Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased risk of type 1 diabetes in Polish children - association with INS-IGF2 5'VNTR and lack of association with HLA haplotype.

BACKGROUND Human leukocyte antigens (HLA) complex and INS-IGF2 5'VNTR loci are principal determinants of the risk of type 1 diabetes mellitus (T1DM). Carriage of class III allele is protective, while class I/I homozygosity increases the risk of T1DM. MATERIAL AND METHODS HLA and 5'VNTR allele frequencies were summarised and multivariate logistic regression models with interaction evaluation were employed to determine the presence and types of allele effect interdependency. The study group was planned to number 590 children who would undergo genotyping of 5'VNTR and HLA. RESULTS 590 patients (302 with T1DM and 288 controls) were recruited. Frequencies of HLA risk alleles were: 117 carriers of DR3-DQ2; 130 carriers of DR4-DQ8 including 43 DR3-DQ2/DR4-DQ8 heterozygotes. In all cases, risk alleles were vastly overrepresented in the T1DM group compared to the controls (p < 0.0001 in all cases). The most frequent protective haplotype was DQB1 × 0602 observed in 24 controls and two T1DM cases (p < 0.001). Class I 5'VNTR homozygotes constituted 58% of the control group (n = 174) and 78% (n = 224) of T1DM patients [OR = 2.63 (95% CI: 1.79-3.57)]. Interactions between 5'VNTR and DR3-DQ2 or DR4-DQ8 variants did not reach statistical significance for risk of developing T1DM (p = 0.54 and 0.24) or age at its diagnosis (p = 0.14 and 0.67 respectively). CONCLUSIONS Interactions between HLA and 5'VNTR genotype are not of multiplicative character. Class I homozygosity at 5'VNTR is a significant risk factor of T1DM and acts independently from HLA haplotype in determining the actual risk of diabetes in children.
Hot and not‐so‐hot females: reproductive state and thermal preferences of female Arizona Bark Scorpions (Centruroides sculpturatus)

For ectotherms, environmental temperatures influence numerous life history characteristics, and the body temperatures (Tb) selected by individuals can affect offspring fitness and parental survival. Reproductive trade‐offs may therefore ensue for gravid females, because temperatures conducive to embryonic development may compromise females' body condition. We tested whether reproduction influenced thermoregulation in female Arizona Bark Scorpions (Centruroides sculpturatus). We predicted that gravid females select higher Tb and thermoregulate more precisely than nonreproductive females. Gravid C. sculpturatus gain body mass throughout gestation, which exposes larger portions of their pleural membrane, possibly increasing their rates of transcuticular water loss in arid environments. Accordingly, we tested whether gravid C. sculpturatus lose water faster than nonreproductive females. We determined the preferred Tb of female scorpions in a thermal gradient and measured water loss rates using flow‐through respirometry. Gravid females preferred significantly higher Tb than nonreproductive females, suggesting that gravid C. sculpturatus alter their thermoregulatory behaviour to promote offspring fitness. However, all scorpions thermoregulated with equal precision, perhaps because arid conditions create selective pressure on all females to thermoregulate effectively. Gravid females lost water faster than nonreproductive animals, indicating that greater exposure of the pleural membrane during gestation enhances the desiccation risk of reproductive females. Our findings suggest that gravid C. sculpturatus experience a trade‐off, whereby selection of higher Tb and increased mass during gestation increase females' susceptibility to water loss, and thus their mortality risk. Elucidating the mechanisms that influence thermal preferences may reveal how reproductive trade‐offs shape the life history of ectotherms in arid environments.
Parent and Child Perspectives on the Presence and Meaning of Parental Television Mediation

A survey of 394 parents and second- through sixth-grade children was conducted to understand why parents mediate violent television and how children interpret mediation messages. The study found that parents with negative attitudes toward violent television used active and restrictive mediation and parents with positive attitudes used coviewing. According to children, restrictive mediation signaled parental disapproval of the content but active mediation and coviewing served as endorsements.
Histopathological responses in the CNS following inoculation with a non‐neurovirulent mutant (1716) of herpes simplex virus type 1 (HSV 1): relevance for gene and cancer therapy

The RL1 gene of herpes simplex virus (HSV) encodes a polypeptide, ICP34.5 which is a specific virulence determinant. RL1 null mutants fail to replicate in both the PNS and CNS and are incapable of causing encephalitis. Additionally, RL1 null mutants have the capacity to replicate in actively dividing cells but fail to replicate in growth arrested or terminally differentiated cells. This selective replication phenotype has highlighted their use as both tumour killing agents and gene delivery vehicles particularly to the nervous system. Before their full potential can be assessed, however, it is necessary to determine the pathological and immune responses induced following direct intracerebral inoculation. Fourteen mice were injected in the left cerebral hemisphere with a high dose of the HSV‐1, RL1 null mutant 1716. At regular time intervals up to 28 days, the mice were killed and the distribution of virus antigen, histopathological changes and immune responses in the CNS determined by H & E staining and immunohistochemistry. Control mice were injected with either wild type HSV‐1 or buffer. At early times post‐ inoculation with 1716, there is a low grade meningoencephalitis with a limited inflammatory response. This is accompanied by virus antigen expression confined to the site of inoculation. By 28 days the CNS is histopathologically normal; virus antigen and immune responses are no longer detectable. These findings demonstrate that infection of the CNS by RL1 null mutants of HSV results in a finite, self‐limiting response and highlights their potential for therapeutic use.
Medical curricula in China and the USA: a comparative study

To examine the differences between the content of curriculum of medical schools in China and the USA the authors compared the curricula of 82 Chinese and 125 American medical colleges. Great disparities were found in the framework of medical curricula, processes of teaching/learning, types and numbers of preclinical courses, course hours, laboratory and practical training hours, and key disciplines of clinical practice. A significant difference was also found in the number of courses, lectures and laboratory and clerkship hours among Chinese medical colleges. The authors conclude that medical colleges in China should look again at the type of courses offered, revise curricular frameworks and reform the teaching/learning process and approaches. New courses should be introduced, new content should be added to existing courses, and appropriate importance should be attached to clinical practice of subjects such as family and community medicine. To improve the quality of medical education, Chinese medical colleges need national medical education standards compatible with international standards.
Are cold winters in Europe associated with low solar activity?

Solar activity during the current sunspot minimum has fallen to levels unknown since the start of the 20th century. The Maunder minimum (about 1650–1700) was a prolonged episode of low solar activity which coincided with more severe winters in the United Kingdom and continental Europe. Motivated by recent relatively cold winters in the UK, we investigate the possible connection with solar activity. We identify regionally anomalous cold winters by detrending the Central England temperature (CET) record using reconstructions of the northern hemisphere mean temperature. We show that cold winter excursions from the hemispheric trend occur more commonly in the UK during low solar activity, consistent with the solar influence on the occurrence of persistent blocking events in the eastern Atlantic. We stress that this is a regional and seasonal effect relating to European winters and not a global effect. Average solar activity has declined rapidly since 1985 and cosmogenic isotopes suggest an 8% chance of a return to Maunder minimum conditions within the next 50 years (Lockwood 2010 Proc. R. Soc. A 466 303–29): the results presented here indicate that, despite hemispheric warming, the UK and Europe could experience more cold winters than during recent decades.
Single-port transumbilical laparoscopic cholecystectomy: a preliminary study in 37 patients with gallbladder disease.

INTRODUCTION Since the introduction of laparoscopic surgery, surgeons have not only been concerned about clinical outcomes, but also surgical scars. Although natural orifice transluminal endoscopic surgery (NOTES) is promising, it is not applicable to clinical practice thus far due to safety concerns. As a transitional procedure between standard laparoscopic surgery and NOTES, single-port transumbilical laparoscopic surgery might be an ideal alternative. The main advantage of single-port transumbilical laparoscopic surgery is that it is performed with existing instruments. Thus, we applied single-port surgery for cholecystectomies and the clinical outcomes were analyzed. METHODS Between July and October 2008, 37 adults with gallbladder pathologies were enrolled in this study. Only one transumbilical incision was made for accessing the abdominal cavity and a multichannel port system was assembled with existing devices. Standard laparoscopic instruments were used to perform the cholecystectomy. RESULTS There were 13 males and 24 females. The mean age of the patients was 47.5 +/- 12.2 years. Twenty-nine patients had gallbladder stones, 7 patients had gallbladder polyps, and 1 patient had biliary dyskinesia. The mean operative time was 83.6 +/- 40.2 minutes. Gallbladder perforations occurred in 11 patients. In 5 patients, the procedure was converted to a standard laparoscopic technique due to technical difficulties. Complications occurred in 2 patients; specifically, a mesenteric injury was caused by the inadvertent grasping of the small-bowel mesentery during the removal of the wound retractor and an inadvertent injury of the right hepatic duct. The mean hospital stay was 2.7 +/- 1.5 days. CONCLUSIONS Our series has demonstrated the feasibility and safety of single-port transumbilical laparoscopic cholecystectomy. When technical difficulties arise, early conversion to a standard laparoscopic technique is advised to avoid serious complications. Additional studies randomizing standard laparoscopic cholecystectomy and single-port transumbilical cholecystectomy are necessary for defining the exact role of this procedure.
Targeting and assembly of components of the TOC protein import complex at the chloroplast outer envelope membrane

The translocon at the outer envelope membrane of chloroplasts (TOC) initiates the import of thousands of nuclear encoded preproteins required for chloroplast biogenesis and function. The multimeric TOC complex contains two GTP-regulated receptors, Toc34 and Toc159, which recognize the transit peptides of preproteins and initiate protein import through a β–barrel membrane channel, Toc75. Different isoforms of Toc34 and Toc159 assemble with Toc75 to form structurally and functionally diverse translocons, and the composition and levels of TOC translocons is required for the import of specific subsets of coordinately expressed proteins during plant growth and development. Consequently, the proper assembly of the TOC complexes is key to ensuring organelle homeostasis. This review will focus on our current knowledge of the targeting and assembly of TOC components to form functional translocons at the outer membrane. Our analyses reveal that the targeting of TOC components involves elements common to the targeting of other outer membrane proteins, but also include unique features that appear to have evolved to specifically facilitate assembly of the import apparatus.
Critical role for the mediodorsal thalamus in permitting rapid reward-guided updating in stochastic reward environments

Adaptive decision-making uses information gained when exploring alternative options to decide whether to update the current choice strategy. Magnocellular mediodorsal thalamus (MDmc) supports adaptive decision-making, but its causal contribution is not well understood. Monkeys with excitotoxic MDmc damage were tested on probabilistic three-choice decision-making tasks. They could learn and track the changing values in object-reward associations, but they were severely impaired at updating choices after reversals in reward contingencies or when there were multiple options associated with reward. These deficits were not caused by perseveration or insensitivity to negative feedback though. Instead, monkeys with MDmc lesions exhibited an inability to use reward to promote choice repetition after switching to an alternative option due to a diminished influence of recent past choices and the last outcome to guide future behavior. Together, these data suggest MDmc allows for the rapid discovery and persistence with rewarding options, particularly in uncertain or changing environments. DOI: http://dx.doi. org/10.7554/eLife.13588. 001
AN ANALYSIS OF THE MATERNAL AND FOETAL WEIGHT FACTORS IN NORMAL PREGNANCY

ALMOST a century has passed since Gassner (1 862) focused his attention on maternal weight gain during pregnancy. Since that time a great deal has been written concerning the maternal and foetal weight factors in pregnancy, though much that has been written is of little statistical value due in part to an inadequacy of numbers and in part to generally faulty statistical technique. The majority of workers suggest that toxaemic patients tend to gain more weight than normally pregnant women (Chesley and Chesley, 1943; Dawson and Borg, 1949; Evans, 1937; Hamlin, 1952; Harding and Van Wyck, 1934; McIlroy and Rodway, 1937; Stander and Pastore, 1940; Wodon, 1935; Zangemeister, 1916), and with this in mind all toxaemic patients have been excluded from the survey. It was felt that a statistically acceptable analysis of the maternal and foetal weight factors in normal pregnancy was desirable as a basis for much research that has yet to be done on pathological weight gain, water retention, adrenal control of water and nitrogen balance, etc.
Cloning of a Second Arabidopsis Peptide Transport Gene

Previously, we reported the isolation of a peptide transport gene designated AtPTR2 from Arabidopsis thaliana by functional complementation of a yeast peptide transport mutant. We now report the isolation of a second peptide transport gene (AtPTR2-B) from Arabidopsis using the same approach. Similar to the effects of transferring AtPTR2-A (previously called AtPTR2), transfer of AtPTR2-B to yeast peptide transport mutants restored the ability to grow on di- and tripeptides but not peptides four residues or longer. However, unlike yeast mutants complemented with either the yeast PTR2 gene or the AtPTR2-A gene, transformants expressing AtPTR2-B were only partially sensitive to toxic peptides. Northern analysis showed that AtPTR2-B was constitutively expressed in all plant organs. Studies of the kinetics indicated that AtPTR2-A and AtPTR2-B have Km values of 47 and 14 [mu]M, respectively, with Vmax values of 0.061 and 0.013 nmol mg-1 cell dry weight s-1, respectively, when dileucine was used as a substrate. AtPTR2-B is encoded on a 2.0-kb cDNA corresponding to a 585-amino acid protein (64.4 kD). Hydropathy analysis indicates that the protein is highly hydrophobic and suggests that there are 12 putative transmembrane segments. AtPTR2-B, like AtPTR2-A, shares significant similarity to a number of other proteins involved in transport of peptides into cells.
The Effects of Geographical Distance on the Decision to Enrol in University Education

This study uses data on a large sample of Swedes born in 1967 to investigate whether geographical distance between the area of residence and the nearest university influences individuals decisions to enrol in university education. Models that control for results on intelligence tests obtained at the age of 13, parental education and parental occupation predict a small but significantly negative effect of distance on the likelihood of starting a university education. If distance is related to the costs of investing in university education, then the result might suggest that the educational policy to decentralise higher education to some extent has been successful in reducing the costs of making this investment.
Energy efficiency optimization for D2D communications based on SCA and GP method

In this paper, we propose an energy-efficient power control scheme for device-to-device (D2D) communications underlaying cellular networks, where multiple D2D pairs reuse the same resource blocks allocated to one cellular user. Taking the maximum allowed transmit power and the minimum data rate requirement into consideration, we formulate the energy efficiency maximization problem as a non-concave fractional programming (FP) problem and then develop a two-loop iterative algorithm to solve it. In the outer loop, we adopt Dinkelbach method to equivalently transform the FP problem into a series of parametric subtractive-form problems, and in the inner loop we solve the parametric subtractive problems based on successive convex approximation and geometric programming method to obtain the solutions satisfying the Karush-Kuhn-Tucker conditions. Simulation results demonstrate the validity and efficiency of the proposed scheme, and illustrate the impact of different parameters on system performance.
Diversity in online learners: Searching for differences that may matter

Online learning environments increasingly provide opportunities for interaction with and among individuals from diverse cultures. The more we acknowledge and understand the nature of diversity amongst online learners, the greater the opportunity to build effective, supportive learning environments for all. Given the almost limitless diversity between individuals an important first step is to identify dimensions that may affect the online learning experience. This paper provides a preliminary study to identify relevant diversity dimensions based on a review of the literature. It is intended to inform future research to derive principles of instructional design for creating effective online learning environments.
Victoria's Serious Sex Offenders Monitoring Act 2005: Implications for the Accuracy of Sex Offender Risk Assessment

Victoria's new Serious Sex Offenders Monitoring Act 2005 established a new regime whereby high-risk child-sex offenders can receive intensive, long-term supervision in the community post incarceration. Motivation for the new Act stemmed from increasing public outcry regarding a small number of known child-sex offenders sexually recidivating, and presumes that this recidivism should have been, and could have been, predicted and therefore prevented. The present article reviews the nature and purpose of this new sex offender legislation, and discusses some of the theoretical, practical and clinical issues in forensic psychiatric and psychological research highlighted by its implementation. The sole focus of the legislation on child-sexual offenders implies that these offences are more severe, or more recidivistic, than other sexual or violent crimes, a contention that is not wholly supported by the literature. Furthermore, research on many of the crimes specified under the Act is limited, and many questions remain unanswered regarding our ability to predict sexual recidivism, particularly in legal contexts where the consequences of false predictions are so severe. Further research on base rates and risk prediction of these specific offences, and in Australian populations, is required in order to justify the conclusions on which this law is based.
MicroRNA-145 inhibits migration and invasion by down-regulating FSCN1 in lung cancer.

BACKGROUND The extraordinary invasive capability is a major cause of treatment failure and tumor recurrence in lung cancer. Evidence in other cell systems has implicated the regulatory role of microRNA-145 in cell motility and invasion, which promotes us to investigate the biological functions of miR-145 in lung cancer in this regard. RESULTS We have found that miR-145 is dramatically down-regulated in clinical specimen of lung cancer and is negatively correlated with the tumor pathological grading in the current study. The cells transfected by miR-145 expression vector have demonstrated retarded cell mobility. Using a bioinformatics analysis approach, fascin homolog 1 (FSCN1), actin-binding protein, has been identified as the target of miR-145. Over-expression of miR-145 mimics enhanced protein levels of E-cadherin and fibronectin, indicative of its inhibitory role in EMT occurrence. Mechanistic studies showed that miR-145 mimics inhibited FSCN1 expression and miR-145 inhibitor enhanced it. Over-expression of FSCN1 reversed miR-145-regulated expression of EMT markers, suggesting that FSCN1 mediated the inhibitory effects of miR-145. Our results revealed a novel mechanism that miR-145 inhibits lung cancer cells migration and invasion via FSCN1 downregulation. CONCLUSIONS These results suggest that miR-145 may function as anti-migration and anti-invasion influence in lung cancer and provides a potential approach for developing miR-145-based therapeutic strategies for malignant lung cancer therapy.
High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types.

BACKGROUND Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid beta-peptide (Abeta)-centric theory holds that Abeta is involved in the pathogenesis of sporadic AD. Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes lead to increased Abeta levels before symptoms arise. OBJECTIVES To evaluate the pattern of Pittsburgh Compound B (PiB) retention in subjects with different autosomal dominant mutations associated with familial AD vs that in healthy age-matched control subjects and subjects with probable sporadic AD, to correlate Abeta burden as measured by PiB with available clinical and cognitive data, and to compare the regional brain patterns of PiB retention and fluorodeoxyglucose F 18 (FDG) uptake. DESIGN Correlation analysis of positron emission tomography (PET) imaging studies. SETTING Academic research. PARTICIPANTS Seven PSEN1 mutation carriers and 1 APP mutation carrier underwent PiB and FDG PET imaging. Amyloid beta-peptide burden and FDG uptake were established using standardized uptake values normalized to pons. MAIN OUTCOME MEASURE Primary outcomes were PET results, which were compared with those of a well-characterized cohort of 30 healthy control subjects and 30 subjects with probable sporadic AD. RESULTS All mutation carriers had high PiB retention in the striatum, with some also having cortical PiB retention in ventrofrontal and posterior cingulate/precuneus areas. The striatal pattern of PiB retention was similar in the PSEN1 and APP mutation carriers. Neither striatal nor cortical Abeta burden was related to cognitive status. CONCLUSIONS Consistent with previous studies, the pattern of Abeta deposition in familial AD differs from that in sporadic AD, with higher striatal and somewhat lower cortical PiB retention in familial AD. The pattern and degree of Abeta deposition were not associated with mutation type nor cognitive status.