Miracle-dz/UniFAR-FTUs huggingface dataset:
IPA: Integrated predictive gene signature from gene expression based breast cancer patient samples

Background: Novel predictive markers are needed to accurately diagnose the breast cancer patients so they do not need to undergo any unnecessary aggressive therapies. Various gene expression studies based predictive gene signatureshave generated in the recent past to predict the binary estrogen-receptor subclass or to predict the therapy response subclass. However, the existing algorithms comes with many limitations, including low predictive performances over multiple cohorts of patients and non-significant or limited biological roles associated with thepredictive gene signatures. Therefore, the aim of this study is to develop novel predictive markers with improved performances.Methods: We propose a novel prediction algorithm called IPA to construct a predictive gene signature for performing multiple prediction tasks of predicting estrogen-receptor based binary subclass and predicting chemotherapy response (neoadjuvantly) based binary subclass. The constructed gene signature with considering multiple classification techniques was used to evaluate the algorithm performance on multiple cohorts of breast cancer patients.Results: The evaluation on multiple validation cohorts demonstrated that proposed algorithm achieved stable and high performance to perform prediction tasks, with consideration given to any classification techniques. We show that the predictive gene signature of our proposed algorithm reflects the mechanisms underlying the estrogen-receptors or response to therapy with significant greater biological interpretations, compared with the other existing algorithm.
Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients.

AIM To assess the efficacy and safety of combined pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) infection in renal transplant recipients. METHODS This is a retrospective chart review of post renal transplant patients who were positive for anti-HCV and HCV-RNA, and who have received treatment with combination of pegylated interferon and ribavirin between October 2003 and December 2008. Only patients with stable graft function and absence of evidence of cirrhosis and who received the therapy for continuous 48 wk were included. Nineteen patients (13 male and 6 female) were identified and included. The patient's complete blood count, liver and kidney profile, and calculated glomerular filtration rate (GFR) were monitored every 6-8 wk while on treatment. HCV-RNA was tested at 12 wk for early virological response, at 48 wk for end of treatment response (ETR), and then retested at 24, and 48 wk after completion of therapy for sustained virological response (SVR). Liver biopsies were obtained before treatment from all patients and graft kidney biopsies were performed as required. RESULTS Of the entire cohort, 9 patients (47.4%) showed an ETR and 8 had SVR (42.1%). Of the 8 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 78.9% had their ALT normalized (including the virological non responders). ALT was normal in all responders at the end of therapy and at 24 wk post therapy (100%). Only one patient (5.3%) developed an increase in creatinine and decline in GFR from baseline towards the end of treatment. This patient's kidney biopsy revealed borderline rejection. There was no impact on response by HCV-genotype, initial HCV RNA load, age or sex of the patient or duration post transplant before commencement of therapy. All patients tolerated treatment in the same way as non-transplant with no unusual or increased occurrence of side effects. CONCLUSION The combination of pegylated interferon and ribavirin is effective in suppressing HCV-RNA, with a low risk of graft rejection or failure in HCV infected renal transplant recipients.
Concurrent thalidomide and radiation therapy for extensive arterio-venous malformations

e report on a patient with extensive cervical, thoracic and left arm arterio-venous malformations (AVM) who had extensive growth of the AVM after prior embolization and surgical ligation, and who responded dramatically after concurrent radiation and thalidomide therapy. His clinical course suggests that local up-regulation of angiogenesis plays an important role in the pathogenesis of AVM.
Influence of aging on peripheral nerve function and regeneration

Abstract Aging deeply influences several morphologic and functional features of the peripheral nervous system (PNS). Morphologic studies have reported a loss of myelinated and unmyelinated nerve fibers in elderly subjects, and several abnormalities involving myelinated fibers, such as demyelination, remyelination and myelin balloon figures. The deterioration of myelin sheaths during aging may be due to a decrease in the expression of the major myelin proteins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytoskeletal proteins in the peripheral nerve. Aging also affects functional and electrophysiologic properties of the PNS, including a decline in nerve conduction velocity, muscle strength, sensory discrimination, autonomic responses, and endoneurial blood flow. The age‐related decline in nerve regeneration after injury may be attributed to changes in neuronal, axonal, Schwann cell and macrophage responses. After injury, Wallerian degeneration is delayed in aged animals, with myelin remnants accumulated in the macrophages being larger than in young animals. The interaction between Schwann cells and regenerative axons takes longer, and the amount of trophic and tropic factors secreted by reactive Schwann cells and target organs are lower in older subjects than they are in younger subjects. The rate of axonal regeneration becomes slower and the density of regenerating axons decrease in aged animals. Aging also determines a reduction in terminal and collateral sprouting of regenerated fibers, further limiting the capabilities for target reinnervation and functional restitution. These age‐related changes are not linearly progressive with age; the capabilities for axonal regeneration and reinnervation are maintained throughout life, but tend to be delayed and less effective with aging.
Analysis of laboratory data in acne patients treated with isotretinoin: is there really a need to perform routine laboratory tests?

INTRODUCTION: Isotretinoin has been used to treat acne since 1982. Its current indications in the package insert are limited and many physicians still feel uncomfortable prescribing it because of its side effects. Serum levels of liver enzymes and lipids are carried out as a routine in most clinics both before and during treatment. AIMS: Our objective was to evaluate the effect of isotretinoin on serum lipids, liver function and other laboratory parameters in order to assess the necessity to perform routine laboratory tests. METHODS: Computerized medical files of 1292 patients in private practice that received isotretinoin for acne were analyzed. RESULTS: 907 patients completed a treatment course of 5 to 9 months. Serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of treatment. Only 1.5% of the patients had serum triglyceride levels above 400 mg%. No laboratory abnormalities were a cause for discontinuation of treatment. During a 6-year follow up only 3.5% of patients received a second course of therapy with isotretinoin. CONCLUSIONS: Aside from its teratogenic effect, isotretinoin is a safe and excellent drug for acne therapy. It should be prescribed for any inflammatory acne and in our opinion there is no need for a routine laboratory follow-up in young, healthy patients aside from a pregnancy test in females. At present, isotretinoin should be considered as the drug of choice for moderate to severe acne. ( J Dermatol Treat (2001) 12: 9-12)
Angiogenesis genes, dietary oxidative balance and breast cancer risk and progression: The breast cancer health disparities study

Angiogenesis is essential for tumor development and progression. Genetic variation in angiogenesis‐related genes may influence breast carcinogenesis. We evaluated dietary factors associated with oxidative balance, DDIT4 (one SNP), FLT1 (35 SNPs), HIF1A (four SNPs), KDR (19 SNPs), MPO (one SNP), NOS2A (15 SNPs), TEK (40 SNPs) and VEGFA (eight SNPs) and breast cancer risk among Hispanic (2,111 cases and 2,597 controls) and non‐Hispanic white (1,481 cases and 1,586 controls) women in the Breast Cancer Health Disparities Study. Adaptive rank truncated product (ARTP) analysis was used to determine gene and pathway significance with breast cancer. TEK was associated with breast cancer overall (pARTP = 0.03) and with breast cancer survival (pARTP = 0.01). KDR was of borderline significance overall (pARTP = 0.07), although significantly associated with breast cancer in both low and intermediate Native American (NA) ancestry groups (pARTP = 0.02) and estrogen receptor (ER)+/progesterone receptor (PR)− tumor phenotype (pARTP = 0.008). Both VEGFA and NOS2A were associated with ER−/PR− tumor phenotype (pARTP = 0.01 and pARTP = 0.04, respectively). FLT1 was associated with breast cancer survival among those with low NA ancestry (pARTP = 0.009). With respect to diet, having a higher dietary oxidative balance score (DOBS) was significantly associated with lower breast cancer risk [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.64–0.84], with the strongest associations observed for women with the highest NA ancestry (OR 0.44, 95% CI 0.30–0.65). We observed few interactions between DOBS and angiogenesis‐related genes. Our data suggest that dietary factors and genetic variation in angiogenesis‐related genes contribute to breast cancer carcinogenesis.
Deconstructing the associations between executive functioning, problematic alcohol use and intimate partner aggression: A dyadic analysis

INTRODUCTION AND AIMS Problematic drinking and executive functioning deficits are two known risk factors for intimate partner aggression (IPA). However, executive functioning is a multifaceted construct, and it is not clear whether deficits in specific components of executive functioning are differentially associated with IPA perpetration generally and within the context of problematic alcohol use. To address this question, the present study investigated the effects of problematic drinking and components of executive functioning on physical IPA perpetration within a dyadic framework. DESIGN AND METHODS Participants were 582 heavy drinking couples (total n = 1164) with a recent history of psychological and/or physical IPA recruited from two metropolitan cities in the USA. Multilevel models were used to examine effects within an actor-partner interdependence framework. RESULTS The highest levels of physical IPA were observed among actors who reported everyday consequences of executive functioning deficits related to emotional dysregulation whose partners were problematic drinkers. However, the association between executive functioning deficits related to emotional dysregulation and IPA was stronger towards partners who were non-problematic drinkers relative to partners who were problematic drinkers. No such effect was found for executive functioning deficits related to behavioural regulation. DISCUSSION AND CONCLUSIONS Results provide insight into how problematic drinking and specific executive functioning deficits interact dyadically in relation to physical IPA perpetration. [Parrott DJ, Swartout KM, Eckhardt CI, Subramani OS. Deconstructing the associations between executive functioning, problematic alcohol use and intimate partner aggression: A dyadic analysis. Drug Alcohol Rev 2017;36:88-96].
CONVERGENCE RATES OF SUMS OF α-MIXING TRIANGULAR ARRAYS: WITH AN APPLICATION TO NONPARAMETRIC DRIFT FUNCTION ESTIMATION OF CONTINUOUS-TIME PROCESSES

The convergence rates of the sums of α-mixing (or strongly mixing) triangular arrays of heterogeneous random variables are derived. We pay particular attention to the case where central limit theorems may fail to hold, due to relatively strong time-series dependence and/or the nonexistence of higher-order moments. Several previous studies have presented various versions of laws of large numbers for sequences/triangular arrays, but their convergence rates were not fully investigated. This study is the first to investigate the convergence rates of the sums of α-mixing triangular arrays whose mixing coefficients are permitted to decay arbitrarily slowly. We consider two kinds of asymptotic assumptions: one is that the time distance between adjacent observations is fixed for any sample size n; and the other, called the infill assumption, is that it shrinks to zero as n tends to infinity. Our convergence theorems indicate that an explicit trade-off exists between the rate of convergence and the degree of dependence. While the results under the infill assumption can be seen as a direct extension of those under the fixed-distance assumption, they are new and particularly useful for deriving sharper convergence rates of discretization biases in estimating continuous-time processes from discretely sampled observations. We also discuss some examples to which our results and techniques are useful and applicable: a moving-average process with long lasting past shocks, a continuous-time diffusion process with weak mean reversion, and a near-unit-root process.
The Social Needs of the Discharged Mental Hospital Patient

URING recent years the importance of community care for patients suffering D from mental illness has been increasingly recognized and the Mental Health Acts (England and Wales, 1959, and Northern Ireland, 1961) provide for the expansion of community mental health services. It was thought that a study of the particular social problems of the discharged mental hospital patient and his family might provide information which would be of use in the development of these services.
Effect of Substrate Concentration on Carbon Isotope Fractionation during Acetoclastic Methanogenesis by Methanosarcina barkeri and M. acetivorans and in Rice Field Soil

ABSTRACT Methanosarcina is the only acetate-consuming genus of methanogenic archaea other than Methanosaeta and thus is important in methanogenic environments for the formation of the greenhouse gases methane and carbon dioxide. However, little is known about isotopic discrimination during acetoclastic CH4 production. Therefore, we studied two species of the Methanosarcinaceae family, Methanosarcina barkeri and Methanosarcina acetivorans, and a methanogenic rice field soil amended with acetate. The values of the isotope enrichment factor (ε) associated with consumption of total acetate (εac), consumption of acetate-methyl (εac-methyl) and production of CH4 (εCH4) were an εac of −30.5‰, an εac-methyl of −25.6‰, and an εCH4 of −27.4‰ for M. barkeri and an εac of −35.3‰, an εac-methyl of −24.8‰, and an εCH4 of −23.8‰ for M. acetivorans. Terminal restriction fragment length polymorphism of archaeal 16S rRNA genes indicated that acetoclastic methanogenic populations in rice field soil were dominated by Methanosarcina spp. Isotope fractionation determined during acetoclastic methanogenesis in rice field soil resulted in an εac of −18.7‰, an εac-methyl of −16.9‰, and an εCH4 of −20.8‰. However, in rice field soil as well as in the pure cultures, values of εac and εac-methyl decreased as acetate concentrations decreased, eventually approaching zero. Thus, isotope fractionation of acetate carbon was apparently affected by substrate concentration. The ε values determined in pure cultures were consistent with those in rice field soil if the concentration of acetate was taken into account.
Association of Endometriosis Risk and Genetic Polymorphisms Involving Sex Steroid Biosynthesis and Their Receptors: A Meta-Analysis

Endometriosis is a sex steroids-dependent disease. It has been postulated that certain genetic polymorphisms involved in sex steroids biosynthesis and metabolisms may be associated with increased risk of developing endometriosis. Despite a deluge of reports of positive associations of endometriosis with numerous polymorphisms involving sex steroids production and metabolism, the results are often conflicting. We performed a meta-analysis of 12 association studies on 5 genes (CYP17, CYP19, AR, PR and ER). We found that many reported positive findings were not supported by the data due to faulty analysis. There have been no functional data that support a putative relationship of these genetic polymorphisms with endometriosis. A handful of positive findings so far have not been independently replicated, and should be viewed as preliminary. In addition, these findings should be counterbalanced by legitimate concerns of multiple comparisons, small prior probability of association with a particular polymorphism, proper selection of controls, and lack of replication (at least until now). In future association studies, it may be productive to put more thought to study design, execution, and data analysis.
Dark‐adaptation and the regeneration of rhodopsin

Ever since Kohlrausch (1922) measured dark-adaptation by plotting the logarithm of the threshold against the time in the dark, it has been clear that the recovery of visual sensitivity occurs in two stages. For, in general, the curve plotted exhibits two quasi-independent branches which meet at a pretty sharp kink. As Kohlrausch demonstrated, the early and faster process is associated with day vision: the later process with night vision. An enormous amount of subsequent work has substantiated this interpretation, but we are on much less secure grounds if we conclude (as is often done) that the first branch is concerned with cones only, the second with rods only and that there is no rod-cone interaction. The 'cone branch' is obtainable from the rod-free fovea; it has the spectral sensitivity of daylight vision, monochromatic test flashes are usually seen as coloured, acuity is good, and a large Stiles-Crawford effect is found. This is strong evidence that cones are involved, but weak evidence that rods are not involved. To be sure, they are not involved at the central fovea, but the cone branch there is not quite the same shape as that found at the parafovea, where rods are anatomically present (Hecht, Haig & Wald, 1935; Sloan, 1950). The 'rod branch' is obtainable from all parts of the retina where rods are present and is absent from the only places (fovea and blind spot) where they are not. This branch exhibits the spectral sensitivity of twilight vision which (after correction for absorption by the ocular media) corresponds very closely to the absorption spectrum of rhodopsin (Crescitelli & Dartnall, 1953), a photosensitive pigment which can be seen contained in the living rods (Boll, 1876). Test flashes appear colourless whatever their wave-length, acuity is poor and the Stiles-Crawford effect is small or absent. This is strong proof that rods are involved, but evidence is not so clear whether cones contribute or not. If rhodopsin is the only pigment which absorbs quanta at threshold throughout the second branch, then after any
Performance degradation of an LC-tank VCO by impact of digital switching noise

In mixed-signal designs, digital switching noise is an important limitation for the analog and RF performance. This paper reports a thorough experimental and analytical study of the impact of digital switching noise on a 3.5 GHz LC-tank voltage controlled oscillator (VCO) in 0.18 /spl mu/m CMOS. Frequency modulation is recognized as the dominating mechanism behind the impact of digital switching noise in the investigated frequency range (DC to 15 MHz). The dominating coupling path, from the source of noise to the VCO, in this frequency range is via the non-ideal metal ground lines.
False CAM Alarms from Radon Fluctuations

The root cause of many false continuous air monitor (CAM) alarms is revealed for CAMs that use constant spectral shape assumptions in transuranic (TRU) alpha activity determination algorithms. This paper shows that when atmospheric radon levels continually decrease and bottom out at a minimum level, reduced false TRU count rates are not only expected but measured. Similarly, when the radon levels continually increase to a maximum level, elevated false TRU count rates were measured as predicted. The basis for expecting this dependence on changes in radon levels is discussed.
Suppression of MUC1 synthesis downregulates expression of the epidermal growth factor receptor

The transmembrane mucin, MUC1, is overexpressed on many human carcinoma cells, increasing their metastatic potential through decreased cell-cell and cell-matrix adhesion. These cellular changes are mediated both through the altered physical properties of the mucin itself and through the role of the MUC1 cytoplasmic domain as a signaling molecule. The epidermal growth factor receptor (EGFR) is also overexpressed in many cancers and both it and MUC1 constitute important therapeutic targets. In the present study, expression of MUC1 was downregulated by treatment of KB carcinoma cells with a MUC1 small interfering RNA resulting in an inhibition of cell proliferation and colony formation and an increase in cell-cell aggregation. Surprisingly, suppression of MUC1 also inhibited expression of EGFR at both the mRNA and protein levels whereas the reciprocal effect was not observed. These results demonstrate a role for MUC1 in the regulation of EGFR expression and suggest that MUC1 gene silencing may represent a novel therapeutic approach in the treatment of a variety of human cancers.
Creating a Learning Organization

A powerful new approach is now taking shape: the concept of the learning organization. This approach engages employees’ hearts and minds in continuous, harmonious, productive change designed to achieve results that they genuinely care about and that the organization’s stakeholders want. We are confident that the concept of the learning organization will have long-term value. It keeps emerging as a central theme in our work with clients, and we find it is crucial to our success in fostering innovation and positive change, both on behalf of our clients and in Arthur D. Little’s own knowledge creation processes worldwide.
Separation of malignant cells during autotransfusion

La retransfusion de sang autologue apres chirurgie pour cancer reduit les besoins en sang de donneur et les risques de transmission de virus HIV. Mais le sang traite par «Haemonetics Cell Saver», dispositif qui separe les hematies des cellules nucleees et les remet en suspension, contient encore des cellules malignes, provenant du site de chirurgie ou deja presentes dans le sang circulant
H3N2 canine influenza virus with the matrix gene from the pandemic A/H1N1 virus: infection dynamics in dogs and ferrets

SUMMARY After an outbreak of pandemic influenza A/H1N1 (pH1N1) virus, we had previously reported the emergence of a recombinant canine influenza virus (CIV) between the pH1N1 virus and the classic H3N2 CIV. Our ongoing routine surveillance isolated another reassortant H3N2 CIV carrying the matrix gene of the pH1N1 virus from 2012. The infection dynamics of this H3N2 CIV variant (CIV/H3N2mv) were investigated in dogs and ferrets via experimental infection and transmission. The CIV/H3N2mv-infected dogs and ferrets produced typical symptoms of respiratory disease, virus shedding, seroconversion, and direct-contact transmissions. Although indirect exposure was not presented for ferrets, CIV/H3N2mv presented higher viral replication in MDCK cells and more efficient transmission was observed in ferrets compared to classic CIV H3N2. This study demonstrates the effect of reassortment of the M gene of pH1N1 in CIV H3N2.