Miracle-dz/UniFAR-FTUs huggingface dataset:
Dentatorubral-pallidoluysian Atrophy: An Update

Background Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominantly inherited disorder characterized by myoclonus, epilepsy, ataxia, and dementia. Diagnosis is challenging due to the heterogeneous presentation and symptomatic overlap with other spinocerebellar ataxias. Symptoms vary according to age of onset, with a mean age at onset of 31 years. A CAG repeat expansion in the ATN1 gene results in neuronal intranuclear inclusions, variable neuronal loss, and astrocytosis in the globus pallidus, dentate and red nuclei. No disease-modifying or curative treatments are currently available Methods We performed an online literature search using PubMed for all articles published in an English Language format on the topics of DRPLA or ATN1 over the last 10 years. Where these articles cited other research as support for findings, or statements, these articles were also reviewed. Contemporary articles from related research fields (e.g., Huntington’s Disease) were also included to support statements. Results Forty-seven articles were identified, 10 were unobtainable and 10 provided no relevant information. The remaining 27 articles were then used for the review template: seven case reports, seven case series, six model system articles (one review article), four population clinical and genetic studies (one review article), two general review articles, and one human gene expression study. Other cited articles or research from related fields gave a further 42 articles, producing a total of 69 articles cited: 15 case series (including eight family studies), 14 model systems (one review article), 14 population clinical and genetic studies (two review articles), 10 case reports, eight clinical trials/guidelines, four genetic methodology articles, three general review articles, and one human gene expression study. Discussion DRPLA remains an intractable, progressive, neurodegenerative disorder without effective treatment. Early recognition of the disorder may improve patient understanding, and access to services and treatments. Large-scale studies are lacking, but are required to characterize the full allelic architecture of the disorder in all populations and the heterogeneous phenotypic spectrum, including neuroimaging findings, possible biomarkers, and responses to treatment.
Current treatment options for management of anal intraepithelial neoplasia

: Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus . Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus . High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO 2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects.
Longitudinal MRI data analysis in presence of measurement error but absence of replicates

ABSTRACT Longitudinal data analysis has found immense importance in biomedical fields to assess relationships between an outcome and its explanatory variables over time. However, this analysis is unreliable in presence of measurement errors in response data because the errors confound the effect of any signal caused by process changes. This confounding can be easily resolved by estimating and isolating the measurement errors using replicated measurements; i.e., multiple measurements in a small (stationary) time interval. However, in many medical applications, such as in magnetic resonance imaging (MRI), taking replicated measurements is not possible due to cost and/or risk considerations. This makes measurement error estimation and data analysis very challenging. In this article, we propose a novel method for the analysis of unreplicated longitudinal data under the presence of measurement errors. We formulate the problem using mixed-effect regression and develop a new EM-Variogram technique to estimate regression coefficients as well as variance components. The proposed approach decouples the confounded observed variance into the process and measurement system variances, and helps construct precise confidence intervals, leading to a more powerful statistical hypothesis test for the model parameters. We validate the proposed method using simulation and also apply it to a longitudinal MRI data for patients with neurodegenerative diseases. The results show improved statistical power in measuring their hippocampal volume loss, and a quicker degeneration detection. We also demonstrate the robustness of the proposed method with respect to missing values, a common issue in longitudinal data.
Local Isotropy Indicator for SAR Image Filtering: Application to Envisat/ASAR Images of the Doñana Wetland (November 2014)

This paper explores a geometrical and computationally simple operator, named Ds, for local isotropy assessment on SAR images. It is assumed that isotropic intensity distributions in natural areas, either textured or nontextured, correspond to a single cover class. Ds is used to measure isotropy in processing neighborhoods and decide if they can be considered as belonging to a unique cover class. The speckle statistical properties are used to determine suitable Ds thresholds for discriminating heterogeneous targets from isotropic cover types at different window sizes. An assessment of Ds as an edge detector showed sensitivities similar to those of the ratio edge operator for straight, sharp boundaries, centered in the processing window, but significantly better sensitivity for detecting heterogeneities during the window expansion in multiresolution filtering. Furthermore, Ds presents the advantage versus the ratio edge coefficient of being rotationally invariant, and its computation indicates the direction of the main intensity gradient in the processing window. The Ds operator is used in a multiresolution fashion for filtering ASAR scenes of the Doñana wetland. The intensities in isotropic areas are averaged in order to flatten fluctuations within cover types and facilitate a subsequent land cover classification. The results show high degree of smoothing within textured cover classes, plus effective spatial adaptation to gradients and irregular boundaries, substantiating the usefulness of this operator for filtering SAR data of natural areas with the purpose of classification.
The SJL/J mouse is not a model for PBC

Interferon combined with ribavirin is the most effective treatment of chronic hepatitis C. Ribavirin is associated with reversible hemolytic anemia. The underlying mechanism is unknown; oxidative damage of the erythrocyte membrane has been implied.1 As a nucleoside analogue, it is also linked to mitochondrial toxicity.2 The mean drop of hemoglobin in patients treated with combination interferon alfa-2b plus ribavirin is 2 to 3 g/dL, although a decrease of more than 4 g/dL occurs in about 10% to 20% of patients.3-5 Anemia may be poorly tolerated in patients because of the rapidity of the decrease of hemoglobin. The use of recombinant human erythropoietin alfa (rHuEPO) has been evaluated in the treatment of ribavirin/interferon-induced anemia in patients with hepatitis C.6 We are presenting a series of 13 patients with hepatitis C, who developed anemia on interferon alfa-2b/ribavirin treatment and who were treated with rHuEPO. The median age of the patients was 45 years (range 25-70). The sex ratio (male/female) was 5/8. The source of hepatitis infection was transfusion (4 cases), intravenous drug use (5 cases), health care worker (2 cases), and other or unknown in 2 cases. The estimated median duration of infection was 20 years (range 13-28). Nine patients were infected with genotype 1, 2 patients with genotype 3, and 2 with genotype 4. Three patients received previous treatment (1 was a nonresponder and 2 had relapse). One patient was infected with human immunodeficiency virus (HIV). One patient had thalassemia minor. Median baseline serum hepatitis C virus RNA level was 3 106 equivalent virion/mL (range 0.2-46.7) (bDNA Quantiplex 3.0). Median baseline METAVIR activity score was 2 (1-3) and fibrosis stage was 2 (1-4). Cirrhosis was present in 2 patients. Interferon alfa-2b was given at 6 million units 3 times a week to 9 patients and at 3 million units 3 times a week to 3 patients. PEG–interferon alfa-2b 80 g/wk was given to 1 patient, along with ribavirin 1 g or 1.2 g/d (12 and 1 patient, respectively) for 6 to 12 months. When anemia developed, rHuEPO was given at a dose of 4,000 units 2 to 3 times weekly to 11 patients, 8,000 units 3 times weekly to 1 patient, and 10,000 units 3 times weekly to 2 patients. Baseline median hemoglobin was 13.3 g/dL (range 12.2-15.8) and hemoglobin nadir was 10.2 g/dL (range 8.4-11.2). On rHuEPO the hemoglobin increased to a median of 11.5 g/dL (range 9.6-12.8). None of the patients on rHuEPO stopped treatment because of anemia. The ribavirin dose had been decreased before rHuEPO was given to 800 mg in 3 patients, to 600 mg in 1 patient, and to 200 mg in 1 patient who had cirrhosis at liver biopsy and was HIV positive. Ten patients responded to interferon/ribavirin treatment; 3 patients did not. Of the 10 initial responders, 4 had sustained response, 5 are still under treatment or follow-up, and 1 patient relapsed. Three cases are illustrated in Fig. 1. In conclusion, in our cohort of patients with chronic hepatitis C treated with interferon/ribavirin combination
Human Capital, Fertility, and Economic Growth

Our analysis of growth assumes endogenous fertility and a rising rate of return on human capital as the stock of human capital increases. When human capital is abundant, rates of return on human capital investments are high relative to rates of return on children, whereas when human capital is scarce, rates of return on human capital are low relative to those on children. As a result, societies with limited human capital choose large families and invest little in each member; those with abundant human capital do the opposite. This leads to two stable steady states. One has large families and little human capital; the other has small families and perhaps growing human and physical capital.
An Empirical Examination of Information Barriers to Trade in Insurance

This paper tests restrictions implied by the canonical theory of insurance under asymmetric information using ideal data that contains the self-perceived and actual mortality risk of individuals, as well as the price and quantity of their life insurance. We report several findings which are hard to reconcile with the canonical theory. First, we find a striking independence of self-perceived risk and the price of insurance. Second, we find strong evidence of the opposite type of non-linear pricing than predicted by theory: the theory predicts that prices rise with quantity, but we find that they fall. Third, we find that risk is negatively correlated with the quantity of insurance purchased although the theory predicts a positive correlation. Fourth, we find that a substantial fraction of individuals hold multiple insurance contracts, which casts doubt on the prediction that unit prices rise with quantity because multiple small contracts dominate a large one in such a case. Lastly, we test the accuracy of the self-perceived risk of the insured through estimating the induced profits they imply. We conclude by discussing the robustness of these results and the questions they raise for future theoretical models.
Immunohistochemical localization of β-amylase in resting barley seeds

The cellular localization of β-amylase (EC 3.2.1.2) in resting barley seeds was investigated by immunohistochemistry. The monospecificity of the antibodies used was shown by immunoelectrophoresis and western blotting. An adaptation of the immunofluorescence technique allowed the localization of β-amylase. free of autofluorescence, in the different parts of the seed. In endosperm, there was β-amylase protein in aleurone layers, only in the starchy endosperm, where the distribution of the enzyme was not uniform. The β-amylase of starchy endosperm. which can be in a free or a hound form, was mainly localized around starch granules of different sizes. In the embryo. β-amylase was present only in the part of the scutellum in front of the first leaf. By immunoquantitation after separation of the seed parts, its was shown that the ratio between the amounts of enzyme in embryo and endosperm was less than 1/3000.
A Test of Dual Labor Market Theory

Despite substantial differences in their views of the appropriate policy response to the existence of poverty, neither the proponents of dual market theory nor its critics have proposed potentially conclusive tests of the dual market hypothesis.This paper presents a test of the two central propositions of dual market theory -- 1) the existence of two distinct labor markets with different wage setting mechanisms and 2) the existence of barriers to mobility between the labor markets. We find considerable support for both hypothesis. Estimation of a switching model of wage determination with unknown regimes yields two distinct wage equations. The one which most workers are associated with closely resembles the standard human capital regression with significant returns to education and experience. The other equation is flat with no returns to human capital. These two equations resemble the predictions of dual market theory for the "primary" and "secondary" markets respectively. Further, we present evidence that(at least) some non-white workers are involuntarily confined to the secondary market. This crowding of minority workers into the low wage labor market accounts for a substantial portion of white/non-white wage differences. We interpret these results as providing empirical support for the dual market hypothesis and for recent theoretical work on efficiency wagemodels. In addition, combining the efficiency wage argument with the observation that much of the white/non-white wage difference is explained by the exclusion of non-whites from the primary sector suggests an explanation for the persistance of wage differences.
The R-word index for Switzerland

In a pioneering attempt, we present the R(ecession)-word index for Switzerland. We evaluate its predictive ability of GDP growth using real-time vintages of GDP data, closely simulating flow of information in the past. We find that inclusion of the R-word index led to a statistically significant improvement in forecast accuracy over the benchmark autoregressive (AR) model. Largest improvements in forecast accuracy were observed in the period around the Great Recession.
Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain

Simple Summary Accumulating evidence indicates that hypoxia-inducible factor-1 (HIF-1) plays a pivotal role in tumor biology, particularly in hypoxic environments. Over the past few decades, a number of HIF-1 inhibitors have been identified as potential therapeutic agents for various cancers. However, none of these inhibitors have been successfully translated into clinically available cancer treatments. This review describes the HIF-1 pathway and its roles in tumor proliferation, angiogenesis, and metastasis. In addition, the implications of HIF-1 in the development of drug resistance and cancer-related pain are explored. Finally, the current status of HIF-1 inhibitors in clinical trials and their future perspectives are highlighted, along with their modes of action. This review provides new insights into anticancer drug development targeting HIF-1. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain. Abstract Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts have been made to comprehensively understand the role of HIF-1 in tumor progression. Based on the pivotal roles of HIF-1 in tumor biology, many HIF-1 inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity have been identified as potential therapeutic agents for various cancers, yet none of these inhibitors have yet been successfully translated into clinically available cancer treatments. In this review, we briefly introduce the regulation of the HIF-1 pathway and summarize its roles in tumor cell proliferation, angiogenesis, and metastasis. In addition, we explore the implications of HIF-1 in the development of drug resistance and cancer-related pain: the most commonly encountered obstacles during conventional anticancer therapies. Finally, the current status of HIF-1 inhibitors in clinical trials and their perspectives are highlighted, along with their modes of action. This review provides new insights into novel anticancer drug development targeting HIF-1. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain.
Diabetes in midlife and cognitive change over 20 years: the Atherosclerosis Risk in Communities Neurocognitive Study

Background— Type 2 diabetes mellitus is associated with dementia risk, however evidence is limited for possible associations of diabetes and pre-diabetes with cognitive decline. Objective— To determine if diabetes in mid-life is associated with 20-year cognitive decline, and to characterize long-term cognitive decline across clinical categories of hemoglobin A1c (HbA1c). Design— Prospective cohort. Setting— The community-based Atherosclerosis Risk in Communities (ARIC) Study. Participants— 13351 black and adults aged 48-67 years at baseline (1990-1992). Measurements— Diabetes was defined by self-report of physician diagnosis or medication use or HbA1c≥6.5%. Undiagnosed diabetes, pre-diabetes, and glucose control in persons with diagnosed diabetes were defined using clinical categories of HbA1c. Delayed Word Recall, Digit Symbol Substitution, and Word Fluency tests were used to assess cognitive performance, and were summarized using a global Z-score. Results— Diabetes in midlife was associated with significantly greater cognitive decline over 20 years (adjusted global Z-score difference=-0.15, 95% CI:-0.22,-0.08), representing a 19% greater decline than those without diabetes. Cognitive decline was significantly greater among persons with pre-diabetes (HbA1c 5.7-6.4%) than those without diabetes and HbA1c<5.7%. Participants with poorly controlled diabetes (HbA1c≥7.0%) had a larger decline compared to persons whose diabetes was controlled (adjusted global Z-score difference=-0.16,p-value=0.071). Longer duration of diabetes was also associated with greater late-life cognitive decline (p-value-for-trend=<0.001). No significant differences in the rates of declines were seen in whites compared to blacks (p-value-for-interaction=0.4357). Limitations— Single measurement of HbA1c at baseline, only one test to per cognitive domain, potential geographic confounding of race comparisons. Conclusions— These findings suggest that diabetes prevention and glucose control in midlife may protect against late-life cognitive decline.
Screening for osteoporosis.

PURPOSE To review evidence that screening for osteoporosis by measuring bone mass in postmenopausal women would reduce fracture incidence. DATA IDENTIFICATION An English-language literature search using MEDLINE (1966 to 1989), bibliographic reviews of book chapters and review articles, technology assessments of bone mass measurement, and other publications. STUDY SELECTION We summarize prospective studies of fracture risk prediction done with widely used bone mass measurement techniques, and we document noncontroversial or peripheral points with recent papers and reviews. DATA EXTRACTION Without osteoporosis screening trials, no quantitative analysis is possible. Instead, we assess the ability of screening tests to measure bone mass and define fracture risk categories, the ability of risk categories to determine treatment, and the ability of treatment to reduce fracture incidence. RESULTS OF DATA SYNTHESIS Bone mass measurement meets many of the criteria for a screening test, and indirect evidence suggests that a screening program might reduce osteoporosis-related fracture incidence. No trial has shown this directly; however, and questions remain about overall benefits and costs of mass screening. CONCLUSIONS Although there are clinical indications for bone mass measurement, unselective screening for osteoporosis cannot be recommended until a specific program is formulated and justified.
Prevalence of Autism Spectrum Disorders (ASD) and its association with medical issues and behaviour problems among Children with Intellectual Disability (ID)

Background: The presence or absence of Intellectual Disability(ID) has been recognized as one of the strongest determinant of outcomes for individuals with Autism Spectrum Disorder(ASD). Behavioural problems which are commonly reported in autism may be related to core features of autism, comorbid diagnoses or symptoms . There is paucity of Indian studies on prevalence of ASD among children diagnosed with ID and also the prevalence of behaviour problems in this population. This study was conducted with the objectives to assess the prevalence of ASD in the intellectually disabled, as well as the associated comorbidity patterns. Methodology: It was a cross sectional study including 122 children with mild/moderate Intellectual Disability between 6 to 18 years. Indian Scale for Assessment of Autism(ISAA), Behaviour Problems Inventory(BPI) was administered and questions were asked to know medical symptoms. Results: Prevalence of co-morbid ASD in children with ID was with 16.39%. Children with ASD had higher behavioural problems (p=0.001), higher medical complaints like GI symptoms (constipation p=0.001, bloating p=0.03, abdominal pain p=0.03) and seizure (p=0.002). Behaviour problems were higher in children with more severe autism scores. Conclusion: There is a notable prevalence of ASD in children with ID. These children tend to have higher behavioural problems and co-morbid medical issues which needs clinical attention for better overall management of these children.