Miracle-dz/UniFAR-FTUs huggingface dataset:
Early anemia and rapid virological response improve the predictive efficiency of IL28B‐genotype for treatment outcome to antiviral combination therapy in patients infected with chronic HCV genotype 1

IL28B genotypes and virological response within 4 weeks are predictors of sustained virological response in patients infected with chronic hepatitis C virus (HCV) genotype 1 treated with antiviral dual combination therapy. The predictive value of “early” anemia (within 4 weeks) alone or in combination with the two other predictors has not been studied yet. A total of 305 pegylated interferon‐α and ribavirin‐treated patients with HCV genotype 1 were included in this study. Hemoglobin values at week 0, 4, 8, and 12 as well as the predictive efficiency of early anemia (hemoglobin value below the gender‐specific lower limit: female < 11.5; male < 13.5 g/dl) during therapy were assessed with IL28B genotypes and rapid virological response. Forty‐eight percent of treated patients developed early anemia. In both females and males (64%), a decrease of hemoglobin concentration of 3 g/dl (female: 14.7 ± 1.1 to 11.4 ± 1.3; male: 15.2 ± 1.2 to 12.2 ± 1.5) significantly correlated with sustained virological response. 64% of IL28B‐CC patients showed a sustained virological response. Seventy‐eight percent of patients with rapid virological response definitively eliminated the virus. Early anemia (81:48:41%) and rapid virological response (83:91:92%) increased the predictive efficiency of IL28B rs12979860 genotype distribution (CC:CT:TT). IL28B‐CC and early anemia as well as IL28B‐CC and rapid virological response had an Odds ratio of 42.4 or 75 to achieve a sustained virological response compared to TT without early anemia or rapid virological response. This finding may help to early identify responders to standard PEG‐IFN‐α and ribavirin treatment even within those with unfavorable IL28B genotype. J. Med. Virol. 84: 1208–1216, 2012. © 2012 Wiley Periodicals, Inc.
Nuclear Factor-Kappa B Mediates One-Lung Ventilation-Induced Acute Lung Injury in Rabbits

ABSTRACT Introduction: Several studies have revealed the adverse effect of one-lung ventilation (OLV) on pulmonary function. Nuclear factor-kappa B (NF-κB) is a principal transcription factor of proinflammatory genes. This study was designed to investigate the role of NF-κB in OLV-mediated lung injury. Methods: Male rabbits, weighing 2.2 ± 0.3 kg, were randomly divided into five groups: sham tracheostomized (Sham), OLV (VT = 10 ml/kg, FiO2 = 1.0), two-lung ventilation (TLV, VT = 10 ml/kg, FiO2 = 1.0), OLV preceded by the treatment with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC, 50 mg/kg, i.v.), and TLV with the PDTC pretreatment. Arterial blood gases, lung pathological changes, and production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-8) were assessed. NF-κB activation was determined by electrophoretic mobility shift assay (EMSA) and western blotting of nuclear NF-κB p65. Results: The OLV significantly decreased the ratio of partial pressure of oxygen and fraction inspired oxygen (PaO2/FiO2) compared to the Sham group (p < .01). However, the TLV had no evident effect on the PaO2/FiO2 ratio. The pretreatment with PDTC significantly reversed the OLV-induced reduction in the PaO2/FiO2 ratio. The PDTC pretreatment also markedly attenuated the OLV-mediated lung injury and proinflammatory cytokine production. The OLV potentiated the NF-κB DNA binding activity assessed by EMSA and the NF-κB nuclear translocation. The OLV-mediated NF-κB activation was markedly inhibited by the PDTC pretreatment. Conclusion: Our data collectively demonstrate that OLV can cause lung injury through the activation of NF-κB and the production of proinflammatory cytokines. Blocking NF-κB reduces lung inflammation and may be an effective strategy in the management of OLV-induced lung damage.
HIV antigen‐induced release of histamine from basophils from HIV infected patients

Basophil leukocytes from 39 HIV‐infected patients with various degrees of immunodeficiency and disease progression were stimulated with an HIV antigen preparation. Cells from 19 of 22 patients with AIDS and all of six patients with milder degrees of HXV‐related disease showed significant histamine release. In contrast, cells from 11 asymptomatic HIV‐infected patients and 11 healthy control persons released no histamine. The histamine release induced by HIV antigen was found to be inversely correlated to the number of CD4 positive T lymphocytes. These results indicate that the histamine release was related to both the clinical stage of disease and the degree of immunodeficiency. Passive sensitization experiments showed that IgE, but not IgG, was reponsible for the induction of histamine release, indicating the reaction to be type 1 allergic. The histamine release caused by HIV might be involved in the development of disease because of the immunomodulating properties of this mediator.
Prevalence and burden of self-reported blindness, low vision, and visual impairment in the French community: a nationwide survey.

OBJECTIVE To estimate the prevalence of self-reported visual impairment and its association with disabilities, handicaps, and socioeconomic consequences. METHODS A national survey was conducted on a random stratified sample of 359 010 French citizens living in the community; 21 760 subjects were selected at random and 16 945 persons (78%) agreed to further questioning. Four thousand ninety-one randomly selected caregivers were interviewed. Four subgroups of subjects were defined (blind or light perception only, low vision or still have form perception, other visual problems, and no visual problems). These were compared after adjustment for age, comorbidity, and household size differences. RESULTS The prevalence of blindness was 0.10% and of low vision, 1.94%. Subjects with blindness needed assistance with daily activities more often than subjects with no visual problems; they also needed more house modifications. Many subjects with blindness (46.8%) and subjects with low vision (29.0%) were registered for social allowances. Subjects with blindness had fewer paid activities (4.5%) than subjects with no visual problems (20.7%). Social allowances increased considerably (by 277) between those with low vision and those with blindness. Monthly household incomes were lower (P<.001) for subjects with low vision (1255) and blindness (1587) than for subjects with no visual problems (1851). MAIN OUTCOME MEASURES Collected data included social demography, home description, household income, handicaps, disabilities, social allowances, and daily activities. CONCLUSION The results demonstrate associations between self-reported visual impairment and daily living.
Lymphedema in tuberous sclerosis complex

Congenital lymphedema has been described as a possible rare association of tuberous sclerosis complex (TSC), with only six previous cases reported in the literature. TSC is an autosomal dominant, multisystem disorder connected to aberrant regulation of the mammalian target of rapamycin (mTOR) pathway. The aim of this study is to review cases of lymphedema in a large cohort of TSC patients. The medical records of 268 patients seen at The Herscot Center for Children and Adults with Tuberous Sclerosis Complex at the Massachusetts General Hospital from 2002 to 2012 were retrospectively reviewed for reports of lymphedema or edema of unknown etiology. Genotypic and phenotypic data were collected in accordance with institutional review board (IRB) approval. This cohort presents two new cases of congenital lymphedema in TSC patients and acquired lymphedema was found in eight additional cases. Thus, we report 10 new cases of lymphedema in TSC (4%). The two patients with congenital lymphedema were female, as were the previous six reported cases. The frequency of lymphedema reported here (4%) is higher than the estimated prevalence in the general population (0.133–0.144%), suggesting a higher frequency of lymphedema in TSC. This study shows that patients with TSC and lymphedema are more likely to be females with renal AMLs and suggests that congenital lymphedema is a gender‐specific (female) manifestation of TSC. Exploration of the potential role of mTOR antagonists may be important in treatment of lymphedema in TSC patients. © 2014 Wiley Periodicals, Inc.
Frequency of Seborrheic Keratosis Biopsies in the United States: A Benchmark of Skin Lesion Care Quality and Cost Effectiveness

BACKGROUND Most seborrheic keratoses may be readily clinically differentiated from skin cancer, but occasional lesions resemble atypical melanocytic neoplasms. OBJECTIVE To evaluate the frequency, cost, and intensity of procedures performed that result in the removal and histopathologic evaluation of seborrheic keratoses. METHODS Episodes of surgical removal of lesions that were identified as seborrheic keratoses by histologic identification were determined using Medicare Current Beneficiary Survey data from 1998 to 1999. These episodes were defined by a histopathology procedure code that is associated with a diagnosis code for seborrheic keratosis. We then identified what procedure(s) generated the histopathology specimen. Biopsy and shave procedures were considered “low intensity,” whereas excision and repair procedures were considered “high intensity. ” RESULTS Dermatologists managed 85% of all episodes of seborrheic keratoses. Dermatologists managed 89% of seborrheic keratosis episodes using low-intensity procedures compared with 51% by other specialties. For nondermatologists, 46% of the treatment cost ($9 million) to Medicare was generated from high-intensity management compared with 15% by dermatologists ($6 million). CONCLUSION There is a significant difference in the management of suspicious pigmented lesions between dermatologists and other specialists. This affects both the cost and quality of care.
Research on novel flexible pneumatic actuator FPA

A novel flexible pneumatic actuator FPA is proposed in this paper. The structure and properties of FPA are described. Based on FPA, flexible pneumatic bending joint, flexible pneumatic torsion joint and flexible pneumatic spherical joint are developed. The mathematical models of flexible pneumatic bending joint and flexible pneumatic spherical joint are established. Experiments are carried out to investigate the characteristics of these two joints by utilizing intelligent control techniques. Experimental results demonstrate that flexible pneumatic bending joint and flexible pneumatic spherical joint can meet the designed requirement of application. Finally, the aim and direction of the future work are forecasted.
Discovery of a water vapor layer in the Arctic summer mesosphere: Implications for polar mesospheric clouds

We report the discovery of a layer of enhanced water vapor in the Arctic summer mesosphere that was made utilizing two new techniques for remotely determining water vapor abundances. The first utilizes Middle Atmosphere High Resolution Spectrograph Investigation (MAHRSI) OH measurements as a proxy for water vapor. The second is a reanalysis of Halogen Occultation Experiment (HALOE) water vapor data with a technique to simultaneously determine polar mesospheric cloud (PMC) ice particle extinction along with the water vapor abundance. These results reveal a narrow layer of enhanced water vapor centered between 82–84 km altitude and coincident with PMCs, that exhibits water vapor mixing ratios of 10–15 ppmv. This indicates that a higher degree of supersaturation is present in the PMC region, and that PMCs are thus more efficient at sequestering total water (both ice particles and vapor) within the layer, than previously believed.
Evaluation of multiple primary and combination screening strategies in postmenopausal women for detection of cervical cancer in China

As China's population ages, the importance of determining prevalence of cervical disease and accurate cervical cancer screening strategies for postmenopausal women is increasing. Seventeen population‐based studies were analyzed to determine prevalence of cervical neoplasia in postmenopausal women. All women underwent HPV DNA testing, visual inspection with acetic acid (VIA) and cytology testing. Diagnostic values for primary and combinations screening methods included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate and area under curve (AUC) were calculated using directed biopsy or four quadrants biopsy as reference standard. Premenopausal and postmenopausal women had equal HPV infection and cervical neoplasia rates (p > 0.05). HPV DNA testing CIN3+ sensitivity, specificity, PPV, NPV, referral rate and AUC were 97.9% (95% CI: 90.2–99.9%), 84.2% (95% CI: 82.8–85.5%), 9.9% (95% CI: 7.4–12.8%), 100% (95% CI: 99.8–100%), 17.2% (95% CI: 15.9–18.7%), 0.911, respectively. VIA values were 41.7% (95% CI: 28.4–55.9%), 94.5% (95% CI: 93.6–95.3%), 11.8% (95% CI: 7.5–17.3%), 98.9% (95% CI: 98.5–99.3%), 6.2% (95% CI: 5.3–7.1%) and 0.681, respectively. Values for VIA with HPV triage were 39.6% (95% CI: 26.6–53.8%), 99.2% (95% CI: 98.8–99.5%), 45.2% (95% CI: 30.8–60.4%), 98.9% (95% CI: 98.5–99.3%), 1.5% (95% CI: 1.1–2.0%) and 0.694, respectively. VIA and HPV DNA co‐test values were 100% (95% CI: 94.0–100%), 79.5% (95% CI: 78.0–81.0%), 8.0% (95% CI: 6.0–10.3%), 100% (95% CI: 99.9–100%), 21.9% (95% CI: 20.4–23.4%) and 0.898, respectively. VIA sensitivity decreases significantly in postmenopausal women compared to premenopausal performance. HPV DNA testing maintains performance between pre‐ and postmenopausal women and is the most accurate primary modality for screening postmenopausal populations in low resource areas of China.
Fractional integration and cointegration in merger and acquisitions in the US petroleum industry

ABSTRACT This article employs methodologies based on fractional integration and cointegration to analyse the time-series properties of merger and acquisitions (M&A) activity and crude oil prices in the US from 1980 to 2012. Our results indicate that an increase in the crude oil price produces a significant increase in the M&A data between 2 and 3 months after the initial shock.
Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells

Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d−/− mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d−/− retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx.
Metastatic germ cell tumors: modeling for response to chemotherapy.

PURPOSE This study sought to determine factors that predict response to chemotherapy for patients with advanced germ cell tumors (GCTs), to evaluate different methods by which serum tumor markers can be used to predict response independent of assay method, and to develop criteria to guide allocation to clinical trials. METHODS Pretreatment data from 796 patients treated with platinum-based chemotherapy on Memorial Hospital protocols from 1975 to 1990 were analyzed. Multivariate analyses were performed on a developmental data set (n = 597) to assess for independently significant predictors of response. Predictive models developed using these methods were confirmed on the validation set (n = 199). RESULTS Independently significant factors for response included a mediastinal primary tumor (.015), pure seminomatous histology (.002), metastases to nonpulmonary visceral sites (bone, liver, and brain; .0001), and the pretreatment values of lactate dehydrogenase (LDH; .0001) and human chorionic gonadotropin (HCG; .0001). The likelihood of complete response (CR) was increased by seminomatous histology and decreased by the other factors. Serum levels of HCG and LDH could predict outcome independent of assay methodology. A model to predict good-, intermediate-, and poor-risk categories with CR rates of 92%, 76%, and 39%, respectively, was developed. CONCLUSION The independent prognostic factors of serum tumor markers LDH and HCG, the sites of metastases, and the primary origin of GCTs can predict outcome in patients with advanced GCT. These factors should be considered in the allocation of patients with advanced disease to clinical trials and have been included in the new tumor-node-metastasis (TNM) staging systems developed for the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).
Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women.

OBJECTIVE To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus. DESIGN Cohort study. SETTING In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load. MAIN OUTCOME MEASURE Non-insulin-dependent diabetes mellitus. RESULTS During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes.
Quantification of growth factors by using a new system for obtaining platelet-rich plasma.

OBJECTIVE To verify the performance of a new method for obtaining platelet-rich plasma, while avoiding contamination of the sample during its processing. STUDY DESIGN Twenty healthy patients were selected, from whom 21 ml of blood was extracted. We then proceeded to study the platelets and growth factors in basal blood after centrifuging the sample by using a new closed system for obtaining platelet-rich plasma (PRP). RESULTS After centrifuging the blood sample, double the amount of platelets as that found in basal blood was obtained. Of the four growth factors analyzed, only the factor similar to insulin (IGF) contained the same concentration after the centrifuge process. The platelet-derived growth factor (PDGF) and the vascular growth factor (VGF) were multiplied by six with respect to the basal values and disproportionately increased the levels of the transforming growth factor β (TGF-β). CONCLUSIONS The new closed method for obtaining PRP, after avoiding contamination of the sample following its use, offers levels of platelet concentrate and growth factors necessary for regeneration.
A Histone Acetyltransferase Regulates Active DNA Demethylation in Arabidopsis

To Silence or Not to Silence Repressed genes commonly have methylated DNA, and/or covalent histone modifications associated with silent chromatin, and/or associated small interfering (si)RNAs. All three features are components of gene-silencing systems (see the Perspective by Jacob and Martienssen). In a screen for components of DNA methylation gene-silencing systems in the flowering plant, Moissiard et al. (p. 1448, published online 3 May) identified the genes AtMoRC1 and AtMORC6, which are homologs of the mouse Microrchidia1 gene. AtMORC1 and AtMORC6 are involved in silencing transposable elements and genes corresponding to DNA-methylated loci, and yet neither gene is required for maintenance of DNA methylation. Instead, AtMoRC1 and AtMORC6 are related to proteins that remodel chromatin superstructure, and they seem to control gene-silencing through the higher-order compaction of methylated and silent chromatin. Qian et al. (p. 1445) identified an Arabidopsis gene, IDM1 (increased DNA methylation 1), that is involved in regulating DNA methylation at loci enriched for repeats and multigene families containing highly homologous genes. IDM1 protects target genes from DNA silencing and recognizes both histone H3 and methylated DNA at target loci and is able to acetylate histone H3. A plant epigenetic regulator recognizes both histones and methylated DNA and prevents gene silencing. Active DNA demethylation is an important part of epigenetic regulation in plants and animals. How active DNA demethylation is regulated and its relationship with histone modification patterns are unclear. Here, we report the discovery of IDM1, a regulator of DNA demethylation in Arabidopsis. IDM1 is required for preventing DNA hypermethylation of highly homologous multicopy genes and other repetitive sequences that are normally targeted for active DNA demethylation by Repressor of Silencing 1 and related 5-methylcytosine DNA glycosylases. IDM1 binds methylated DNA at chromatin sites lacking histone H3K4 di- or trimethylation and acetylates H3 to create a chromatin environment permissible for 5-methylcytosine DNA glycosylases to function. Our study reveals how some genes are indicated by multiple epigenetic marks for active DNA demethylation and protection from silencing.