Miracle-dz/UniFAR-FTUs huggingface dataset:
TGFBR2 but not SPP1 genotype modulates osteopontin expression in Duchenne muscular dystrophy muscle

A polymorphism (rs28357094) in the promoter region of the SPP1 gene coding for osteopontin (OPN) is a strong determinant of disease severity in Duchenne muscular dystrophy (DMD). The rare G allele of rs28357094 alters gene promoter function and reduces mRNA expression in transfected HeLa cells. To dissect the molecular mechanisms of increased disease severity associated with the G allele, we characterized SPP1 mRNA and protein in DMD muscle biopsies of patients with defined rs28357094 genotype. We did not find significant differences in osteopontin mRNA or protein expression between patients carrying the T (ancestral allele) or TG/GG genotypes at rs28357094. The G allele was significantly associated with reduced CD4+ and CD68+ cells on patient muscle biopsy. We also quantified transforming growth factor‐β (TGFB) and TGFB receptor‐2 (TGFBR2) mRNA in DMD muscle biopsies, given the ability of TGFB and TGFBR2 to activate SPP1 promoter region and their role in DMD pathogenesis. The amount of TGFB and TGFBR2 mRNA did not predict the amount of SPP1 mRNA or protein, while a polymorphism in the TGFBR2 gene (rs4522809) was found to be a strong predictor of SPP1 mRNA level. Our findings suggest that OPN mediates inflammatory changes in DMD and that TGFB signalling has a role in the complex regulation of osteopontin expression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Experimental Oesophagostomum bifurcum in monkeys

Oesophagostomum bifurcum larvae, cultured from human stools collected in northern Ghana, were used to establish experimental infections in monkeys. A patent infection was established in a rhesus monkey (Macaca mulatta) and this infection was used to generate larvae to inoculate additional monkeys. In all, 17 animals were inoculated. Thirteen of 15 animals developed antibodies to the infection between 19 and 62 days post inoculation (PI); two animals had a positive response before inoculation. Four of ten animals developed patent infections between 88 and 134 days and passed eggs in the faeces. Egg shedding was consistent in only one animal, but at low levels of one or two eggs per 2 mg direct smear, and extended over a 400 day period. In the other three animals, egg shedding was sporadic and of only 2–4 weeks duration. In seven animals necropsied between 19 and 22 days PI, one to 17 early fourth-stage larvae were recovered from nodules in the bowel wall; in an eighth animal examined at 314 days, six immature adult worms (early fifth stage) were recovered from nodules in the bowel wall. The morphological features and growth of these recovered larvae are described. Three animals were inoculated with larvae that had been dried for one week at 28°C; two animals began shedding eggs at 128 and 134 days PI, respectively. The present results suggest that the parasite obtained from humans is poorly adapted to lower primate hosts, and supports the concept that Oesophagostomum bifurcum found in humans and monkeys in the same geographical region of northern Ghana and Togo are distinct and that the infections in humans are not likely to represent zoonotic infections acquired from monkeys.
Factors affecting the voluntary use of internal audit: evidence from the UK

Purpose This study aims to identify the factors that lead non-financial companies listed in the UK to use an internal audit function (IAF) as a monitoring mechanism. Although the use of an IAF in the UK is voluntary, no prior research has examined the drivers for using one. Design/methodology/approach Financial and non-financial data were collected from the annual reports of 332 UK non-financial companies listed on the London Stock Exchange (LSE) Main Market. Univariate tests and multivariate logistic regression tests were used to test the research hypotheses. A theoretical framework based on both agency theory and transaction cost economics (TCE) theory was used to explain the economic factors affecting the use of an IAF. Findings The study provides evidence that firm size, level of internal risks, agency problem between owners and managers and existence of an effective audit committee are associated with the existence of an IAF. Thus, the need to have strong internal control and risk management systems and to reduce both internal and external agency costs drives companies to have an IAF. These results suggest the importance of IAF as an internal corporate governance tool and the effectiveness of UK governance regulations in monitoring the effectiveness of internal control systems. Practical implications Given the importance of the IAF’s corporate governance role, the study provides some policy implications. Regulators should pay more attention to the issue of maintaining an IAF, especially by large companies, the relationship between the IAF and other governance parties, especially the audit committee, and the disclosure of more relevant information about the IAF’s characteristics and practices. Originality/value This is the first study to examine the factors affecting the existence of the IAF within the UK’s distinctive regulatory approach of “comply or disclose reasons”. Furthermore, it provides a theoretical framework that explains how both the agency theory and TCE theory can interpret the adoption of internal audit.
Genome‐wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U‐CH1

Cytogenetic information on chordomas is rudimentary and restricted to GTG‐banding analysis of 26 cases worldwide. In this study, we present the chromosomal imbalances detected in a series of 16 chordomas (10 sacrococcyeal, five sphenooccipital, and one spinal) from 13 patients using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). On average, 3.2 losses and 4.2 gains were detected per tumor. The most common DNA copy number alterations were losses on chromosomal arms 3p (50%) and 1p (44%). Losses of 3p were detected in five of seven primary chordomas. Therefore, the loss of 3p might be an early event in chordoma genesis. The most common gains involved 7q (69%), 20 (50%), 5q (38%), and 12q (38%). Additionally, we raised the first human chordoma cell line, U‐CH1, from a recurrence of a sacral chordoma. U‐CH1 and its parent tumor had almost the same CGH profile. According to GTG‐banding and multicolor FISH, U‐CH1 has the following clonal chromosomal abnormalities: der(1)t(1;22), del(4), +del(5), +del(6), +7, del(9), del(10), +der(20)t(10;20), +21. Thus, the novel permanent human chordoma cell line U‐CH1 has chordoma‐typical cytogenetic aberrations. Our data suggest that tumor suppressor genes or mismatch repair genes (located at 1p31 and 3p14) and oncogenes (located in 7q36) might be involved in chordoma genesis. © 2001 Wiley‐Liss, Inc.
Enhancing Function Approximation Abilities of Neural Networks by Training Derivatives

A method to increase the precision of feedforward networks is proposed. It requires prior knowledge of a target’s function derivatives of several orders and uses this information in gradient-based training. Forward pass calculates not only the values of the output layer of a network but also their derivatives. The deviations of those derivatives from the target ones are used in an extended cost function, and then, the backward pass calculates the gradient of the extended cost with respect to weights, which is then used by a weights update algorithm. The most accurate approximation is obtained when the training starts with all available derivatives that are then step by step excluded from the extended cost function, starting with the highest orders up until only values are trained. Despite a substantial increase in arithmetic operations per pattern (compared with the conventional training), the method allows to obtain 140–1000 times more accurate approximation for simple cases if the total number of operations is equal. This precision also happens to be out of reach for the regular cost function. The method works well for solving differential equations with neural networks. The cost function is the deviation of the equation’s residual from zero, and it can be extended by differentiating the equation itself so no prior information is required. This extension allows to solve 2-D nonlinear partial differential equation 13 times more accurately using seven times fewer grid points. The GPU-efficient algorithm for calculating the gradient of the extended cost function is proposed.
‘No politics in the agenda-setting meeting’: plenary agenda setting in the Netherlands

Abstract The process of agenda setting is fundamental to politics, yet there is surprisingly little research about this process in parliamentary systems. The reason for this lacuna is that agenda setting tends to occur behind closed doors. The Dutch Tweede Kamer is an exception to this rule: decisions about the parliamentary agenda are made in public. This study examines agenda setting in the Dutch parliament from an issue-competition perspective. It looks at a sample of more than 400 agenda-setting meetings of the Dutch parliament between 1998 and 2017. It finds that opposition parties which stand far from the government make proposals on issues that they ‘own’; these proposals are supported by other opposition parties, parties that stand close to them and focus on the same issue. Coalition parties and parties that stand far away sabotage these proposals.
Ototoxic effects of supradose cisplatin with sodium thiosulfate neutralization in patients with head and neck cancer.

OBJECTIVE To assess the incidence and magnitude of ototoxicity in patients undergoing an experimental targeted chemoradiation protocol incorporating extremely high-dose intra-arterial cisplatin therapy with systemic sodium thiosulfate neutralization for the treatment of advanced carcinomas of the head and neck. DESIGN Inception cohort study. SETTING University-based, tertiary care referral center for advanced head and neck malignant disease. PATIENTS The first 70 patients with advanced carcinomas of the head and neck consecutively entered in the protocol. INTERVENTION Patients received up to 4 weekly courses of intra-arterial cisplatin (150 mg/m2 per infusion), together with systemic sodium thiosulfate and external beam radiation (68-70 Gy). Audiometric analysis was performed before the initiation of therapy, and subsequent to the second and fourth cisplatin infusions. MAIN OUTCOME MEASURES Audiometric thresholds. Ototoxicity was defined as an increase in pure-tone threshold of 15 dB at 1 frequency or 10 dB at 3 frequencies, between 250 and 4000 Hz. RESULTS The incidence of ototoxicity was 25% at 150 mg/m2, 50% at 300 mg/m2, 64% at 450 mg/m2, and 60% at 600 mg/m2. Hearing at frequencies of 2000 Hz or less was minimally or not affected. Previous hearing loss did not appear to affect the incidence of ototoxicity. A plateau of hearing loss at 60-dB hearing level, as noted by other authors, was not observed. There were no cases of debilitating tinnitus or of vestibular loss. CONCLUSIONS Ototoxicity did occur but was largely confirmed to the higher frequencies. Hearing losses resulting from this chemoradiation protocol were not sufficiently severe to alter its application.
N-Glycosylation of pig flavin-containing monooxygenase form 1: determination of the site of protein modification by mass spectrometry.

By using a combination of biochemical methods (i.e., endoglycosidase H digestion and immunoblot and plant lectin binding studies), it was verified that pig flavin-containing monooxygenase (FMO1) was N-glycosylated. By using mass spectrometry approaches [i.e., peptide mapping, gas chromatography/mass spectrometry, microbore HPLC/electrospray ionization mass spectrometry (LC/ESI/MS), chemical ionization gas chromatography/mass spectrometry (CI/GC/MS), and matrix-assisted laser desorption mass spectrometry (MALDI/MS)], we were able to confirm that pig FMO1 was N-glycosylated and we were able to identify the site of N-glycosylation. Pig FMO1 contains two putative consensus sites of N-glycosylation. The results showed that pig FMO1 amino acid Asn120 was selectively N-glycosylated. Highly purified pig FMO1 avidly bound concanavalin A and reacted positively for carbohydrates by the periodic acid/Schiff's base method of analysis. In addition, treatment of pig FMO1 with endo-N-acetylglucosaminidase converted the enzyme to another species with a molecular mass approximately 5000 Da lower than that of the parent protein as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot experiments. Peptide mapping of pig FMO1 showed that the protein used in the study was not contaminated with another glycoprotein. MALDI/MS experiments showed that pig FMO1 was present with the expected molecular mass but that higher-molecular mass forms consistent with the presence of N-linked high-mannose oligosaccharide structures were also covalently attached to the enzyme. The presence of N-acetylglucosamine isolated from acid hydrolysates of the N-linked high-mannose oligosaccharide of pig FMO1 was confirmed by high-pH anion exchange HPLC studies and verified by CI/GC/MS studies of derivatized monosaccharide fractions. Further analysis of pig FMO1 proteolytic peptides by LC/ESI/MS showed that the only residue that was N-glycosylated in pig FMO1 was Asn120. Knowledge of the structural aspects of FMO may be useful in understanding the membrane association properties of the enzyme.
Leveling curve of Spee and its effect on mandibular arch length.

OBJECTIVE To determine the additional space required for leveling of curve of Spee in the mandibular arch by continuous arch wire mechanics. STUDY DESIGN Quasi-experimental interventional. SETTING Orthodontics Department, Karachi Medical and Dental College from September 2002 to September 2004. SUBJECTS AND METHODS Depth of curve of Spee and arch length were measured on 40 pre-treatment and posttreatment plaster models with the help of sharpened Boley gauge. RESULT The study showed that clinical practice of allowing 1 mm of arch circumference for leveling each millimeter of curve of Spee overestimates the amount of arch space needed to flatten the curve of Spee (p < 0.001). CONCLUSION The result suggested that the belief that 1 mm of arch circumference was necessary to level each millimeter of curve of spee present was an overestimation.
Long-Pulsed 532-Nm Neodymium-Doped Yttrium Aluminium Garnet Laser for Treatment of Facial Plane Warts in 160 Yemeni Patients

BACKGROUND Warts in general and plane warts in particular pose a therapeutic challenge for dermatologists. Many treatment modalities exist, with variable success rates, side effect profiles, and precautions. The long-pulsed 532-nm neodymium-doped yttrium aluminium garnet (LP Nd:YAG) laser has not been previously used for this indication. OBJECTIVE This study was conducted to assess the efficacy and safety of the LP Nd:YAG laser for treating facial plane warts. MATERIALS AND METHODS A total of 160 Yemeni patients (62 women, 98 men; age range, 5–55 years) were exposed to 1 laser treatment session with the following parameters: wavelength, 532 nm; pulse duration, 20 millisecond; spot size, 2 to 3 mm; and fluence, 25 J/cm2. The end point was graying or whitening of the lesion. Color photographs were taken before and immediately after treatment and at follow-up visits 1, 4, and 16 weeks after the laser session. RESULTS An overall clearance rate of 92% after only one session was achieved, with minimal and transient side effects. CONCLUSION The LP Nd:YAG laser is safe and effective for treating facial plane warts, with a success rate of 92% after only one session.
Folate intake and breast cancer prognosis: a meta-analysis of prospective observational studies

Some studies have investigated the association between folate intake and breast cancer prognosis, but the results have been far from conclusive. Thus, a meta-analysis was carried out to explore this association. We performed a comprehensive search of the PubMed, Web of Knowledge, and Cochrane databases from inception to May 2013. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random effects model. Prespecified stratified analyses, sensitivity analyses, and dose–response analysis were also carried out. Five studies, with a total of 7299 participants, were included in the meta-analysis. The pooled HR (95% CI) of the five studies on the association of dietary folate intake (highest vs. lowest) with all-cause mortality was 0.74 (0.60–0.92). Stratified analyses suggested that the inverse association of dietary folate and all-cause mortality was more easily detected in studies that focused on prediagnosis diets, included more patients (>1000), had longer follow-up periods (>7 years), used structured interviews, or had more categories of folate intake (>3). However, none of these differences was statistically significant. No significant association was found between total (dietary and supplementary) folate intake and all-cause mortality, or dietary folate intake and breast cancer-specific mortality, with pooled HRs (95% CI) of 0.93 (0.75–1.15) and 0.79 (0.61–1.01), respectively. Sensitivity analyses confirmed the robustness of the findings by excluding studies that poorly represented the cohort. Our findings suggest a significant inverse association between dietary folate intake and all-cause mortality, but not between total folate intake and all-cause mortality.
Efficacy of in‐office bleaching techniques combined with the application of a casein phosphopeptide‐amorphous calcium phosphate paste at different moments and its influence on enamel surface properties

OBJECTIVES: The aim of this in vitro study was to investigate the efficacy of in‐office bleaching technique combined with the application of a casein phosphopeptide‐amorphous calcium phosphate (CPP‐ACP) paste (MI Paste–MI) at different moments and its influence on enamel surface properties. METHODS: Eighty bovine dental crowns were randomly allocated into eight groups (n = 10), and bleached with either 35% hydrogen peroxide (HP) or 37% carbamide peroxide (CP). Four different protocols of application of MI were considered: without MI, MI applied before bleaching, MI applied after bleaching, and MI applied both before and after bleaching. Bleaching effectiveness was measured by the VITA EasyShade spectrophotometer utilizing the CIEL*a*b* system (ΔE, ΔL*, Δa*, and Δb*). Color readings were measured at baseline, 7, 14, and 21 days. Hardness and roughness were measured at baseline (T0) and immediately after bleaching (T14). Data were subjected to the two‐way ANOVA for repeated measurements and Tukey's test at 5%. RESULTS: HP groups achieved the greatest color change. The application of a CPP‐ACP paste did not reduce the efficacy of bleaching peroxides. Samples bleached with CP showed decreased hardness at T14. Samples bleached with HP that received the application of MI before and before/after bleaching did not present hardness decrease at T14. Samples bleached with peroxides only and received MI after bleaching showed increased roughness at T14. CONCLUSIONS: The use of CPP‐ACP was able to prevent negative changes in roughness and hardness of bovine enamel when associated to hydrogen peroxide, and might be applied before/after the bleaching protocol. Microsc. Res. Tech. 75:1019–1025, 2012. © 2012 Wiley Periodicals, Inc.
Chronic lymphocytic leukemia--correlation of response and survival.

Chronic lymphocytic leukemia (CLL) is considered to be an incurable hematologic malignancy using conventional therapy. Complete remissions (CR) were unusual with conventional approaches such as chlorambucil with or without prednisone or cyclophosphamide, vincristine, and prednisone (CVP). Pathologic complete remissions including negative bone marrow biopsies were seldom mentioned in the literature. Two parameter flow cytometry has demonstrated that CLL cells co-express CD5 and pan-B cell antigens such as CD19 and CD20. In addition, immunoglobulin gene rearrangement occurs predictably in B-cell CLL and can be used as a further marker of completeness of remission. The National Cancer Institute (NCI) has published criteria for complete remission which allow persistent lymphoid nodules to be present on the bone marrow biopsy and the patient can be considered in complete remission. Our group has considered these patients to have a nodular CR (Nod CR) to separate them from having a true remission on bone marrow biopsy (CR-bx). Thus bone marrow biopsy criteria, two parameter flow cytometry, and immunoglobulin gene rearrangement are now available for routine clinical application to re-define completeness of remission in CLL. With the use of fludarabine monophosphate (Fludara), complete and partial responses are obtained in 50-55% of previously treated patients with CLL and 75-80% of patients with previously untreated CLL. There was a strong correlation of probability of response with degree of previous therapy, stage of disease, age, hemoglobin level, platelet count, serum albumin and beta 2-microglobulin, and bone marrow infiltration with lymphocytes. Patients can be identified as being at high/low risk of achieving a complete or partial response. (ABSTRACT TRUNCATED AT 250 WORDS)
In Vitro Exposure of Porcine Ovarian Follicular Cells to PCB 153 Alters Steroid Secretion But Not Their Viability—Preliminary Study

In our previous paper[1], we demonstrated that porcine follicles collected during the early stage of development are the most sensitive to the toxic action of polychlorinated biphenyl 153 (PCB 153). Follicles of this type were collected to test the effect of PCB 153 on cell steroidogenesis and viability. Cocultures of granulosa and theca cells were grown in M199 medium at 37ºC. Control cultures were maintained in that medium alone, while experimental ones were supplemented with PCB 153 at doses of 5, 10, 50, and 100 ng/ml. After 48, 96, and 144 h, media were collected for steroid analysis and cell viability was measured using an LDH (lactate dehydrogenase activity) cytotoxicity test. A 2-day exposure of follicular cells to all the investigated doses of PCB 153 caused a statistically significant decrease in progesterone (P4) secretion, while in doses of 50 and 100 ng/ml there was also a decrease in testosterone (T) secretion. No effect on estradiol (E2) secretion was observed. The observed decrease in P4 and T secretion, and lack of any statistically significant effect on E2 secretion by cells from small follicles exposed for 48 h to PCB, suggests that PCB 153 acts before P4 formation. Longer exposures caused an increase in P4 secretion, with a concomitant drastic decrease in T secretion and a tendency to decrease the E2 secretion, suggesting inhibition of P450 17α hydroxysteroid dehydrogenase, an enzyme that converts P4 to T. The observed PCB 153–induced increase in P4 secretion by cells collected from small antral follicles, with a concomitant decrease in E2 secretion, accounts for the induction of luteinization and, in this case, inhibition of aromatization process in the follicles. However, in all doses tested and at all times of exposure, PCB 153 had no effect on cell viability. These findings suggest different time of exposure–dependent action of PCB 153 on particular steps of steroidogenesis but not action on cell viability. These results should be considered preliminary, pending confirmation by other studies.