Miracle-dz/UniFAR-FTUs huggingface dataset:
High frequency of microsatellite instability in young patients with head‐and‐neck squamous‐cell carcinoma: Lack of involvement of the mismatch repair genes hMLH1 AND hMSH2

The most prevalent risk factors in the development of head‐and‐neck squamous‐cell carcinoma (HNSCC) are excessive tobacco and alcohol consumption. In young patients with HNSCC, these risk factors are often absent. Our purpose was to investigate the risk factors, microsatellite instability (MSI) changes and status of the mismatch repair genes hMLH1 and hMSH2 in a cohort of young patients with HNSCC. Fifty‐seven HNSCC tumors were examined for the presence of MSI at 16 microsatellite sites using PCR. In the young patient group (24 cases, ≤44 years old), 100% of tumors had MSI at 1 site at least and 88% had MSI at 2 or more loci. In older patients (33 cases, ≥45 years), MSI at 1 or more sites was found in 61% of tumors (young vs. old, p = 0.0003) and instability at 2 or more sites was found in 36% of tumors (young vs. old, p = 0.0001). The involvement of the mismatch repair genes was investigated by examining promoter methylation, exon mutation and gene expression of hMLH1 and hMSH2. All results were negative, indicating that inactivation of these 2 genes does not play a role in the development of MSI in tumors from this patient group. Furthermore, the young patient group had a significantly lower incidence of smoking (46% young, 88% old; p = 0.001) and alcohol consumption (33% young, 67% old; p = 0.0169), emphasizing the probable importance of other environmental and/or genetic factors in the development of their disease. © 2001 Wiley‐Liss, Inc.
Quantification of Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different Patterns of Virological Response to Interferon Therapy in Chronically Infected Patients

ABSTRACT Hepatitis delta virus (HDV), in association with hepatitis B virus, is responsible for severe acute and chronic hepatitis. Treatment of the infection relies on the long-term administration of high doses of alpha interferon (IFN), and the treatment efficiency is monitored by the detection of anti-HDV immunoglobulin M and HDV genome in serum. Like the case for other chronic viral infections, HDV genome quantification in serum should be useful for the follow-up of infected patients. The aims of this study were to develop a quantitative assay for the detection of any type of HDV in serum and to evaluate the benefit of HDV RNA quantification for the follow-up of chronically infected patients receiving IFN. A real-time reverse transcription-PCR assay was developed to quantify the HDV RNA load in serum. Its efficacy was evaluated with 160 serum samples, 76 of which were collected from 11 chronically infected patients who were treated with pegylated IFN. The assay was sensitive (100 copies/ml of serum) and efficient for all HDV types, including type 3 and the recently described types 5, 6, and 7. The viral load determinations for treated patients allowed us to identify different profiles of virological responses to IFN therapy with more accuracy than that attainable with the qualitative approach. In conclusion, we have developed a quantitative HDV RNA assay for serum which is adapted to the follow-up of antiviral treatment for patients infected with any HDV type. The assay will help us to understand the natural history of HDV infection and to define guidelines for the management of chronic delta hepatitis.
Screening Community Pharmacy Patients for Risk of Prescription Opioid Misuse

Objectives:This study tested screening feasibility and described the behavioral, mental, and physical health of patients filling prescriptions for opioid medications in the community pharmacy setting. Methods:We conducted a cross-sectional survey in rural/urban community pharmacies with adult noncancer patients. The survey included validated measures for opioid medication misuse risk, drug and alcohol use, and physical and mental health problems. Descriptive statistics were calculated, and bivariate and multivariable logistic regression evaluated relationships between opioid medication misuse risk and patient demographics, behavioral, mental, and physical health. Results:A total of 164 patients completed the survey (87% response rate), revealing positive screens for prescription opioid misuse risk (14.3%), illicit drug use (7.3%), hazardous alcohol use (21.4%), depression (25.8%), and posttraumatic stress disorder (PTSD; 17.1%). Bivariate analyses revealed increased odds of a positive opioid medication misuse risk score with a positive screen for illicit drug use in the previous year (odds ratio = 3.91; 95% confidence interval [CI], 1.05–14.63) and PTSD (odds ratio = 6.7; 95% CI, 2.54–17.69). In adjusted multivariable analyses, these relationships strengthened such that a positive screen for illicit drug use (adjusted odds ratio = 12.96; 95% CI, 2.18–76.9) and PTSD (adjusted odds ratio = 13.3; 95% CI, 3.48–50.66) increased odds for a positive opioid medication misuse risk score. Conclusions:Findings confirmed the feasibility of screening risk factors and positive opioid medication misuse risk among community pharmacy patients. Future research should validate these findings as a foundation to intervention development.
Purification and Characterization of a New Eukaryotic Protein Translation Factor

A new protein with translational activity has been identified on the basis of its ability to stimulate translation in an in vitro globin synthesis assay deficient in eukaryotic initiation factor (eIF) 4B and eIF4F. This protein has been purified to greater than 80% homogeneity from rabbit reticulocyte lysate and has been given the name eIF4H. eIF4H was shown to stimulate the in vitro activities of eIF4B and eIF4F in globin synthesis, as well as the in vitro RNA-dependent ATPase activities of eIF4A, eIF4B, and eIF4F. Three tryptic fragments of eIF4H yielded amino acid sequences that were 100% identical to a human sequence found in the GeneBankTM that codes for a previously uncharacterized protein (HUMORFU_1). The calculated molecular weight of the protein encoded by this sequence, its predicted cyanogen bromide fragmentation, and calculated isoelectric point are all consistent with those determined experimentally for eIF4H. Also, the presence of an RNA recognition motif within HUMORFU_1 suggests that eIF4H may interact with mRNA. We conclude that this newly characterized protein, eIF4H, functions to stimulate the initiation of protein synthesis at the level of mRNA utilization, and is encoded by the gene for HUMORFU_1.
Effect of maternal and postweaning folic acid supplementation on global and gene-specific DNA methylation in the liver of the rat offspring.

SCOPE Intrauterine and early-life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use, and periconceptional supplementation. We investigated the effect of maternal and postweaning folic acid supplementation on DNA methylation in the rat offspring. METHODS AND RESULTS Female rats were placed on a control or folic acid-supplemented diet during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or supplemented diet for 11 weeks. At weaning, maternal folic acid supplementation significantly decreased global (p < 0.001) and site-specific DNA methylation of the Ppar-γ, ER-α, p53, and Apc genes (p < 0.05) in the liver. At 14 weeks of age, postweaning, but not maternal, folic acid supplementation significantly decreased global DNA methylation (p < 0.05). At 14 weeks of age, both maternal and postweaning folic acid supplementation significantly increased DNA methylation of the Ppar-γ, p53, and p16 genes (p < 0.05) whereas only postweaning FA supplementation significantly increased DNA methylation of the ER-α and Apc genes (p < 0.05). CONCLUSION Our data suggest that maternal and postweaning folic acid supplementation can significantly modulate global and gene-specific DNA methylation in the rat offspring. The functional ramifications of the observed DNA methylation changes need to be determined in future studies.
Mitochondria inheritance is a key factor for tolerance to dehydration in wine yeast production

Mitochondria are the cell's powerhouse when organisms are grown in the presence of oxygen. They are also the source of reactive oxygen species that cause damage to the biochemical components of the cell and lead to cellular ageing and death. Under winemaking conditions, Saccharomyces yeasts exclusively have a fermentative metabolism due to the high sugar content of grape must. However, their production as an active dry yeast (ADY) form required aerobic propagation and a dehydration process. In these industrial steps, oxidative stress is particularly harmful for the cell. In this work, we analysed the impact of the mitochondrial genome on oxidative stress response, longevity and dehydration tolerance using the synthetic interspecific hybrids obtained between two S. cerevisiae and S. uvarum strains. The isogenic nature of nuclear DNA of such hybrids allowed us to analyse the impact of mitochondrial DNA for fermentative and oxidative stress conditions. Under grape must conditions, the inheritance of mitochondrial DNA poorly impacted the fermentative performance of interspecific hybrids, unlike the hybrids with S. cerevisiae mitochondrial inheritance, which displayed increased tolerance to oxidative stress and dehydration, and showed an extended chronological longevity when cells were grown with aeration.
Activator Protein-1 Regulation of Murine Aldehyde Dehydrogenase 1a1

Previously we demonstrated that aldehyde dehydrogenase (ALDH) 1a1 is the major ALDH expressed in mouse liver and is an effective catalyst in metabolism of lipid aldehydes. Quantitative real-time polymerase chain reaction analysis revealed a ≈2.5- to 3-fold induction of the hepatic ALDH1A1 mRNA in mice administered either acrolein (5 mg/kg acrolein p.o.) or butylated hydroxylanisole (BHA) (0.45% in the diet) and of cytosolic NAD+-dependent ALDH activity. We observed ≈2-fold increases in ALDH1A1 mRNA levels in both Nrf2(+/+) and Nrf2(−/−) mice treated with BHA compared with controls, suggesting that BHA-induced expression is independent of nuclear factor E2-related factor 2 (Nrf2). The levels of activator protein-1 (AP-1) mRNA and protein, as well as the amount of phosphorylated c-Jun were significantly increased in mouse liver or Hepa1c1c7 cells treated with either BHA or acrolein. With use of luciferase reporters containing the 5′-flanking sequence of Aldh1a1 (−1963/+27), overexpression of c-Jun resulted in an ≈4-fold induction in luciferase activity, suggesting that c-Jun transactivates the Aldh1a1 promoter as a homodimer and not as a c-Jun/c-Fos heterodimer. Promoter deletion and mutagenesis analyses demonstrated that the AP-1 site at position −758 and possibly −1069 relative to the transcription start site was responsible for c-Jun-mediated transactivation. Electrophoretic mobility shift assay analysis with antibodies against c-Jun and c-Fos showed that c-Jun binds to the proximal AP-1 site at position −758 but not at −1069. Recruitment of c-Jun to this proximal AP-1 site by BHA was confirmed by chromatin immunoprecipitation analysis, indicating that recruitment of c-Jun to the mouse Aldh1a1 gene promoter results in increased transcription. This mode of regulation of an ALDH has not been described before.
Increased brain injury and vascular leakage after pretreatment with p38‐inhibitor SB203580 in transient ischemia

Objectives – Focal cerebral ischemia activates intracellular signaling pathways including the mitogen‐activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38‐inhibitor SB203580 on infarct size and blood–brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI).
Performance on the Adult Rheumatology In‐Training Examination and Relationship to Outcomes on the Rheumatology Certification Examination

The American College of Rheumatology (ACR) Adult Rheumatology In‐Training Examination (ITE) is a feedback tool designed to identify strengths and weaknesses in the content knowledge of individual fellows‐in‐training and the training program curricula. We determined whether scores on the ACR ITE, as well as scores on other major standardized medical examinations and competency‐based ratings, could be used to predict performance on the American Board of Internal Medicine (ABIM) Rheumatology Certification Examination.
Thermal, electrical characteristics and morphology of poly(Ethylene-Co-Ethyl Acrylate)/CNT nanocomposites

In this study, nanocomposites with binary elements of poly (ethylene-co-ethyl acrylate)/carbon nanotube (EEA/CNT) were prepared so that their thermal and electrical characteristics and morphology, not reported in any literature, could be measured. For the thermal characteristics, their thermal degradation and activation energy were measured by using the thermogram (TG) curve, which was obtained by a heating from 100deg C to 600degC with a thermogravimetric analysis (TGA). In addition, after maintaining a thermal equilibrium at each temperature of 25degC, 50degC, 75degC, 100degC, 125degC and 150degC, their thermoluminescence was measured for 20 minutes. Then, the volume resistivity of EEA/CNT was measured by means of ASTM D991. Morphology of EEA/CNT was measured at 15 kV. First, with the TGA experiments, the thermal degradation temperatures of the specimens containing a CNT were found to shift to a higher temperature region, while activation energy values between 204 kJ/mol and 213 kJ/mol were obtained. Secondly, with the thermoluminescence experiment, the specimens containing a CNT were found to show a much smaller thermoluminescence than the specimens without a CNT. Thirdly, the volume resistivity was lowered as the CNT content increased, which is not enough to create a semiconductivity. This is thought to reveal that the melting blend method has a worse dispersibility than the solution method. Lastly, with the measurements of the fractured surfaces from the field emission scanning electron microscope (FESEM) experiment, it was observed that the CNT was dispersed in the form of many lumps as its content increased.
Revised age estimates of Australopithecus-bearing deposits at Sterkfontein, South Africa.

The Sterkfontein fossil site in South Africa has produced the largest concentration of early hominin fossils from a single locality. Recent reports suggest that Australopithecus from this site is found within a broad paleontological age of between 2.5-3.5 Ma (Partridge [2000] The Cenozoic of Southern Africa, Oxford: Oxford Monographs, p. 100-125; Partridge et al. [2000a], The Cenozoic of Southern Africa, Oxford: Oxford Monographs, p. 129-130; Kuman and Clarke [2000] J Hum Evol 38:827-847). Specifically, the hominin fossil commonly referred to as the "Little Foot" skeleton from Member 2, which is arguably the most complete early hominin skeleton yet discovered, has been magnetostratigraphically dated to 3.30-3.33 Ma (Partridge [2000] The Cenozoic of Southern Africa, Oxford: Oxford Monographs, p. 100-125; Partridge et al. [2000a], The Cenozoic of Southern Africa, Oxford: Oxford Monographs, p. 129-130). More recent claims suggest that hominin fossils from the Jacovec Cavern are even older, being dated to approximately 3.5 Ma. Our interpretation of the fauna, the archeometric results, and the magnetostratigraphy of Sterkfontein indicate that it is unlikely that any Members yet described from Sterkfontein are in excess of 3.04 Ma in age. We estimate that Member 2, including the Little Foot skeleton, is younger than 3.0 Ma, and that Member 4, previously dated to between 2.4-2.8 Ma, is more likely to fall between 1.5-2.5 Ma. Our results suggest that Australopithecus africanus should not be considered as a temporal contemporary of Australopithecus afarensis, Australopithecus bahrelghazali, and Kenyanthropus platyops.
Message Transmission Efficiency Through Five Telecommunication Technologies for Signing Deaf Users

ABSTRACT This cross-sectional research design compares the efficiency of videoconferencing in distance communication for signing deaf persons with that of teletypewriter (TTY)-based telecommunication for the deaf. The efficiency of message transmission was evaluated among 30 signing deaf persons (18 to 65 years) under the six following experimental conditions: (a) Omnitor Allan eC software, (b) Polycom ViaVideo II software, (c) Microsoft Windows Live Messenger software, (d) the D-Link videophone, (e) TTY (written French), and (f) face to face (reference standard). Three timed intelligibility tests and a satisfaction assessment were carried out for each of the experimental conditions. Results showed that videoconferencing technologies offer a better efficacy/time ratio for communication than does TTY. Communication using videoconferencing technologies was very similar to face-to-face communication; this was also true for technologies that are not designed specifically for the deaf population. Equivalent satisfaction levels were observed between TTY and videoconferencing technologies. Microsoft Windows Live Messenger was less preferred due to image fluidity issues.
Degradation of Amyotrophic Lateral Sclerosis-linked Mutant Cu,Zn-Superoxide Dismutase Proteins by Macroautophagy and the Proteasome*

Mutations in the Cu,Zn-superoxide dismutase (SOD1) gene cause ∼20% of familial cases of amyotrophic lateral sclerosis (fALS). Accumulating evidence indicates that a gain of toxic function of mutant SOD1 proteins is the cause of the disease. It has also been shown that the ubiquitin-proteasome pathway plays a role in the clearance and toxicity of mutant SOD1. In this study, we investigated the degradation pathways of wild-type and mutant SOD1 in neuronal and nonneuronal cells. We provide here the first evidence that wild-type and mutant SOD1 are degraded by macroautophagy as well as by the proteasome. Based on experiments with inhibitors of these degradation pathways, the contribution of macroautophagy to mutant SOD1 clearance is comparable with that of the proteasome pathway. Using assays that measure cell viability and cell death, we observed that under conditions where expression of mutant SOD1 alone does not induce toxicity, macroautophagy inhibition induced mutant SOD1-mediated cell death, indicating that macroautophagy reduces the toxicity of mutant SOD1 proteins. We therefore propose that both macroautophagy and the proteasome are important for the reduction of mutant SOD1-mediated neurotoxicity in fALS. Inhibition of macroautophagy also increased SOD1 levels in detergent-soluble and -insoluble fractions, suggesting that both detergent-soluble and -insoluble SOD1 are degraded by macroautophagy. These findings may provide further insights into the mechanisms of pathogenesis of fALS.
The generation of immunogenic peptides can be selectively increased or decreased by proteolytic enzyme inhibitors.

The ability of splenic APC and a B cell hybridoma (LS.102.9) to process and present OVA to a panel of T-T hybridomas with different fine specificities was investigated. Splenic APC process and present OVA to all the T-T hybrids. The B cell hybridoma could similarly process and present OVA to some T-T hybrids but was very inefficient in stimulating two of the T cell hybridomas. The presentation of native OVA to these two T-T hybrids was significantly increased by leupeptin. Pulsing experiments demonstrated that leupeptin acted on the APC at a step before the processed Ag was displayed on the cell surface in association with MHC molecules. Leupeptin has no effect on the presentation of OVA peptides by LS.102. 9 to the T-T hybrids. Leupeptin inhibits the generation of the epitopes of OVA that LS.102. 9 produces under basal conditions. We also surveyed the effect of other protease inhibitors and observed similar augmenting and inhibitory effects on the presentation of selected OVA epitopes. The augmentation of processing by a protease inhibitor indicates that in the lysosomal/endosomal compartment proteases have capacity to both generate and destroy immunogenic peptides. Our data suggest that protease inhibitors could potentially be used as immunomodulators and are discussed in terms of physiology of the lysosomal/endosomal compartment.
Quality of community-based day centre services for people with psychiatric disabilities: psychometric properties of the Quality in Psychiatric Care – Daily Activities (QPC–DA)

Abstract Background/aims The aim of the present study was to test the psychometric properties and dimensionality of the instrument Quality in Psychiatric Care – Daily Activities (QPC–DA) and to briefly describe the day centre attendees’ perception of the quality at community-based day centre services. Methods A sample of 218 attendees from 14 community-based day centre services in seven municipalities in Sweden participated in the study. Results Confirmatory factor analysis revealed that the QPC–DA consists of six dimensions and has a factor structure that to a large extent corresponds to that found in other studies of quality in psychiatric care settings, such as inpatient, outpatient, forensic inpatient, and housing support for people with psychiatric disabilities. The internal consistency of the factors was satisfactory and thus the QPC–DA showed adequate psychometric properties. The attendees’ ratings of quality of community-based day centre services were generally high. The highest rating was for the encounter dimension and the lowest for the participation and the secluded environment dimensions, indicating areas for improvement. Conclusion/significance The QPC–DA includes important aspects of the attendees’ assessment of quality of community-based day centre services and offers a simple and inexpensive way to evaluate quality from their perspective.
A Randomized Controlled Trial of Fractional Laser Therapy and Dermabrasion for Scar Resurfacing

Background Dermabrasion has been the standard resurfacing procedure for postsurgical scars, but recovery can be long. Fractionated carbon dioxide (CO2) laser is a safe, effective tissue resurfacing modality, but no prospective trial has compared its safety or efficacy with that of dermabrasion for postsurgical scar resurfacing. Objective To compare the safety and efficacy of single‐treatment fractional photothermolysis with that of single‐treatment dermabrasion for postsurgical scar resurfacing on the face. Methods and Materials A split‐scar method was used to compare fractionated CO2 laser and diamond fraise dermabrasion on postsurgical scars of the face. Primary endpoint was safety at day 0, 1 week, and 1 month. Secondary endpoint was efficacy at 3 months as measured by blinded evaluation of standardized photographs. Results Safety data revealed that there was less erythema (p = .001) and bleeding (p = .001) at day 0, less erythema (p = .01) and edema (p = .046) at 1 week, and a trend toward less erythema at 1 month (p = .06) with fractionated CO2. Efficacy data at 3 months revealed equivalent scar improvements (p = .77). Conclusion Fractionated CO2 laser therapy should be considered a safe alternative for surgical scar resurfacing on the face. The safety profile exceeds that of dermabrasion, and it has a quicker clinical recovery and equivalent cosmetic efficacy.