Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations Between Genetic Variants in the IRGM Gene and Inflammatory Bowel Diseases in the Korean Population

Background:Recent European ancestry genome-wide association studies have identified genetic variants of IRGM as significant susceptibility loci for Crohn's disease (CD). Therefore, we investigated whether genetic variants of IRGM confer genetic susceptibility to CD or ulcerative colitis (UC) and evaluated the genotype–phenotype associations in the Korean population. Methods:This study included 510 inflammatory bowel disease (IBD) patients (253 patients with CD and 257 with UC) and 520 healthy controls in Koreans. Initially, we performed direct sequencing analysis to identify unique IRGM single nucleotide polymorphisms (SNPs). Three selected haplotype-tagging SNPs and one risk locus (rs72553867, rs10065172, rs4958847, and rs12654043) within the IRGM were then geno-typed in patients and controls. Results:IRGM SNP rs10065172 was significantly associated with CD susceptibility in terms of allelic frequency (P = 0.004; odds ratio [OR] = 1.42) and genotype frequency (dominant model, P = 0.008; OR = 1.62). We also found a relationship between SNP rs72553867 and CD susceptibility in the analysis of allelic frequency (P = 0.0117; OR = 0.67) and genotype frequency (dominant model, P = 0.002; OR = 0.55). In addition, we observed that the association of CD with rs10065172 became stronger in patients with younger age at diagnosis (⩽20 years) or male gender. However, there was no significant association between the four SNPs and UC susceptibility. Conclusions:This is the first study to identify SNP rs10065172 and rs72553867 in IRGM as principal CD susceptibility loci in an Asian population.
The secreted antigen, HP0175, of Helicobacter pylori links the unfolded protein response (UPR) to autophagy in gastric epithelial cells

Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis. Pathogen‐elicited host cell autophagy may favour containment of infection or may help in bacterial survival. Pathogens have developed the ability to modulate host autophagy. The secreted antigen HP0175, a peptidyl prolyl cis,trans isomerase of Helicobacter pylori, has moonlighting functions with reference to host cells. Here we show that it executes autophagy in gastric epithelial cells. Autophagy is dependent on the unfolded protein response (UPR) that activates the expression of PKR‐like ER kinase (PERK). This is accompanied by phosphorylation of eukaryotic initiation factor 2α (eIF‐2α) and transcriptional activation of ATF4 and CHOP. Knockdown of UPR‐related genes inhibits the conversion of LC3I to LC3II, a marker of autophagy. The autophagy‐inducing ability of H. pylori is compromised when cells are infected with an isogenic hp0175 mutant. Autophagy precedes apoptosis. Silencing of BECLIN1 augments cleavage of caspase 3 as well as apoptosis. Increased apoptosis of gastric epithelial cells is known to be linked to H. pylori‐mediated gastric inflammation and carcinogenesis. To the best of our knowledge, this study provides the first demonstration of how HP0175 endowed with moonlighting functions links UPR‐dependent autophagy and apoptosis during H. pylori infection.
Injection of mice with antibody to interferon enhances the growth of transplantable murine tumors

Injection of DBA/2, C57Bl/6, or BALB/c mice with antibody to mouse interferon alpha/beta enhanced the i.p. transplantability of six different murine tumors, as manifested by an increase in the percentage of tumor-bearing mice and a decrease in survival time. The effect was observed in mice injected with antibody to interferon raised in three sheep, a goat, and a rabbit, but not with sheep antibody to "impurities" present in the mouse interferon preparations or with normal sheep or goat globulins. The enhancement in transplantability was most marked when tumor cells had been previously passaged in vitro and were of low tumorigenicity. Analysis of some of the experimental conditions using interferon-sensitive and interferon-resistant lines of Friend erythroleukemia cells (FLC) showed that the enhancing effect was observed over a wide range of tumor cell inocula, was directly related to the amount of antibody to interferon injected and was most pronounced when antibody was administered at the time of tumor cell injection. Enhancement was also observed when FLC were injected subcutaneously (s.c.). Antibody did not act directly on the tumor cells in vitro. Although we were unable to demonstrate any biologically active interferon in mice before or after tumor cell inoculation, the results suggest that endogenous interferon is present and plays a role in inhibiting the transplantability of some murine tumors in immunocompetent mice.
SEX OFFENDERS: SPECIALISTS, GENERALISTS—OR BOTH? A 32-year Criminological Study

Sexual offending is on the political agenda but there has been little research focus on the four offence categories—indecent assault against a female, indecent assault against a male, indecency between males and unlawful sexual intercourse with a girl under 16—which together comprise the vast majority of convictions for sexual offences in England and Wales. We consider the criminal record (1963-94 inclusive) of the 6,097 males convicted of one of these offences in 1973. The results are discussed in terms of criminality, heterogeneity, dangerousness and specialization. By recognizing two levels of analysis—general crime level and sex crime level—we argue that sex offenders can be both generalists and spedalists; they may range widely across a spectrum of offences but still specialize within sexual offending.
Shaping the future of accounting in business education in Australia

This multi-stakeholder investigation with a prospective focus and conducted 25 years after the Mathews Committee Inquiry has three aims:  assess the current state of play of accounting in business education in Australia;  focus on the key challenges, issues and opportunities faced by the accounting education sector; and  develop feasible, innovative and productive ways forward to meet the many challenges faced by accounting education and to take full advantage of the opportunities identified. The key themes embraced in the investigation are as follows: professional knowledge and professional skills of accounting graduates; the inculcation of professional values, ethics and attitudes into graduates; scholarly research and its role in accounting education, creating knowledge and informing practice; and technology and innovation in learning environments. This study presents the findings drawn from interviews with individuals who are engaged actively in graduate recruitment and the ongoing professional development of accountants.
Body Mass Change and Ultraendurance Performance: A Decrease in Body Mass Is Associated With an Increased Running Speed in Male 100-km Ultramarathoners

Abstract Rüst, CA, Knechtle, B, Knechtle, P, Wirth, A, and Rosemann, T. Body mass change and ultraendurance performance: a decrease in body mass is associated with an increased running speed in male 100-km ultramarathoners. J Strength Cond Res 26(6): 1505–1516, 2012—We investigated, in 50 recreational male ultrarunners, the changes in body mass, selected hematological and urine parameters, and fluid intake during a 100-km ultramarathon. The athletes lost (mean and SD) 2.6 (1.8) % in body mass (p < 0.0001). Running speed was significantly and negatively related to the change in body mass (p < 0.05). Serum sodium concentration ([Na+]) and the concentration of aldosterone increased with increasing loss in body mass (p < 0.05). Urine-specific gravity increased (p < 0.0001). The change in body mass was significantly and negatively related to postrace serum [Na+] (p < 0.05). Fluid intake was significantly and positively related to both running speed (r = 0.33, p = 0.0182) and the change in body mass (r = 0.44, p = 0.0014) and significantly and negatively to both postrace serum [Na+] (r = −0.42, p = 0.0022) and the change in serum [Na+] (r = −0.38, p = 0.0072). This field study showed that recreational, male, 100-km ultramarathoners dehydrated as evidenced by the decrease in >2 % body mass and the increase in urine-specific gravity. Race performance, however, was not impaired because of the loss in body mass. In contrast, faster athletes lost more body mass compared with slower athletes while also drinking more. The concept that a loss of >2% in body mass leads to dehydration and consequently impairs endurance performance must be questioned for ultraendurance athletes competing in the field. For practical applications, a loss in body mass during a 100-km ultramarathon was associated with a faster running speed.
Postnatal development of a sexually dimorphic, hypothalamic nucleus in gerbils: A stereological study of neuronal number and apoptosis

Steroid‐sensitive, vocal courtship behavior is a function of a specific, hypothalamic nucleus, the sexually dimorphic area pars compacta (SDApc) in the male adult gerbil. Gender‐related differences in the number of neurons in this nucleus are evident immediately after birth. By using unbiased stereological estimates of cell numbers in Nissl‐stained, paraffin‐wax sections of brain, we investigated the mechanisms differentiating cell number between the sexes in the SDApc on postnatal days 0, 3, 6, and 15. Cell death, identified by pyknosis, was greatest in the SDApc between days 0–3 in males, whereas in females, maximum values were reached between days 3–6. Similarly, the ratio of pyknotic to normal neurons peaked between days 0–3 in males and 3–6 in females but then declined in both sexes. Pyknotic cells were seldom seen in either sex by day 15. Morphological characteristics of apoptosis including chromatin condensation, cell fragmentation, and ingestion of apoptic bodies by macrophages were all demonstrated by transmission electron microscopy. Macrophages showed specific morphological characteristics of microglia. Cell division (mitosis) was identified in the SDApc during postnatal days 0, 3, and 6 but the numbers of mitotic figures were low, negligible on day 15, and similar between the sexes. These results demonstrate that cell death and proliferation occur simultaneously in the neonatal gerbil brain. The stereological estimates of cell death in the developing SDApc indicated a lower incidence of neuronal death occurring earlier in males than in females. © 1996 Wiley‐Liss, Inc.
Virus-Bacterium Interactions in Water and Sediment of West African Inland Aquatic Systems

ABSTRACT The ecology of virioplankton in tropical aquatic ecosystems is poorly documented, and in particular, there are no references concerning African continental waters in the literature. In this study, we examined virus-bacterium interactions in the pelagic and benthic zones of seven contrasting shallow inland waters in Senegal, including one hypersaline lake. SYBR Gold-stained samples revealed that in the surface layers of the sites, the numbers of viruses were in the same range as the numbers of viruses reported previously for productive temperate systems. Despite high bacterial production rates, the percentages of visibly infected cells (as determined by transmission electron microscopy) were similar to the lowest percentages (range, 0.3 to 1.1%; mean, 0.5%) found previously at pelagic freshwater or marine sites, presumably because of the local environmental and climatic conditions. Since the percentages of lysogenic bacteria were consistently less than 8% for pelagic and benthic samples, lysogeny did not appear to be a dominant strategy for virus propagation at these sites. In the benthic samples, viruses were highly concentrated, but paradoxically, no bacteria were visibly infected. This suggests that sediment provides good conditions for virus preservation but ironically is an unfavorable environment for proliferation. In addition, given the comparable size distributions of viruses in the water and sediment samples, our results support the paradigm that aquatic viruses are ubiquitous and may have moved between the two compartments of the shallow systems examined. Overall, this study provides additional information about the relevance of viruses in tropical areas and indicates that the intensity of virus-bacterium interactions in benthic habitats may lower than the intensity in the adjacent bodies of water.
Leptographium tereforme sp. nov. and other Ophiostomatales isolated from the root-feeding bark beetle Hylurgus ligniperda in California

The redhaired pine bark beetle Hylurgus ligniperda (F.) is native to Europe but was discovered in Los Angeles, California, in 2003. This root-and stump-feeding beetle is a common vector of Ophiostomatales, which are potential tree pathogens or causes of blue stain of conifer sapwood. In this study Ophiostomatales were isolated on a cycloheximide-amended medium from 118 adult H. ligniperda collected from infested logs of Pinus halepensis and P. pinea at two sites in California. In total eight species of Ophiostomatales were identified and seven species that occasionally were isolated were unidentified. The most frequently isolated species were Ophiostoma ips and Grosmannia galeiforme, which were isolated respectively from 31% and 23% of the 118 beetles. The other species isolated included O. piceae (isolated from 9% of the beetles), O. querci (8%) and Leptographium tereforme sp. nov. (6%). Grosmannia huntii, L. serpens, three Sporothrix species, O. floccosum, O. stenoceras, two unidentified Hyalorhinocladiella sp. and a sterile fungus each were isolated from fewer then 5% of beetles. Most of the identified species already were known in USA and have been found in association with H. ligniperda in other countries. However the new species, L. tereforme, and G. galeiforme were recorded from USA for the first time, and this is the first report of L. serpens from western North America.
Salivary Flow Rates and Salivary Film Thickness in Five-year-old Children

The flow rate of unstimulated whole saliva, the volume of saliva in the mouth before (VMAX) and after (RESID) swallowing, and the surface area of the mouth were measured for determination of the average thickness of the salivary film in five-year-old children with primary dentitions. In 30 subjects of each gender, RESID was calculated from the potassium concentration in unstimulated saliva by a dilution technique. VMAX was calculated as the total of RESID plus the volume normally swallowed (the unstimulated salivary flow rate divided by the swallowing frequency). From these children, ten subjects of each gender who had no missing teeth were selected, and impressions were taken for determination of the surface area of the mouth. Aluminum foil, of known weight per unit area, was adapted to the stone models of different regions of the mouth, and the surface areas were calculated from the weights of foil. The unstimulated salivary flow rate was 0.22 ± 0.14 mL/min, the mean values of RESID and VMAX were 0.38 ± 0.11 mL and 0.50 ± 0.15 mL, respectively, and the mean total surface area of the mouth was 117.6 ± 7.6 cm2. There were no significant differences in these values due to gender. The average thickness of the salivary film in the mouth was calculated to vary between 0.06 and 0.09 mm. Although the values of salivary flow rate, RESID, and VMAX were much lower than those reported for adults, the average thickness of the salivary film was very similar to that in adults.
Bevacizumab-containing regimens after cetuximab failure in Kras wild-type metastatic colorectal carcinoma

Bevacizumab and cetuximab both improve treatment efficacy when administered with chemotherapy for metastatic colorectal carcinoma (mCRC). Cetuximab has enhanced efficacy in Kras wild-type tumors. However, inferior outcomes have been demonstrated concerning the concurrent use of bevacizumab and cetuximab with chemotherapy. There is an urgent need to define the optimal sequence of use of these two agents. With regard to the pre-clinical data that increased VEGF expression is associated with acquired resistance to anti-EGFR antibody, we performed a retrospective analysis on the outcomes of patients who received bevacizumab-containing regimens after cetuximab failure in Kras wild-type mCRC. From January 2006 to December 2011, patients who received bevacizumab-containing regimens for mCRC in our institution were reviewed. Patients were eligible for further analysis if the following criteria were met: i) Kras wild-type mCRC; ii) chemotherapy and cetuximab received as immediate prior treatment; iii) chemotherapy and bevacizumab received as the index line of treatment; and iv) imaging conducted for response evaluation. Outcome measures included median progression-free survival (mPFS) and objective response rate (ORR). Targeted adverse events were recorded in accordance with two prospective observational cohort studies; the BRiTE and BEAT studies. Fifty patients who received bevacizumab-containing regimens were reviewed and 18 of them met the criteria for further analysis. After a median follow-up of 12.1 months, the mPFS for the total group of patients was 26.3 weeks (95% CI, 19.5–33.0 weeks) with an ORR of 38.9%. Two patients (11.1%) had hypertension that required additional anti-hypertensive drugs and one patient did not survive due to a bowel perforation. No arterial thromboembolic events (ATEs), post-operative wound-healing complications (POWHCs) or grade III/IV bleeding were observed. In patients with Kras wild-type mCRC, bevacizumab-containing regimens following cetuximab failure have modest activity and manageable toxicity.
Effect of methotrexate treatment on expression levels of multidrug resistance protein 2, breast cancer resistance protein and organic anion transporters Oat1, Oat2 and Oat3 in rats

The ATP binding cassette (ABC) transporters, multidrug resistance protein 2 (Mrp2; Abcc2) and breast cancer resistance protein (Bcrp; Abcg2), and organic anion transporters (Oats) mediate excretion of methotrexate (MTX) and many other drugs. However, it is not known whether MTX treatment leads to any changes in the expression of these transporters. We examined the effect of MTX treatment on expression of Mrp2, Bcrp and Oats in rats. MTX was single injected intraperitoneally at doses of 10, 50 and 150 mg/kg, and then Western blot analysis was performed. The levels of Mrp2, Oat1 and Oat2 on day 1 after the treatment showed no significant change. Four days after injection of 150 mg/kg MTX, the Mrp2 levels in the liver and ileum, but not in the kidney, were markedly down‐regulated to 20 ± 3.6% and 8.9 ± 3.8% (mean ± SEM) of controls, respectively. Renal Oat1 and Oat3 were also down‐regulated to 56.4 ± 4.3% (Oat1) and 54.3 ± 5.5% (Oat3) of controls. These effects of MTX were almost recovered by leucovorin which rescues normal cells from MTX toxicity. MTX treatment also decreased mRNA levels of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) to 65.5 ± 17.9% and 59.6 ± 14.5% of controls in the liver, respectively. MTX treatment has no apparent effect on expression levels of Bcrp, cytochrome P450 2B6 and 3A1. In conclusion, these data indicate that MTX treatment down‐regulates expression levels of Mrp2, Oat1 and Oat3, and its effects are recovered by leucovorin. (Cancer Sci 2006; 97: 1260–1266)
Molecular and cellular cascades in seizure-induced neosynapse formation.

Limbic seizures induce in vulnerable structures, such as the hippocampal complex, morphologic changes that may contribute to the development of epilepsy. They include neuronal cell death, reactive gliosis, and neosynapse formation. In temporal lobe epilepsy patients, cell death develops in Ammon's horn and the hilus. This cell death involves both necrotic and apoptotic mechanisms and is likely responsible for the initiation of the glial reaction that consists of astroglial and macrophage proliferation and hypertrophy. Reactive astrocytes acquire the phenotypic properties of type 2 astrocytes and express trophic factors (e.g., bFGF), cell adhesion molecules (e.g., NCAM), and substrate molecules (e.g., tenascin-C). Seizures induce in the hippocampus a synaptic remodeling of mossy fibers. Mossy fiber collaterals innervate granule cell dendrites, creating recurrent excitatory circuits. We suggest that collateral branches of MF originate under the influence of trophic factors and as a consequence of an overproduction of tubulin polymers. In fact, seizures induce a transient increased expression of tubulin and microtubule-associated proteins in granule cells and mossy fibers. Navigation of mossy fiber growth cones may be facilitated by the interaction with astrocytes, which would exert this effect by producing and excreting cell adhesion and substrate molecules. In light of the results discussed here, one can suggest that in the adult brain, activated astrocytes could contribute to the process of axonal outgrowth and synaptogenesis.
Summarizing the Content of Large Traces to Facilitate the Understanding of the Behaviour of a Software System

In this paper, we present a semi-automatic approach for summarizing the content of large execution traces. Similar to text summarization, where abstracts can be extracted from large documents, the aim of trace summarization is to take an execution trace as input and return a summary of its main content as output. The resulting summary can then be converted into a UML sequence diagram and used by software engineers to understand the main behavioural aspects of the system. Our approach to trace summarization is based on the removal of implementation details such as utilities from execution traces. To achieve our goal, we have developed a metric based on fan-in and fan-out to rank the system components according to whether they implement key system concepts or they are mere implementation details. We applied our approach to a trace generated from an object-oriented system called Weka that initially contains 97413 method calls. We succeeded to extract a summary from this trace that contains 453 calls. According to the developers of the Weka system, the resulting summary is an adequate high-level representation of the main interactions of the traced scenario
Nosocomial fungal infections: epidemiology, diagnosis, and treatment.

Invasive fungal infections are increasingly common in the nosocomial setting. Furthermore, because risk factors for these infections continue to increase in frequency, it is likely that nosocomial fungal infections will continue to increase in frequency in the coming decades. The predominant nosocomial fungal pathogens include Candida spp. , Aspergillus spp. , Mucorales, Fusarium spp. , and other molds, including Scedosporium spp. These infections are difficult to diagnose and cause high morbidity and mortality despite antifungal therapy. Early initiation of effective antifungal therapy and reversal of underlying host defects remain the cornerstones of treatment for nosocomial fungal infections. In recent years, new antifungal agents have become available, resulting in a change in standard of care for many of these infections. Nevertheless, the mortality of nosocomial fungal infections remains high, and new therapeutic and preventative strategies are needed.
Effect of Azadirachta indica (neem) on the growth pattern of dermatophytes.

PURPOSE To determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) for the extracts of the leaves and seeds of the plant Azadirachta indica against various dermatophytes. METHODS Clinical isolates of dermatophytes(Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum nanum) were treated with extracts of leaves and seeds of the plant Azadirachta indica (neem) for antifungal activity by in vitro tube dilution technique. RESULTS The MIC of neem seed extracts was 31 microg/mL for all the dermatophytes tested. The neem seed extract at 15 microg/mL concentration (below MIC) was observed to be sufficient for distorting the growth pattern of the organisms tested. CONCLUSIONS The changes in growth curve of the treated dermatophytes were found to be statistically significant with reference to the untreated fungi.