare norms. We performed sequential, interpretive analysis of focus group discussion and demographic survey data, generated through participatory action research. The results showed that gendered childcare norms were firmly entrenched and intertwined with discriminatory norms regarding sexual behaviour. Participants perceived that caring for children constrained young women’s educational opportunities and providing for children’s material needs increased their economic requirements. Some young women were perceived to engage in “transactional sex” and depend financially on men, including “sugar daddies”, to provide basic necessities like food for the children they cared for. Our results suggested that men were no longer fulfilling their traditional role of caring for children’s material needs, despite women’s traditional role of caring for their physical and emotional needs remaining firmly entrenched. The results indicate that innovative approaches to prevent HIV in young women should incorporate structural approaches that aim to transform gendered norms, economically empower women and implement policies guaranteeing women equal rights.
HIV stigma trends in the general population during antiretroviral treatment expansion: analysis of 31 countries in sub-Saharan Africa, 2003–2013

Background:HIV-related stigma is associated with increased risk-taking behavior, reduced uptake of HIV testing, and decreased adherence to antiretroviral therapy (ART). Although ART scale-up may reduce HIV-related stigma, the extent to which levels of stigma in the general population have changed during the era of ART scale-up in sub-Saharan Africa is unknown. Methods:Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 31 African countries between 2003 and 2013. We fitted multivariable linear regression models with cluster-correlated robust standard errors and country fixed effects, specifying social distance or anticipated stigma as the dependent variable and year as the primary explanatory variable of interest. Results:We estimated a statistically significant negative association between year and desires for social distance (b = −0.020; P < 0.001; 95% confidence interval: −0.026 to −0.015) but a statistically significant positive association between year and anticipated stigma (b = 0.023; P < 0.001; 95% confidence interval: 0.018 to 0.027). In analyses stratified by HIV prevalence above or below the sample median, declines in social distancing over time were more pronounced among countries with a higher HIV prevalence. Conclusions:Concomitant with ART scale-up in sub-Saharan Africa, anticipated stigma in the general population increased despite a decrease in social distancing toward people living with HIV. Although ART scale-up may help reduce social distancing toward people living with HIV, particularly in high-prevalence countries, other interventions targeting symbolic or instrumental concerns about HIV may be needed.
MINVDD testing for weak CMOS ICs

A weak chip is one that contains flaws-defects that do not interfere with correct circuit operation at normal conditions but may cause intermittent or early-life failures. MINVDD testing can detect weak CMOS chips. The minvdd of a chip is the minimum supply voltage value at which a chip can function correctly. It can be used to differentiate between good chips and weak chips. In the first part of this paper, we will study several types of flaws to demonstrate the effectiveness of MINVDD testing. Experimental results show that MINVDD testing is as effective as VLV testing for screening out burn-in rejects. In the second part of this paper, we propose test conditions for low voltage testing, including test voltage, test timing and test sets. Experimental results are presented to validate our proposal.
An analysis of the generalization and maintenance of eye contact taught during play

Purpose: Differential reinforcement and most-to-least prompting were implemented within the context of developmentally appropriate play activities in an effort to improve the eye contact between a 4-year-old boy with pervasive developmental disorder-not otherwise specified (PDD-NOS) and his three therapists. Methods: A multiple baseline design across therapists was used to examine the eye contact of a 4-year-old boy with PDD-NOS. Maintenance data were collected at 1, 2 and 3 months post intervention. Results: The intervention was effective and improvements in eye contact were maintained for at least 3 months post intervention. However, eye contact did not readily generalize across communication partners. Conclusions: Results suggest that eye contact may not generalize to communication partners who are not directly involved in intervention. Results are discussed in terms of implications for practitioners and directions for future research.
Open-trial pilot study of a comprehensive outpatient psychosocial treatment for children with high-functioning autism spectrum disorder

This study examined the feasibility and initial outcomes of a comprehensive outpatient psychosocial treatment (MAXout) for children aged 7–12 years with high-functioning autism spectrum disorder. The 18-week treatment, two 90-minute sessions per week, included instruction and therapeutic activities targeting social/social communication skills, facial emotion recognition, non-literal language skills, and interest expansion. A behavioral system was implemented to reduce autism spectrum disorder symptoms and problem behaviors and increase skills acquisition and maintenance. Feasibility was supported via high levels of treatment fidelity and parent, child, and staff satisfaction. Significant post-treatment improvements were found for the children’s non-literal language skills and facial emotion recognition skills, and parent and staff clinician ratings of targeted social/social communication skills, broad social skills, autism spectrum disorder symptoms, and problem behaviors. Results suggested that MAXout was feasible and may yield positive outcomes for children with high-functioning autism spectrum disorder.
Leadership training to improve adenoma detection rate in screening colonoscopy: a randomised trial

Objective Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared the effect of leadership training versus feedback only on colonoscopy quality in a countrywide randomised trial. Design 40 colonoscopy screening centres with suboptimal performance in the Polish screening programme (centre leader ADR ≤25% during preintervention phase January to December 2011) were randomised to either a Train-Colonoscopy-Leaders (TCLs) programme (assessment, hands-on training, post-training feedback) or feedback only (individual quality measures). Colonoscopies performed June to December 2012 (early postintervention) and January to December 2013 (late postintervention) were used to calculate changes in quality measures. Primary outcome was change in leaders’ ADR. Mixed effect models using ORs and 95% CIs were computed. Results The study included 24 582 colonoscopies performed by 38 leaders and 56 617 colonoscopies performed by 138 endoscopists at the participating centres. The absolute difference between the TCL and feedback groups in mean ADR improvement of leaders was 7.1% and 4.2% in early and late postintervention phases, respectively. The TCL group had larger improvement in ADR in early (OR 1.61; 95% CI 1.29 to 2.01; p<0.001) and late (OR 1.35; 95% CI 1.10 to 1.66; p=0.004) postintervention phases. In the late postintervention phase, the absolute difference between the TCL and feedback groups in mean ADR improvement of entire centres was 3.9% (OR 1.25; 95% CI 1.04 to 1.50; p=0.017). Conclusions Teaching centre leaders in colonoscopy training improved important quality measures in screening colonoscopy. Trial registration number NCT01667198.
New online ecology of adversarial aggregates: ISIS and beyond

Tackling the advance of online threats Online support for adversarial groups such as Islamic State (ISIS) can turn local into global threats and attract new recruits and funding. Johnson et al. analyzed data collected on ISIS-related websites involving 108,086 individual followers between 1 January 1 and 31 August 2015. They developed a statistical model aimed at identifying behavioral patterns among online supporters of ISIS and used this information to predict the onset of major violent events. Sudden escalation in the number of ISIS-supporting ad hoc web groups (“aggregates”) preceded the onset of violence in a way that would not have been detected by looking at social media references to ISIS alone. The model suggests how the development and evolution of such aggregates can be blocked. Science, this issue p. 1459 Online activity of ad hoc extremist groups can be modeled, providing predictive power and potential countermeasures. Support for an extremist entity such as Islamic State (ISIS) somehow manages to survive globally online despite considerable external pressure and may ultimately inspire acts by individuals having no history of extremism, membership in a terrorist faction, or direct links to leadership. Examining longitudinal records of online activity, we uncovered an ecology evolving on a daily time scale that drives online support, and we provide a mathematical theory that describes it. The ecology features self-organized aggregates (ad hoc groups formed via linkage to a Facebook page or analog) that proliferate preceding the onset of recent real-world campaigns and adopt novel adaptive mechanisms to enhance their survival. One of the predictions is that development of large, potentially potent pro-ISIS aggregates can be thwarted by targeting smaller ones.
Literature overview highlights lack of paediatric donation protocols but identifies common themes that could guide their development

Paediatric donation is a unique and extremely sensitive process that requires specific knowledge and competencies. Most countries use protocols for organ and tissue donation to ensure optimal care for the donor and family, but these mainly focus on adults. However, the donation process for children differs from adults in many ways. An overview of the literature was performed to identify protocols for the paediatric population.