Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms for Glycolipid Antigen-Driven Cytokine Polarization by Vα14i NKT Cells

Certain glycolipid Ags for Vα14i NKT cells can direct the overall cytokine balance of the immune response. Th2-biasing OCH has a lower TCR avidity than the most potent agonist known, α-galactosylceramide. Although the CD1d-exposed portions of OCH and α-galactosylceramide are identical, structural analysis indicates that there are subtle CD1d conformational differences due to differences in the buried lipid portion of these two Ags, likely accounting for the difference in antigenic potency. Th1-biasing C-glycoside/CD1d has even weaker TCR interactions than OCH/CD1d. Despite this, C-glycoside caused a greater downstream activation of NK cells to produce IFN-γ, accounting for its promotion of Th1 responses. We found that this difference correlated with the finding that C-glycoside/CD1d complexes survive much longer in vivo. Therefore, we suggest that the pharmacokinetic properties of glycolipids are a major determinant of cytokine skewing, suggesting a pathway for designing therapeutic glycolipids for modulating invariant NKT cell responses.
Conditional protein phosphorylation regulates BK channel activity in rat cerebellar Purkinje neurons

Large conductance calcium‐ and voltage‐activated potassium (BK) channels are widely expressed in the mammalian central nervous system. Although the activity of BK channels in endocrine and vascular cells is regulated by protein kinases and phosphatases associated with the channel complex, direct evidence for such modulation in neurons is largely lacking. Single‐channel analysis from inside‐out patches isolated from the soma of dissociated rat cerebellar Purkinje neurons demonstrated that the activity of BK channels is regulated by multiple endogenous protein kinases and protein phosphatases in the membrane patch. The majority of BK channels were non‐inactivating and displayed a ‘low’ activity phenotype determined at +40 mV and 1 μM intracellular free calcium. These channels were activated by cAMP‐dependent protein kinase (PKA) associated with the patch and the extent of PKA activation was limited by an opposing endogenous type 2A‐like protein phosphatase (PP2A). Importantly, PKA activation was dependent upon the prior phosphorylation status of the BK channel complex dynamically controlled by protein kinase C (PKC) and protein phosphatase 1 (PP1). In contrast, Purkinje cells also displayed a low proportion of non‐inactivating BK channels with a ‘high’ activity under the same recording conditions and these channels were inhibited by endogenous PKA. Our data suggest that: (1) multiple endogenous protein kinases and phosphatases functionally couple to the BK channel complex to allow conditional modulation of BK channel activity in neurons, and (2) native, phenotypically distinct, neuronal BK channels are differentially sensitive to PKA‐dependent phosphorylation.
Targeting of Somatic Hypermutation by Enhancer and Enhancer-Like Sequences

Somatic hypermutation (SH) generates point mutations within rearranged immunoglobulin (Ig) genes of activated B cells, providing genetic diversity for the affinity maturation of antibodies. SH requires the activation-induced cytidine deaminase (AID) protein and transcription of the mutation target sequence, but how the Ig gene specificity of mutations is achieved has remained elusive. We show here using a sensitive and carefully controlled assay that the Ig enhancers strongly activate SH in neighboring genes even though their stimulation of transcription is negligible. Mutations in certain E-box, NFkB, MEF2, or Ets family binding sites—known to be important for the transcriptional role of Ig enhancers—impair or abolish the activity. Full activation of SH typically requires a combination of multiple Ig enhancer and enhancer-like elements. The mechanism is evolutionarily conserved, as mammalian Ig lambda and Ig heavy chain intron enhancers efficiently stimulate hypermutation in chicken cells. Our results demonstrate a novel regulatory function for Ig enhancers, indicating that they either recruit AID or alter the accessibility of the nearby transcription units. Citation: Buerstedde J-M, Alinikula J, Arakawa H, McDonald JJ, Schatz DG (2014) Targeting of Somatic Hypermutation by mmunoglobulin Enhancer and Enhancer-Like Sequences. PLoS Biol 12(4): e1001831. doi:10.1371/journal.pbio. 1001831 Academic Editor: David Nemazee, Scripps Research Institute, United States of America Received November 11, 2013; Accepted February 21, 2014; Published April 1, 2014 Copyright: 2014 Buerstedde et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: J-M.B. was supported by an International Outgoing Marie Curie Fellowship. J.J.M. was supported in part by NIH T32 AI07019. D.G. S is an investigator of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: GCV, immunoglobulin gene conversion; SH, somatic hypermutation. * E-mail: brstdd@gmail.com (J-MB); david.schatz@yale.edu (DGS)
Lymph Node Count at Inguinofemoral Lymphadenectomy and Groin Recurrences in Vulvar Cancer

Objective The objective of the study is to determine the risk factors for groin recurrence (GR) in patients with primary vulvar squamous cell carcinoma (SCC) after inguinofemoral lymphadenectomy (IFL) without lymph node metastases and/or adjuvant chemoradiotherapy. Methods The study is a multicenter retrospective review of clinical and histopathological data of patients with lymph node–negative vulvar SCC who underwent an IFL. Patients with and without GRs were compared to identify risk factors. Results In 134 patients, 252 groins were eligible for the analyses—16 patients underwent ipsilateral IFL and 118 patients underwent bilateral IFL. Groin recurrences occurred in 4 (1.6%) of the 252 dissected groins. Besides, 1 patient who underwent ipsilateral IFL had a recurrence in the nonoperated contralateral groin; this groin was left out of analysis. The median number of dissected nodes per groin was 9.8 (range, 1–38) in all patients and 6.5 (range, 5–8) in patients with GR. Multivariate analyses showed that GR was related to poor differentiation (P = 0.04), and node count less than 9 (P = 0.04), no association with age, tumor localization, tumor diameter, focality, invasion depth, or stage was found. Nineteen patients with both low node count and poor differentiation had 19% GRs. Survival analyses showed less favorable survival in patients with poor differentiation. Conclusions The overall risk of developing GR after negative IFL in patients with vulvar SCC is low (1.6% per groin) but significantly higher in patients with tumors with a poor differentiation and lymph node count less than 9 at IFL. A large well-designed prospective study is needed to evaluate closer surveillance in patients at risk.
A Dynamic Ticket Pricing Approach for Soccer Games

This study proposes a mathematical model of dynamic pricing for soccer game tickets. The logic behind the dynamic ticket pricing model is price change based on multipliers which reflect the effects of time and inventory. Functions are formed for the time and inventory multipliers. The optimization algorithm attempts to find optimal values of these multipliers in order to maximize revenue. By multiplying the mean season ticket price (used as the reference price) by the multipliers, dynamic ticket prices are obtained. Demand rates at different prices are needed for the model, and they are provided by a unique fuzzy logic model. The results of this model are compared with real data to test the model’s effectiveness. According to the results of the dynamic pricing model, the total revenue generated is increased by 8.95% and 0.76% compared with the static pricing strategy in the first and second cases, respectively. The results of the fuzzy logic model are also found to be competitive and effective. This is the first time a fuzzy logic model has been designed to forecast the attendance of soccer games. It is also the first time this type of mathematical model of dynamic pricing for soccer game tickets has been designed.
Antibiotic Resistance and Usage-A Survey on the Knowledge, Attitude, Perceptions and Practices among the Medical Students of a Southern Indian Teaching Hospital.

BACKGROUND Examining the knowledge, attitude, perceptions and practices (KAP) of the medical students regarding antibiotic resistance (ABR) and use can help us in devising suitable educational interventions for them, tailored according to their earlier held knowledge, beliefs, capabilities and experience. METHODS A cross sectional, questionnaire based survey was conducted among the second year medical students of a teaching hospital, whereby their KAP regarding antibiotic use and resistance was assessed by using a five point Likert scale, whose responses ranged from 'strongly agree' to 'strongly disagree,' 'always' to 'never and 'very important' to 'unimportant'. The data was analyzed by using simple descriptive statistics. Wherever it was relevant, the Chi-square test was used to determine any significant difference. RESULTS The response rate was 100 per cent. The number of respondents who agreed that ABR was an important and a serious public health issue in our teaching hospital (n= 66, 68 per cent), was significantly less (p < 0.001) as compared to the number of respondents who agreed that ABR was an important and a serious issue which the country (n = 86, 88.65 per cent) and the world (n = 88, 90.7 per cent) were facing. Only 77.3 per cent (n= 75) of the respondents were aware that bacteria were not responsible for causing colds and flu, while the remaining 22.7 per cent (n = 22) were not knowledgeable about this fact. More than 80 per cent rated the adverse effect profile of the antibiotic and the risk of a superinfection as the important factors which deserved consideration. Cost of the antibiotic was considered to be an important factor deserving consideration by only 56.7 percent (n=55) of the participants. CONCLUSIONS Our survey revealed that most of the students were aware of the antimicrobial resistance and its consequences. The only concern was their casual attitude regarding the antibiotic use. Further educational interventions are necessary to improve their understanding and perceptions on antibiotic resistance, as well as their attitude towards antibiotic use.
Cancer risk in patients with earlier diagnosis of cutaneous melanoma In situ

We calculated the short‐term and long‐term risks of developing cancer among 3,766 patients with a diagnosis of cutaneous melanoma in situ in Sweden from 1958 to 1992. In total, 393 patients developed a primary cancer at any site compared with an expected number of 177 [standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) = 2.0–2.4]. Patients below 60 years of age at diagnosis had the highest SIR (2.7, 95% CI = 2.3–3.2). The overall risks were similar between men and women. The highest risk was seen during the first year of follow‐up, though the risk remained elevated also after 15 or more years of follow‐up. For specific sites, the highest SIR was found for developing invasive cutaneous malignant melanoma (SIR = 22.2). The risk of subsequent primary non‐melanoma skin cancer was elevated 8‐fold in men and almost 7‐fold in women. An elevated risk was also found for female breast cancer (SIR = 1.4). Especially among women, other sites with increased cancer risk (though not significant) were non‐Hodgkin's lymphoma (SIR = 1.9), multiple myeloma (3.2) and cancers of the colon (1.6) and pancreas (1.6). In conclusion, patients with melanoma in situ run a generally increased risk of developing primary cancers, especially cutaneous malignant melanoma and non‐melanoma skin cancer. The increased long‐term risk of cancer after diagnosis of melanoma in situ may be due to continuing carcinogenic exposure or to intrinsic tumor susceptibility. Int. J. Cancer 83:314–317, 1999. © 1999 Wiley‐Liss, Inc.
Comparison of AFB Smear Microscopy and Culture from Specimens Received for the Diagnosis of Extra Pulmonary Tuberculosis

Objectives: This study was undertaken to see the role of AFB microscopy and culture for the diagnosis of extra pulmonary tuberculosis. Design and Setting: This descriptive study was carried out at PMRC TB Research Centre King Edward Medical University/Mayo Hospital Lahore. Subject and Methods: Symptomatic suspects of extra-pulmonary TB were asked to submit their respective samples for AFB smear and culture. Smears were prepared and stained by Zheil Neelsen method and were subjected to culture on Lowenstein Jensen media. Results: The smear and culture results of 260 extra-pulmonary specimens were analyzed. Smear positivity was seen only in 3.85%, and the culture on Lowenstein Jensen media showed positivity of 18.45 %. Microscopy when compared with culture showed sensitivity of 20.84% and specificity 100%, positive predictive value 100%, negative predictive value of 84% with false positive rate of 0 and false negative rate of 79.17%. Conclusion: Smear microscopy is not found to be a sensitive tool, giving a high false negative rate when compared with culture. Thus culture is reliable and gold standard for bacteriological diagnosis of extra pulmonary tuberculosis.
Properties of the Picker Patient Experience questionnaire in a randomized controlled trial of long versus short form survey instruments.

BACKGROUND The purpose of this study was to compare the performance of the 15-item Picker Patient Experience questionnaire (PPE-15) when embedded in a short form instrument as compared with a longer form measure. METHODS A postal questionnaire survey of patients recently discharged from two hospital trusts was carried out. Patients were randomized to receive the PPE-15 in either a four-page or a 12-page survey instrument. RESULTS A total of 1445 questionnaires were mailed to patients in either four- or 12-page formats. A total of 949 (65.67 per cent) forms were returned. No difference in response rate was found between the two versions of the questionnaire. Item completion and psychometric properties of the PPE-15 were not found to differ significantly between the two arms of the trial. CONCLUSION In this survey the length of questionnaire in which the PPE-15 was embedded had no impact in terms of response rate or data quality. Consequently, the results suggest that length of questionnaire, up to the 108 items included in the 12-page survey, is unlikely to adversely affect results on the PPE-15.
Changes in biliary lipid secretion during normal development and diurnal cycling in the rat.

Biliary lipid secretion in conjunction with hepatic cholesterol synthesis was determined in normal male rats at 4, 5, 7, and 9 weeks of age, during a period of linear growth and a near fourfold increase in liver size. Studies were performed both at periods of low (mid-light cycle) and high (mid-dark cycle) hepatic cholesterol synthesis. Biliary bile salt, phospholipid, and cholesterol secretion (per g of liver) markedly decreased with an increase in liver size. Whereas the secretion of bile salts and phospholipid was not significantly different in mid-dark and mid-light periods for animals of the same age, cholesterol secretion was greater in the mid-dark than in the mid-light period at 5, 7, and 9 weeks of age. Relationships between biliary cholesterol secretion and bile salt and phospholipid secretion differed at mid-dark and mid-light periods, as follows: cholesterol secretion was not significantly related to bile salt secretion at mid-dark (r = 0.49, P > 0.05) but was related at mid-light (r = 0.73, P = 0.003); and although cholesterol secretion was significantly related to phospholipid secretion at mid-dark, this relationship was not nearly as strong as at mid-light (P < 0.005, comparing r = 0.95 at mid-light with r = 0.53 at mid-dark). In contrast, at mid-dark, biliary cholesterol secretion was strongly related to hepatic cholesterol synthesis (r = 0.84, P < 0.0001) whereas at mid-light the two were not significantly related (r = 0.13, P > 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Frequency of musculoskeletal injuries and risk factors associated with injuries incurred in Quarter Horses during races.

OBJECTIVE To determine the frequency and anatomic location of musculoskeletal injuries incurred by Quarter Horses during races and to compare data from injured horses and matched control horses. DESIGN Matched case-control study. ANIMALS 97 Quarter Horses that sustained a musculoskeletal injury during races and 291 horses from the same races that were not injured. PROCEDURE Data examined included racing history, race-entrant characteristics, racing events determined by analysis of videotapes of races, and, when performed, results of prerace physical inspections. Data for injured horses were compared with data for control horses, using conditional logistic regression. RESULTS Incidence of a catastrophic injury among Quarter Horses during races was approximately 0.8/1,000 race starts, whereas incidence of musculoskeletal injury during racing was approximately 2.2/1,000 race starts. Odds of musculoskeletal injury were approximately 8 times greater among horses assessed to be at increased risk of injury on the basis of results of prerace physical inspection than for horses not considered to be at increased risk of injury. Evidence was lacking that 2-year-old horses were at increased risk of injury or that sex influenced the risk of injury among Quarter Horses during races. CONCLUSIONS AND CLINICAL RELEVANCE Incidence of racing injury among Quarter Horses appears to be lower than that observed among Thoroughbreds. Regulatory veterinarians can identify horses at increased risk of injury on the basis of prerace physical inspection, indicating that these inspections could be used to reduce the risk of injury during races.
Communicating the Benefits of Chronic Preventive Therapy

Patients' informed acceptance of chronic medical therapy hinges on communicating the potential benefits of drugs in quantitative terms. In a hypothetical scenario of treatment initiation, the authors assessed how three different formats of the same data affected the willingness of 100 outpatients to take what were implied to be three different lipid-lowering drugs. Side-effects were declared negligible and costs insured. Subjects make a "yes-no" decision about taking such a medication, and graded the decision on a certainty scale. Advised of a relative risk reduction-"34% reduction in heart attacks"-88% of the patients assented to therapy. All other formats elicited significantly more refusals (p < 0.0001): for absolute risk difference—"1.4% fewer patients had heart attacks"—42% assented; for in verted absolute risk—"treat 71 persons for 5 years to prevent one heart attack"—only 31% accepted treatment. When the data were extrapolated to disease-free survival—"average gain of 15 weeks"—40% consented. Similar responses were obtained for descriptions of an antihypertensive drug: 89% assented to therapy when given relative risk reduction but only 46% when given absolute risk reduction. The subjects were confident in both acceptance and refusal: 93% of the decisions were rated "somewhat certain" to "completely certain. " The authors conclude that patients' views of medical therapy are shaped by the formats in which potential benefits are presented. Multiple complementary formats may be most ap propriate. The results imply that many patients may decline treatment if briefed on the likelihood or extent of benefit. Key words: patient compliance; framing effects; informed consent; physician-patient communication. (Med Decis Making 1995;15:152-157)
Frozen electron solid in the presence of small concentrations of defects.

We investigate the freezing of a low-density electron liquid for a two-dimensional electron layer in the presence of low levels of defects typical of a high-quality semiconductor interface. We use a memory function approach with mode-coupling approximation and include the effect of strong electron-electron correlations, which we find are crucial for the transition. For a range of low impurity concentrations we find a stable frozen solid with a liquidlike short-range order. At higher impurity concentrations the electrons localize separately and there is no short-range order. Our electron-density vs peak-mobility phase diagram at zero temperature is in agreement with recent metal-insulator transition experiments in silicon heterostructures. \textcopyright{} 1996 The American Physical Society.
New emerging correlates of weight satisfaction in women: husband -related factors and caffeine intake

Ba ckground : Weight satisfaction is an important determinant of weight-related behaviors and may result in overweight, obesity or eating disorders. To assess weight satisfaction and its related factors, including dietary intake and spouse- related factors, in adult women. M ethods : This is a descriptive-analytic cross-sectional study carried out in North of Iran. Through random sampling, 450 women aged 22-55 years under coverage of health centers were recruited from May 2012 to February 2013. Data were collected by face to face interviewing the individuals. Participants’ height, and weight and waist circumferences were recorded. Body mass index (BMI) was calculated. We used the 24-hour recall questionnaire to estimate food intake in two days of the week. Weight satisfaction was evaluated through questioning. Multivariate logistic regression was used to determine the major factors related to weight satisfaction. Results : Weight satisfaction was 62.4% among women. About 70% of women were overweight or obese (BMI≥ 25 kg/m2). The odds of weight dissatisfaction were higher in younger, healthy individuals and those who take more caffeine on a daily basis. Moreover, the odds of weight dissatisfaction were lower in underweight/normal weight (BMI< 25 kg/m2) women and the overweight women. In addition, the rate of dissatisfaction was significantly higher in women who believed their husbands are dissatisfied about their weight and women whose husbands were in fact dissatisfied about their weight. Conclusion : Weight satisfaction was prevalent in participants and related to age, disease status, caffeine intake, BMI and husband-related factors.
Prevention of Invasive Meningococcal Disease in the United States: Current State of the Art

Neisseria meningitidis causes potentially fatal and often debilitating invasive meningococcal disease (IMD). IMD remains a serious health problem for healthcare providers and public health officials despite approximately 80% of US IMD being vaccine-preventable. In 2005, the Advisory Committee on Immunization Practices (ACIP) recommended routine immunization of adolescents aged 11-12 years and, in 2007, this recommendation was expanded to include all adolescents aged 11-18 years. Adolescent disease burden has since declined. For new vaccination strategies to improve beyond standard of care, they must account for current epidemiologic trends. This article reviews the current epidemiology of IMD in the United States, highlighting known risk factors. Prior ACIP recommendations (and their rationale) since the approval of the first quadrivalent conjugate meningococcal vaccine in 2005 are summarized. The scientific and logistical issues associated with extending those recommendations to include infants and other at-risk groups are also discussed.