Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes

ABSTRACT Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics. IMPORTANCE Coronaviruses are RNA viruses representing a real threat for public health, as evidenced by SARS and the emerging MERS. However, cellular factors required for their replication are poorly understood. Using genome-wide siRNA screening, we identified novel genes supporting infectious bronchitis virus (IBV) replication in human cells. The several host factors identified in this study may provide directions for future research on targeted therapeutics.
Squamous Cell Carcinoma of the External Auditory Meatus (Canal)

A retrospective study of 35 patients with squamous cell carcinoma of the external auditory meatus treated at the Eye and Ear Hospital of the University of Pittsburgh was performed. The standard treatment was a temporal bone resection that corresponded to the extent of the lesion, followed by postoperative radiation therapy. The tumor extensions, symptoms, treatments, survival rates, and prognostic variables were reviewed. Overall, 12 of 35 patients survived. Lesions limited to the external auditory meatus with no erosion had excellent prognoses. Survival in intermediate lesions with bony erosion or middle ear Involvement was related to the status of surgical margins after partial or subtotal temporal bone resections. Extensive lesions that involved the surrounding soft tissue or dura had poor prognoses. The survival value of total temporal bone resection remains unproved.
Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2012: the Influenza Complications Alert Network (FluCAN).

Influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. Immunisation aims to reduce serious morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in Australia. This study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2012 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with influenza confirmed by nucleic acid detection. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 9 April to 31 October 2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities. Influenza A was detected in 83% of patients. Vaccination coverage was calculated from the vaccination status of 1,216 test negative controls and was estimated at 77% in patients 65 years or over and 61% in patients with chronic comorbidities. Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P<0.001). Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. The study results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza during the 2012 season.
Dynamics of whistler spheromaks in magnetized plasmas.

Recent laboratory experiments [Stenzel et al., Phys. Rev. Lett. 96, 095004 (2006)10.1103/PhysRevLett.96. 095004] have demonstrated interesting phenomena of propagating nonlinear whistler structures (spheromaks) and stationary field-reversed configurations, whose magnetic fields exceed the ambient magnetic field strength. Our objective here is to present simulation studies for these nonlinear whistler structures based on the three-dimensional nonlinear electron magnetohydrodynamic equations. The robustness and longevity of the propagating whistler spheromaks found in the experiments are confirmed numerically. Varying the toroidal field of the spheromak in the initial conditions, we find that the polarity and the amplitude of the toroidal field determine the propagation direction and speed of the spheromak. Our simulation results are in excellent agreement with those observed in the laboratory experiments.
Sexual transmission of human T-lymphotropic virus type I (HTLV-I).

STUDY OBJECTIVE To study the seroprevalence of human T-lymphotropic virus type I (HTLV-I) in a sexually active population and to determine sexual behavior risk factors for infection. DESIGN Cross-sectional seroprevalence study using enzyme-linked immunosorbent assay (ELISA) and Western blot. Risk-factor data were gathered by administered questionnaire and chart review. SETTING Two urban, primary care clinics for persons with sexually transmitted diseases run by the Jamaican Ministry of Health. PATIENTS Of the 2050 consecutive patients presenting with new episodes of sexually transmitted disease, 1977 patients were eligible for analysis. MEASUREMENTS AND RESULTS Overall HTLV-I seroprevalence was 5.7%; prevalence increased with age from 1.6% (age, 14 to 19 years) to 5.1% (age, 30 years and older) in men and from 5.3% (age, 14 to 19 years) to 14.1% (age, 30 years and older) in women. Compared with a reference cohort of food service employees, age-adjusted HTLV-I seroprevalence was increased in female patients with sexually transmitted disease (odds ratio = 1.83; CI, 1.41 to 2.83) but not in male patients with sexually transmitted disease. Independent risk factors for HTLV-I infection in women included having had more than ten lifetime sexual partners (odds ratio = 3.52, CI, 1.28 to 9.69) and a current diagnosis of syphilis (odds ratio = 2.12; CI, 1.12 to 3.99). In men, a history of penile sores or ulcers (odds ratio = 2.13; CI, 1.05 to 4.33) and a current diagnosis of syphilis (odds ratio = 3.56; CI, 1.24 to 10.22) were independent risk factors for HTLV-I infection. Of 1977 patients, 5 (0.3%) had antibodies to human immunodeficiency virus type 1 (HIV-1), including 2 with HTLV-I and HIV-1 coinfection. CONCLUSIONS We conclude that HTLV-I is transmitted from infected men to women during sexual intercourse. Our data are consistent with the lower efficiency of female-to-male sexual transmission of HTLV-I, but penile ulcers or concurrent syphilis may increase a man's risk of infection.
Insulin-Like Growth Factor (IGF) 2 Stimulates Steroidogenesis and Mitosis of Bovine Granulosa Cells Through the IGF1 Receptor: Role of Follicle-Stimulating Hormone and IGF2 Receptor1

Abstract Little is known regarding the role of insulin-like growth factor 2 (IGF2) and the regulation of the IGF2 receptor (IGF2R) during follicular development. Granulosa cells were collected from small (1–5 mm) and large (8–22 mm) bovine follicles and were treated with IGF2 for 1–2 days in serum-free medium, and steroid production, cell proliferation, specific 125I-IGF2 binding, and gene expression were quantified. IGF2 increased both estradiol and progesterone production by granulosa cells, and cells from large follicles were more responsive to the effects of IGF2 than those from small follicles. Abundance of aromatase (CYP19A1) mRNA was stimulated by IGF2 and IGF1. The effective dose (ED50) of IGF2 stimulating 50% of the maximal estradiol production was 63 ng/ml for small follicles and 12 ng/ml for large follicles, and these values were not affected by FSH. The ED50 of IGF2 for progesterone production was 20 ng/ml for both small and large follicles. IGF2 also increased proliferation of granulosa cells by 2- to 3-fold, as determined by increased cell numbers and 3H-thymidine incorporation into DNA. Treatment with IGF1R antibodies reduced the stimulatory effect of IGF2 and IGF1 on estradiol production and cell proliferation. Specific receptors for 125I-IGF2 existed in granulosa cells, and 2-day treatment with estradiol, FSH, or cortisol had no significant effect on specific 125I-IGF2 binding. Also, FSH treatment of small- and large-follicle granulosa cells had no effect on IGF2R mRNA levels, whereas IGF1 decreased IGF2R mRNA and specific 125I-IGF2 binding. Granulosa cell IGF2R mRNA abundance was 3-fold greater in small than in large follicles. These findings support the hypothesis that both IGF2 and its receptor may play a role in granulosa cell function during follicular development. In particular, increased free IGF1 in developing follicles may decrease synthesis of IGF2R, thereby allowing for more IGF2 to be bioavailable (free) for induction of steroidogenesis and mitogenesis via the IGF1R.
Current management of middle cerebral artery aneurysms: surgical results with a "clip first" policy.

BACKGROUND One response to randomized trials like the International Subarachnoid Aneurysm Trial has been to adopt a "coil first" policy, whereby all aneurysms be considered for coiling, reserving surgery for unfavorable aneurysms or failed attempts. Surgical results with middle cerebral artery (MCA) aneurysms have been excellent, raising debate about the respective roles of surgical and endovascular therapy. OBJECTIVE To review our experience with MCA aneurysms managed with microsurgery as the treatment of first choice. METHODS Five hundred forty-three patients with 631 MCA aneurysms were managed with a "clip first" policy, with 115 patients (21.2%) referred from the Neurointerventional Radiology service and none referred from the Neurosurgical service for endovascular management. RESULTS Two hundred eighty-two patients (51.9%) had ruptured aneurysms and 261 (48.1%) had unruptured aneurysms. MCA aneurysms were treated with clipping (88.6%), thrombectomy/clip reconstruction (6.2%), and bypass/aneurysm occlusion (3.3%). Complete aneurysm obliteration was achieved with 620 MCA aneurysms (98.3%); 89.7% of patients were improved or unchanged after therapy, with a mortality rate of 5.3% and a permanent morbidity rate of 4.6%. Good outcomes were observed in 92.0% of patients with unruptured and 70.2% with ruptured aneurysms. Worse outcomes were associated with rupture (P = .04), poor grade (P = .001), giant size (P = .03), and hemicraniectomy (P < .001). CONCLUSION At present, surgery should remain the treatment of choice for MCA aneurysms. Surgical morbidity was low, and poor outcomes were due to an inclusive policy that aggressively managed poor-grade patients and complex aneurysms. This experience sets a benchmark that endovascular results should match before considering endovascular therapy an alternative for MCA aneurysms.
Predicting prognosis of rectal cancer patients with total mesorectal excision using molecular markers.

AIM To explore the prognostic variables in rectal cancer patients undergoing curative total mesorectal excision and the effect of postoperative chemotherapy in advanced rectal cancer. METHODS A total of 259 consecutive rectal cancer patients treated with curative total mesorectal excision between 1999 and 2004 were collected. p53, p21, PCNA, and CD44v6 were examined using immunohistochemistry (IHC). The correlation between clinicopathological or molecular variables and clinical outcomes, including local recurrence, metastasis, disease-free survival and overall survival, was analyzed. RESULTS The median follow-up was 44 mo. Five-year survival rates and 5-year disease free survival rates were 75.43% and 70.32%, respectively. Multi-analysis revealed TNM staging, preoperative CEA, and CD44v6 level were independent risk factors predicting overall survival or disease free survival. The hazard ratio of peroperative CEA was 2.65 (95% CI 1.4-5) and 3.10 (95% CI 1.37-6.54) for disease free survival and overall survival, respectively. The hazard ratio of CD44v6 was 1.93 (95% CI 1.04-3.61) and 2.21 (95% CI 1.01-4.88) for disease free survival and overall survival, respectively. TNM staging was the only risk factor predicting local recurrence. Postoperative chemotherapy without radiotherapy did not improve patients' outcome. CONCLUSION TNM staging, preoperative CEA and CD44v6 were independent prognostic factors for rectal cancer patients with total mesorectal excision. Postoperative chemotherapy may be only used together with radiotherapy for rectal cancer patients.
Ebola virus disease: Awareness among dental students in Hungary.

INTRODUCTION The Ebola epidemic has claimed thousands of lives in Africa, and there has been a mounting pressure on the healthcare systems around the globe to prepare for the showing up of patients infected with this virus. Junior clinicians are at the forefront of medical teams, often coming into contact with patients first, during clerking and admissions. This study assesses the level of knowledge of Ebola virus disease (EVD) among dental students at Semmelweis University, Budapest, Hungary. MATERIALS AND METHODS A cross-sectional survey of 257 dental students was carried out across five different courses. Each of the students was asked to fill out a detailed questionnaire comprising of 11 questions, to assess their knowledge about signs and symptoms, investigations, management, and sequelae of the virus and the outbreak. FINDINGS This study highlighted that there is an overall lack of knowledge about critical aspects of EVD among dental students. We found that the participating students scored less than 60% for 8 of the 11 questions, including those assessing their recognition and subsequent management of EVD. CONCLUSION These results are concerning and the medical universities and dental schools need to act fast to prepare the Hungary's dental (and medical) students and junior doctors for an inevitable influx of infected patients.
Enhanced invasiveness of bovine-derived neonatal sequence type 17 group B streptococcus is independent of capsular serotype.

BACKGROUND A defined geographical area (Oxford, United Kingdom) was investigated for the role of group B Streptococcus (GBS) as a human pathogen. METHODS GBS carriage in pregnant women and invasive disease in neonates and adults >60 years of age was studied over a 3-year period. Multilocus sequence typing and capsular serotyping were used to study 369 isolates of GBS from carriage in pregnant women (n=190) and invasive disease in neonates (n=109) and adults >60 years of age (n=70). RESULTS A total of 20.3% of pregnant women carried GBS. Invasive GBS disease occurred at a rate of 0.9 cases per 1000 live births and 11 cases per 100,000 population >60 years of age per annum. Four sequence types (STs) (ST-17, ST-19, ST-23, and ST-1) that were identified with use of multilocus sequence typing accounted for >50% of carried and invasive strains. A single sequence type (ST-17), previously shown to be phylogenetically of bovine origin, was significantly associated with increased invasiveness in neonates (P=.00002), and this was independent of capsular serotype III. In contrast, among adults >60 years of age, no STs exhibited increased invasiveness, compared with STs carried in pregnant women. CONCLUSIONS Enhanced invasiveness associated with ST-17 is specific to neonates and is independent of capsular serotype.
Integration of e-learning resources into a medical school curriculum

Background: E-learning has the potential to make important contributions to medical education, but there has been limited study of a blended approach in which the digital resources are introduced alongside traditional teaching methods such as lectures. Methods: We describe the successful embedding of an e-learning resource into 3 of the 5 weeks of cardiovascular system teaching for 164 first-year medical students by providing scheduled slots in the timetables. A questionnaire completed by the students at the end of the 5 weeks had a response rate of 66%. Students varied in how they made use of the resource, some systematically working through it and others browsing and studying sections felt to be personally most relevant. Results: Almost all (96%) rated the e-learning resources as probably or definitely of value: they particularly valued interactive activities, animations, video demonstrations, video clips of experts and self-assessment exercises. Graduate students had a significantly more favourable assessment of the e-learning resources than their undergraduate colleagues, while female students felt the value in supporting existing learning opportunities more strongly than male students. Conclusions: It should not be assumed that all students will choose to use an e-learning resource in the same way and instructional design should enable alternative approaches. The sequence in which the e-learning resource is used in relation to the other learning opportunities, such as lectures and PBL group discussions, may be important and merits further consideration. The experiences reported in this study provide encouragement and pointers for others engaged in the integration of e-learning in their curriculum.
Regional cerebral, ocular and peripheral vascular effects of naloxone and morphine in unanesthetized rabbits.

Effects of morphine and naloxone were investigated on cerebral, ocular and peripheral blood flow in unanesthetized rabbits. Blood flow measurements were performed with the labelled microsphere method. Cervical sympathotomy was performed on one side the day before the flow determination. Naloxone 2 mg/kg b.w. i.v. had no consistent effect on cerebral, ocular or peripheral blood flow or on mean arterial blood pressure. Morphine 2 mg/kg b.w. i.v. caused a rise in PaCO2 of 0.9 kPa and tended to increase cerebral blood flow in all parts investigated. In the hippocampal region, caudate nucleus and collicles the increase in flow was about 30% which is more than expected from the rise in PaCO2. Blood flow in the retina increased while the other parts of the eye showed no consistent changes in blood flow. Morphine reduced the blood flow in the duodenum by 60%. Mean arterial blood pressure did not change after morphine. No effect of the cervical sympathotomy was detected on cerebral or ocular blood flow before or after morphine or naloxone. Thus, we found no evidence for a tonically operating opioid system controlling cerebral, ocular or peripheral blood flow. However, exogenously administrated opiate can influence blood flows in these areas.
The influence of parents, siblings and peers on pre- and early-teen smoking: a multilevel model.

INTRODUCTION AND AIMS Despite considerable success in tobacco control, many teenagers in Australia and other industrialised countries still smoke tobacco. There is mixed evidence on the relative influence of proximal social networks (parents/siblings/peers) on pre- and early-teen smoking, and no research has examined how these influences compare after accounting for school- and community-level effects.The aim of this study was to compare the relative influences of parents, siblings and peers, after accounting for school- and community-level variation in smoking. DESIGN AND METHODS A cross-sectional fixed and random effects model of smoking prevalence was used, with individuals (n = 7314) nested within schools (n = 231) nested within communities (n = 30). Grade 6 and 8 students (modal ages 11 and 13 years) completed an on-line survey. Key variables included parent/sibling/peer use. Controls included alcohol involvement, sensation seeking, pro-social beliefs, laws/norms about substance use and school commitment. RESULTS There was significant variation in smoking at both the school and community levels, supporting the need for a multilevel model. Individual-level predictors accounted for much of the variance at higher levels. The strongest effects were for number of friends who smoke, sibling smoking and alcohol involvement. Smaller significant effects were found for parent smoking. At the community level, socioeconomic disadvantage was significant, but community-level variance in pro-social and drug-related laws/norms was not related to smoking. DISCUSSION AND CONCLUSIONS Cross-level interactions were generally non-significant. Early teenage smoking was best explained by sibling and peer smoking, and individual risks largely accounted for the substantial variation observed across schools and communities. In terms of future tobacco control, findings point to the utility of targeting families in disadvantaged communities.
Comparison of a single indicator and gravimetric technique for estimation of extravascular lung water in endotoxemic pigs

Objectives:To compare the single thermal indicator dilution (STID) technique for measurement of extravascular lung water (EVLWSTID) with gravimetrically determined EVLW (EVLWGRAV) in anesthetized pigs under sham and endotoxemic conditions. Design:Open experimental comparative animal study. Setting:University animal research laboratory. Subjects:Fifteen anesthetized landrace pigs. Interventions:Endotoxin infusion during 5 hrs in five pigs. Six animals were only anesthetized and rested for 5 hrs. In four additional animals, the impact on EVLWSTID measurements by changes in pulmonary perfusion, ventilation, and the combination of the two was studied. The alterations in ventilation and perfusion were induced by caval balloon inflation, inflation of the pulmonary artery catheter balloon, and bronchial plugging respectively. Measurements and Main Results:The STID technique, with default settings of the intrathoracic blood volume (ITBV) to global end-diastolic volume (GEDV) (i.e., the extrapulmonary intravascular volume between the point of injection of the indicator, and the point of detection) relationship (ITBV = 1.25GEDV), systematically overestimated the EVLW index compared with the gravimetrical method (mean bias of 5.4 mL/kg). By adapting the ITBV to GEDV relationship to the current model (ITBV = 1.52GEDV + 49.7), the accuracy of the STID technique improved. Moreover, the measurement of EVLWSTID proved to be reduced by manipulation of pulmonary perfusion and ventilation. However, the STID technique could detect an increase in EVLW during endotoxemia independent of the ITBV/GEDV relationship used. Conclusion:Despite technological improvement, the dilution techniques for the measurement of EVLW might still be influenced by changes in perfusion and ventilation. The STID technique, in addition, might demand adjustment of the ITBV/GEDV relationship to the particular condition and species subjected to measurement. The STID technique may, however, be a useful tool for monitoring changes of EVLW over time, but further studies are warranted to confirm this.