Miracle-dz/UniFAR-FTUs huggingface dataset:
Necl‐5/PVR enhances PDGF‐induced attraction of growing microtubules to the plasma membrane of the leading edge of moving NIH3T3 cells

Microtubules (MTs) search for and grow toward the leading edge of moving cells, followed by their stabilization at a specific structure at the rear site of the leading edge. This dynamic re‐orientation of MTs is critical to directional cell movement. We previously showed that Necl‐5/poliovirus receptor (PVR) interacts with platelet‐derived growth factor (PDGF) receptor and integrin αvβ3 at the leading edge of moving NIH3T3 cells, resulting in an enhancement of their directional movement. We studied here the role of Necl‐5 in the PDGF‐induced attraction of growing MTs to the leading edge of NIH3T3 cells. Necl‐5 enhanced the PDGF‐induced growth of MTs and attracted them near to the plasma membrane of the leading edge of NIH3T3 cells in an integrin αvβ3‐dependent manner. Furthermore, Necl‐5 enhanced the PDGF‐induced attraction of the plus‐end‐tracking proteins (+TIPs), including EB1, CLIP170, an intermediate chain subunit of cytoplasmic dynein, and p150Glued, a subunit of dynactin, near to the plasma membrane of the leading edge. Thus, Necl‐5 plays a role in the attraction of growing MTs to the plasma membrane of the leading edge of moving cells.
The thymic medulla: a unique microenvironment for intercellular self-antigen transfer

Central tolerance is shaped by the array of self-antigens expressed and presented by various types of thymic antigen-presenting cells (APCs). Depending on the overall signal quality and/or quantity delivered in these interactions, self-reactive thymocytes either apoptose or commit to the T regulatory cell lineage. The cellular and molecular complexity underlying these events has only recently been appreciated. We analyzed the ex vivo presentation of ubiquitous or tissue-restricted self-antigens by medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs), the two major APC types present in the medulla. We found that the ubiquitously expressed nuclear neo–self-antigen ovalbumin (OVA) was efficiently presented via major histocompatibility complex class II by mTECs and thymic DCs. However, presentation by DCs was highly dependent on antigen expression by TECs, and hemopoietic cells did not substitute for this antigen source. Accordingly, efficient deletion of OVA-specific T cells correlated with OVA expression by TECs. Notably, OVA was only presented by thymic but not peripheral DCs. We further demonstrate that thymic DCs are constitutively provided in situ with cytosolic as well as membrane-bound mTEC-derived proteins. The subset of DCs displaying transferred proteins was enriched in activated DCs, with these cells being most efficient in presenting TEC-derived antigens. These data provide evidence for a unique, constitutive, and unidirectional transfer of self-antigens within the thymic microenvironment, thus broadening the cellular base for tolerance induction toward promiscuously expressed tissue antigens.
Lessons Learned from Designing a Programming System to Support Middle School Girls Creating Animated Stories

Traditional approaches to teaching computer science are often unsuccessful in attracting girls into the discipline. Our hypothesis is that presenting computer programming as a means to the end of storytelling will help motivate girls to learn to program, a traditional gateway to computer science. In this paper, we present a case study in designing a version of the Alice programming system to support storytelling. We present lessons we learned about what supports are necessary to enable girls to program animated movies and describe the kinds of programming tasks that arise in girls' stories
Hepatitis C virus treatment as prevention in people who inject drugs: testing the evidence

Purpose of review The majority of hepatitis C virus (HCV) infections in the United Kingdom and many developing countries were acquired through injecting. New clinical guidance suggests that HCV treatment should be offered to people with a transmission risk – such as people who inject drugs (PWID) – irrespective of severity of liver disease. We consider the strength of the evidence base and potential problems in evaluating HCV treatment as prevention among PWID. Recent findings There is good theoretical evidence from dynamic models that HCV treatment for PWID could reduce HCV chronic prevalence and incidence among PWID. Economic evaluations from high-income settings have suggested HCV treatment for PWID is cost-effective, and that in many settings HCV treatment of PWID could be more cost-effective than treating those at an equivalent stage with no ongoing transmission risk. Epidemiological studies of older interferon treatments have suggested that PWID can achieve similar treatment outcomes to other patient groups treated for chronic HCV. Impact and cost-effectiveness of HCV treatment is driven by the potential ‘prevention benefit’ of treating PWID. Model projections suggest that more future infections, end stage liver disease, and HCV-related deaths will be averted than lost through reinfection of PWID treated successfully for HCV. However, there is to date no empirical evidence from trials or observational studies that test the model projections and ‘prevention benefit’ hypothesis. In part this is because of uncertainty in the evidence base but also there is unlikely to have been a change in HCV prevalence due to HCV treatment because PWID HCV treatment rates historically in most sites have been low, and any scale-up and switch to the new direct acting antiviral has not yet occurred. There are a number of key uncertainties in the data available on PWID that need to be improved and addressed to evaluate treatment as prevention. These include estimates of the prevalence of PWID, measurements of HCV chronic prevalence and incidence among PWID, and how to interpret reinfection rates as potential outcome measures. Summary Eliminating HCV through scaling up treatment is a theoretical possibility. But empirical data are required to demonstrate that HCV treatment can reduce HCV transmission, which will require an improved evidence base and analytic framework for measuring PWID and HCV prevalence.
Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients.

BACKGROUND: Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome. The octapeptide lanreotide is available in slow release form, which could eliminate the necessity of twice a day injections as with octreotide. PATIENTS AND METHODS: 39 patients with carcinoid syndrome were included in a prospective multicentre study. Patients received lanreotide 30 mg intramuscularly every 14 days for six months. The number and intensity of flushing episodes and bowel movements, urinary 5 hydroxy-indolacetic acid (5 HIAA) concentrations, and variations of tumour mass were recorded. RESULTS: After one month of treatment, flushing episodes (median (range)) decreased significantly (3 (0.3-24) episodes per day v 1 (0-15), p = 0.04) and completely resolved in 39% of the patients. A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea. Urinary 5 HIAA concentrations were unchanged in 57% of the patients and decreased in 18%. After six months of treatment, the actuarial proportions of patients with at least a 50% decrease in the number of flushing episodes and bowel movements were 54% and 56%, respectively. Forty two per cent of the patients who were treated for six months had at least a 50% reduction in 5 HIAA values. No clear signs of regression of tumours were seen in any of the patients. Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25% of the patients. Biliary lithiasis appeared in two patients after six months of lanreotide. CONCLUSION: Lanreotide, 30 mg intramuscularly every other week, is an effective and convenient treatment in patients with the carcinoid syndrome.
Changing Health Behaviour: Intervention and Research with Social Cognition Models

Notes on Contributors Acknowledgements List of abbreviations Introduction social cognition models and changing health behaviours Encouraging safer-sex behaviours development of the SHARE sex education programme Smoking and smoking cessation modifying perceptions of risk Reducing the risks of exposure to radon gas an application of the Precaution Adoption Process Model Reducing fat intake interventions based on the Theory of Planned Behaviour Increasing participation with colorectal cancer screening the development of a psycho-educational intervention Changing health behaviours the role of implementation intentions Changing drivers' attitudes to speeding using the Theory of Planned Behaviour Improving pedestrian road safety among adolescents an application of the Theory of Planned Behaviour Increasing cycle helmet use in school-age cyclists an intervention based on the Theory of Planned Behaviour Conclusion using social cognition models to develop health behaviour interventions: problems and assumptions Index
Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that metabolic risk markers arise when vulnerable individuals are exposed to social challenges later in life.
UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

This work presents evidence that photo-excitation of guanine radical cations results in high yields of deoxyribose sugar radicals in DNA, guanine deoxyribonucleosides and deoxyribonucleotides. In dsDNA at low temperatures, formation of C1′• is observed from photo-excitation of G•+ in the 310–480 nm range with no C1′• formation observed ≥520 nm. Illumination of guanine radical cations in 2′dG, 3′-dGMP and 5′-dGMP in aqueous LiCl glasses at 143 K is found to result in remarkably high yields (∼85–95%) of sugar radicals, namely C1′•, C3′• and C5′•. The amount of each of the sugar radicals formed varies dramatically with compound structure and temperature of illumination. Radical assignments were confirmed using selective deuteration at C5′ or C3′ in 2′-dG and at C8 in all the guanine nucleosides/tides. Studies of the effect of temperature, pH, and wavelength of excitation provide important information about the mechanism of formation of these sugar radicals. Time-dependent density functional theory calculations verify that specific excited states in G•+ show considerable hole delocalization into the sugar structure, in accord with our proposed mechanism of action, namely deprotonation from the sugar moiety of the excited molecular radical cation.
The Use of Fast and Thermal Neutron Detectors Based on Oxide Scintillators in Inspection Systems for Prevention of Illegal Transportation of Radioactive Substances

We present results of our studies on the practical application of an efficient method for detection of fast and thermal neutrons using the process of inelastic scattering on nuclei present in inorganic scintillators. The most obvious field of practical application for this method is inspection systems for the prevention of illegal transportation of radioactive substances. Especially promising is the design of a small-sized neutron detector for portable radioactive material detection systems using “scintillator-avalanche photodiode” assemblies.
Should First-line Empiric Treatment Strategies for Neonates Cover Coagulase-negative Staphylococcal Infections in Kenya?

Background: Neonatal mortality remains high in sub-Saharan Africa, and a third of deaths are estimated to result from infection. While coagulase-negative staphylococci (CoNS) are leading neonatal pathogens in resource-rich settings, their role, and the need for early anti-Staphylococcal treatment in empiric antibiotic guidelines, is unknown in sub-Saharan Africa. Methods: We examined systematic clinical and microbiologic surveillance data from all neonatal admissions to Kilifi County Hospital (1998–2013) to determine associated case fatality and/or prolonged duration of admission associated with CoNS in neonates treated according to standard World Health Organization guidelines. Results: CoNS was isolated from blood culture in 995 of 9552 (10%) neonates. Case fatality among neonates with CoNS isolated from blood did not differ from other neonatal admissions (P = 0.2), and duration of admission was not prolonged [odds ratio (OR) = 0.9 (0.7–1.0), P = 0.040]. Neonates with CoNS were more likely to have convulsions [OR = 1.4 (1.0–1.8), P = 0.031] but less likely to have impaired consciousness or severe indrawing [OR = 0.8 (0.7–0.9), P = 0.025; OR = 0.9 (0.7–1.0), P = 0.065]. Conclusions: CoNS isolation in blood cultures at admission was not associated with adverse clinical outcomes in neonates treated according to standard World Health Organization guidelines for hospital care in this setting. There is no evidence that first-line antimicrobial treatment guidelines should be altered to increase cover for CoNS infections in neonates in this setting.
Nonlocalized lower gastrointestinal bleeding: provocative bleeding studies with intraarterial tPA, heparin, and tolazoline.

PURPOSE The purpose of this study was to assess the efficacy and safety of provocative mesenteric angiography with tissue plasminogen activator (tPA), heparin, and tolazoline in patients with nonlocalized lower gastrointestinal (LGI) bleeding. Results were examined to assess the clinical impact of the study on patients who had positive or negative results from elective provocative bleeding studies. MATERIALS AND METHODS Seventeen provocative bleeding studies for occult LGI bleeding were performed in 16 patients, nine of whom were women, aged 44-79 years. All patients had negative results from previous endoscopic and angiographic studies. Patients' requirements for blood transfusion ranged from 6 to 69 units. Studies were performed electively. Blood group matching and cross-matching were performed for all patients. To provoke bleeding, a combination of intravenous heparin, intraarterial tolazoline, and intraarterial tPA was used. Doses used included 3,000-10,000 U heparin, 25-100 mg intraarterial tolazoline, and 10-50 mg intraarterial tPA (mean, 20.3 mg). Duration of follow-up was 3-34 months. RESULTS Seventeen elective provocative studies were performed in 16 patients with occult LGI bleeding, leading to provoked bleeding in six patients (37.5%). In addition, two previously undiagnosed vascular abnormalities were diagnosed, which did not bleed during provocation. Therefore, an abnormality was identified in eight of 16 patients (50%) overall. There were no procedural complications encountered during or after any of the 17 procedures. In six patients in whom bleeding was successfully provoked, four bleeding episodes occurred in the large bowel and two occurred in the small bowel. Five of the positively provoked patients had a previously positive tagged red cell scintigraphic study. Three patients had superselective embolization at the time of provoked bleeding. Two were treated with estrogen therapy, and one patient was treated palliatively. Five of these six patients required no further therapy for LGI bleeding. Ten patients (including two with vascular abnormalities) did not bleed during the provoked study with tPA. Follow-up of the group of eight patients with completely normal study results ranged from 3 to 34 months in duration, and during the follow-up period, five patients experienced repeated bleeding and one had no further bleeding. One patient was diagnosed with an ileal vascular lesion during subsequent intraoperative enteroscopy and underwent surgical resection. One patient was lost to follow-up. CONCLUSION Intraarterial provocative mesenteric angiography with heparin, vasodilator, and tPA identified the site of bleeding in 37.5% of patients in our study group and contributed to treatment in 50%. This small study indicates that the procedure appears to be safe, with no complications encountered in this series. Larger prospective studies are needed to fully assess the safety and efficacy of the technique and to optimize the pharmacologic protocol and patient selection.
Beauty, binaries, and the big screen in China: character gender in feature films

This study examines gender constructions of the main characters in Chinese top-grossing feature films, 2002–2011, and the sex of content creators in relation to film content. Content analysis of 332 characters reveals that women are more likely than men to be young, sexualized, and conform to an ideal image. Male characters are older and reflect traditional Chinese norms of masculinity. Women are rarely present among content creators and are most likely to be writers or producers. Findings indicate that Chinese film content reflects the growing Chinese beauty economy.
Health Professionals’ Explanations of Suicidal Behaviour: Effects of Professional Group, Theoretical Intervention Model, and Patient Suicide Experience

In a help relation with a suicidal person, the theoretical models of suicidality can be essential to guide the health professional’s comprehension of the client/patient. The objectives of this study were to identify health professionals’ explanations of suicidal behaviors and to study the effects of professional group, theoretical intervention models, and patient suicide experience in professionals’ representations. Two hundred and forty-two health professionals filled out a self-report questionnaire. Exploratory principal components analysis was used. Five explanatory models were identified: psychological suffering, affective cognitive, sociocommunicational, adverse life events, and psychopathological. Results indicated that the psychological suffering and psychopathological models were the most valued by the professionals, while the sociocommunicational was seen as the least likely to explain suicidal behavior. Differences between professional groups were found. We concluded that training and reflection on theoretical models in general and in communicative issues in particular are needed in the education of health professionals.
Multi-institution case–control and cohort study of risk factors for the development and mortality of Clostridium difficile infections in Japan

Objective To examine risk factors for Clostridium difficile infection (CDI) morbidity and mortality in Japan. Design Multimethod investigation including a case–control study and cohort study. Setting 47 participating facilities of the National Hospital Organization (NHO). Participants 1026 patients with CDI and 878 patients in the control group over the age of 18 years admitted to the subject NHO facilities from November 2010 to October 2011. Main outcome measures In a case–control study, we identify risk factors for CDI development. Next, in a cohort study, we identify risk factors for all-cause mortality within 30 days following CDI onset. Results A total of 1026 cases of CDI meeting the definitions of this investigation were identified, encompassing 878 patients at 42 of the 47 subject facilities. In the case–control study, we identified, compared with no antibiotics use, use of first-generation and second-generation cephem antibiotics (OR 1.44; 95% CI 1.10 to 1.87), use of third-generation and fourth-generation cephem antibiotics (OR 1.86; 95% CI 1.48 to 2.33) and use of carbapenem antibiotics (OR 1.87; 95% CI 1.44 to 2.42) the risk factors for CDI development. However, use of penicillin was not identified as a risk factor. In the cohort study, sufficient data for analysis was available for 924 CDI cases; 102 of them (11.0%) resulted in death within 30 days of CDI onset. Compared with no anti-CDI drug use, use of vancomycin was associated with reduced risk of mortality (OR 0.43; 95% CI 0.25 to 0.75) whereas metronidazole was not. Conclusions The findings mirror those of previous studies from Europe and North America, identifying the administration of broad-spectrum antibiotics as a risk factor for CDI development. The use of vancomycin is associated with a decreased risk of mortality.