Miracle-dz/UniFAR-FTUs huggingface dataset:
Allopurinol Hypersensitivity Syndrome: A Review

OBJECTIVE: To review the pathophysiology, pathology, and clinical findings of allopurinol hypersensitivity syndrome (AHS), an infrequent but life-threatening adverse effect of allopurinol therapy. DATA SOURCES: A MEDLINE search (key terms hepatitis, interstitial nephritis, severe hypersensitivity, severe toxicity, vasculitis, toxic epidermal necrolysis, Lyell's syndrome, erythema multiforme, and Stevens-Johnson syndrome) was used to identify cases reported in the literature through the end of 1990. STUDY SELECTION: All cases evaluated met Singer and Wallace's diagnostic criteria for AHS. DATA EXTRACTION: We extracted data from 101 cases of AHS reported in the literature. The following information, when available, was analyzed: (1) patient data (age, gender, medical history), (2) treatment data (daily dosage of allopurinol, duration of treatment, indications, concomitant medications, and (3) adverse-event data. DATA SYNTHESIS: Patients were mostly middle-aged men with hypertension and/or renal failure receiving excessive doses of allopurinol primarily for asymptomatic hyperuricemia. Cutaneous rash and fever were the most common clinical findings. CONCLUSIONS: Although the pathophysiologic pathway leading to the development of AHS is unknown, it probably involves an immunologic mechanism following allopurinol accumulation in patients with poor renal function. Our findings suggest that the accepted diagnostic criteria for AHS may be too broad, and we recommend the application of more restrictive criteria. There is no effective treatment for AHS. The use of allopurinol only for accepted indications and in dosages adjusted for a patient's renal function may be the only means of minimizing the incidence of AHS.
Crisis and extremism. How does an extreme far right emerge in a modern democracy? Evidence from Greece’s Golden Dawn

ABSTRACT We trace the rise of Golden Dawn, one of the most extreme and violent European far-right parties, from the fringe to a prominent position in Greek politics. We use regression analysis to show that its rise is associated with changes in voting behavior caused by the deep socioeconomic crisis the country went through after 2008. We show that the demand factors affecting the GD vote were triggered by structural changes in the supply side and the implosion of the two-party system that followed the signing of the bail-out agreement (Memorandum) with the country’s creditors. Our results have implications about the political manifestation of socioeconomic grievances and their effect on the far-right vote: whereas socioeconomic grievances usually contribute towards a latent dissatisfaction by the electorate, this might need a sudden supply-side trigger in order to manifest itself, giving little warning signs in advance.
Prognostic significance of spontaneous antibody responses against tumor‐associated antigens in malignant melanoma patients

Distribution, patterns and prognostic impact of spontaneous antibody responses against different tumor‐associated antigens (TAAs) in malignant melanoma patients are unknown so far and were investigated in this study for the first time in a large cohort at different stages of the disease, identifying new prognostic biomarkers for malignant melanoma. Serum samples from 365 melanoma patients (97 Stage I melanoma patients, 87 Stage II, 92 Stage III and 89 Stage IV) and 100 age and gender matched healthy control donors were analyzed. Samples were drawn at the time of diagnosis (Stages I–III) or at time of diagnosis of distant metastasis (Stage IV). Applying a novel multiplex assay, humoral immune responses against 29 TAAs were determined and the association between response and patient survival was investigated. Antibody responses were mainly found in melanoma patients and all tested antigens elicited immune responses in all disease stages. Antibody responses against single antigens were either associated with poor prognosis and/or shorter progression‐free survival (PFS) or had no influence. While in Stages I–III significant associations were observed between an antibody response and overall survival or PFS, among Stage IV patients, no significant association was found. Multivariate analyses identified specific humoral immune responses as prognostic factors independently of age, chemotherapy and immunotherapy. Antibody responses against specific TAA in Stage I‐III melanoma patients correlate with poor prognosis and/or shorter PFS. These results may help to design clinical studies in order to evaluate the potential of these responses as prognostic serological biomarkers.
The Morality of National Defense: An Aristotelian-Thomist Account

In current just war theory debates, some scholars claim that a moral right to defend a nation cannot be demonstrated. Others claim that any case for the morality of even defensive war must reflect standards of interpersonal morality. This dissertation goes back to the natural law tradition behind just war theory to offer a moral argument in favor of national defense that is not based on an individualist account, but also rejects absolute accounts of national sovereignty, with its attendant problems. National defense is usually but not always just. I defend arguing from “a tradition” in MacIntyre’s sense, and distinguish Aristotelian-Thomist natural law, my tradition, from post-Grotius and “new” natural law. ” I defend the tradition against Hume’s attack on moving from “what is” to “what ought to be. ” I stress the natural law revival in jurisprudence since the weakness of positive law to deal with World War II intra-state crimes became clear at Nuremberg. As the tradition differs sharply from much current moral reasoning, I elucidate five areas of difference: a social approach vs. individualism, an architectural approach vs. an exploration of intuitions, primarily subjective vs. primarily objective evaluation, belief in human nature vs. a denial of it, and a stress on justice vs. subjective human rights. I ground individual defense in a morality based on the objective value of human (and other forms of) existence and the telos of flourishing individually and as groups. I argue for a proportionate use of force to defend property. I base the justice of defending a state on its necessity for human flourishing, its natural duty to defend its citizens, and the necessity of defense for ongoing existence. I next argue against opposing positions, in terms of their own traditions, primarily Jeff McMahan and David Rodin. I critique both for rejecting the morality of defense against innocent threats, for bad derivations of individual rights, and for objective approaches to morality. I further critique McMahan for his claim liability to be killed can rest on a responsibility less than culpability. I then critique Rodin on a variety of internal logical grounds.
Diversity and the maintenance of sex by parasites

The Red Queen hypothesis (RQH) predicts that parasite‐mediated selection will maintain sexual individuals in the face of competition from asexual lineages. The prediction is that sexual individuals will be difficult targets for coevolving parasites if they give rise to more genetically diverse offspring than asexual lineages. However, increasing host genetic diversity is known to suppress parasite spread, which could provide a short‐term advantage to clonal lineages and lead to the extinction of sex. We test these ideas using a stochastic individual‐based model. We find that if parasites are readily transmissible, then sex is most likely to be maintained when host diversity is high, in agreement with the RQH. If transmission rates are lower, however, we find that sexual populations are most likely to persist for intermediate levels of diversity. Our findings thus highlight the importance of genetic diversity and its impact on epidemiological dynamics for the maintenance of sex by parasites.
Expression of ADAM28 and IGFBP-3 Genes in Patients with Colorectal Cancer — A Preliminary Report

Adamalisynes (ADAMs) play an important role in inter-membrane interactions, cell adhesion and fusion processes and protein shedding from the cell surface. Many reports indicate that members of the ADAMs family are overexpressed in human cancer. The aim of the present study was to evaluate ADAM28 and Insulin Like Growth Factor Binding Protein-3 (IGFBP-3)) gene expression in colorectal carcinoma tissues with regard to the overweight or obese status of the patients using an oligonucleotide microarray technique. Fresh tissue specimens were obtained from colorectal cancer patients during surgical treatment. Eighteen specimens from tumour and 18 normal tissue specimens from colorectal cancer patients at clinical stages III and IV were analysed. The examined patients were divided into two groups; those with BMI≥25 and those with normal BMI. The control group consisted of 18 specimens of non-neoplastic colon tissues, which were divided between overweight/obese and normal body weight patients. The gene transcriptional activity from the specimens was analysed using an oligonucleotide microarray technique. Microarrays and rinsing and marking solutions were prepared according to the procedure in the Gene Expression Analysis Technical Manual. The following conclusions were made: i) change of ADAM28 and IGFBP-3 genes expression are present in the normal tissue in overweight/obese patients with colorectal cancer only; ii) the observed molecular variability of ADAM28 and IGFBP-3 expression may be an initial process of cancer proliferation; iii) the histopathologically normal surgical margin in this group of patients was not equal to the molecular margin.
The effects of alpha‐helix on the stability of Asn residues: Deamidation rates in peptides of varying helicity

Asn deamidation was monitored in Ala‐based octadecapeptides of varying α‐helicity. Gly was substituted for Ala residues at positions 6 and 16 to create a peptide with less helicity. Ala → Gly substitutions were made at three or more residues from the Asn to negate known primary sequence effects on deamidation rates. The extent of helicity and rate of Asn deamidation for alkaline aqueous solutions of each peptide was measured as a function of temperature by circular dichroism and reversed‐phase high‐performance liquid chromatography, respectively. The rate of deamidation in the peptides was inversely proportional to the extent of α‐helicity. The results support the conclusion that Asn deamidation only occurs in the nonhelical population of conformers.
Severe Combined Immunodeficiences: New and Old Scenarios

Severe combined immunodeficiencies (SCIDs) represent a group of distinct congenital disorders affecting either cell-mediated or humoral immunity, which lead invariably to severe and life-threatening infections. The different forms of SCID are currently classified according to the presence or absence of T, B, and NK cells. This greatly helps define the site of the blockage during the differentiation process. Even though SCID patients share common clinical features, such as opportunistic infections and failure to thrive, irrespective of the underlying pathogenetic mechanism, the discovery of new causative gene alterations led to identify novel complex clinical phenotypes, sometimes associated to extrahematopoietic manifestations. In a few cases, the presenting signs may be peculiar to that specific form and physicians should be alerted in recognizing such complex phenotypes, in order to avoid delay in the diagnostic procedures. The aim of this review is to alert care-givers to take into account also the less frequent clinical features and novel pathogenic mechanisms to direct the functional and molecular studies toward a certain genetic alteration.
Cost burden of type 2 diabetes in Germany: results from the population-based KORA studies

Objective To examine the impact of type 2 diabetes on direct and indirect costs and to describe the effect of relevant diabetes-related factors, such as type of treatment or glycaemic control on direct costs. Design Bottom-up excess cost analysis from a societal perspective based on population-based survey data. Participants 9160 observations from 6803 individuals aged 31–96 years (9.6% with type 2 diabetes) from the population-based KORA (Cooperative Health Research in the Region of Augsburg) studies in Southern Germany. Outcome measures Healthcare usage, productivity losses, and resulting direct and indirect costs. Methods Information on diabetes status, biomedical/sociodemographic variables, medical history and on healthcare usage and productivity losses was assessed in standardised interviews and examinations. Healthcare usage and productivity losses were costed with reference to unit prices and excess costs of type 2 diabetes were calculated using generalised linear models. Results Individuals with type 2 diabetes had 1.81 (95% CI 1.56 to 2.11) times higher direct (€3352 vs €1849) and 2.07 (1.51 to 2.84) times higher indirect (€4103 vs €1981) annual costs than those without diabetes. Cardiovascular complications, a long diabetes duration and treatment with insulin were significantly associated with increased direct costs; however, glycaemic control was only weakly insignificantly associated with costs. Conclusions This study illustrates the substantial direct and indirect societal cost burden of type 2 diabetes in Germany. Strong effort is needed to optimise care to avoid progression of the disease and costly complications.
6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial.

CONTEXT Survival benefit in the management of high-grade clinically localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of androgen suppression therapy (AST), but long-term AST is associated with many adverse events. OBJECTIVE To assess the survival benefit of 3-dimensional conformal radiation therapy (3D-CRT) alone or in combination with 6 months of AST in patients with clinically localized prostate cancer. DESIGN, SETTING, AND PATIENTS A prospective randomized controlled trial of 206 patients with clinically localized prostate cancer who were randomized to receive 70 Gy 3D-CRT alone (n = 104) or in combination with 6 months of AST (n = 102) from December 1, 1995, to April 15, 2001. Eligible patients included those with a prostate-specific antigen (PSA) of at least 10 ng/mL, a Gleason score of at least 7, or radiographic evidence of extraprostatic disease. MAIN OUTCOME MEASURES Time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits) and overall survival. RESULTS After a median follow-up of 4.52 years, patients randomized to receive 3D-CRT plus AST had a significantly higher survival (P =.04), lower prostate cancer-specific mortality (P =.02), and higher survival free of salvage AST (P =.002). Kaplan-Meier estimates of 5-year survival rates were 88% (95% confidence interval [CI], 80%-95%) in the 3D-CRT plus AST group vs 78% (95% CI, 68%-88%) in the 3D-CRT group. Rates of survival free of salvage AST at 5 years were 82% (95% CI, 73%-90%) in the 3D-CRT plus AST group vs 57% (95% CI, 46%-69%) in the 3D-CRT group. CONCLUSION The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinically localized prostate cancer.
Clinical characteristics and genotype analysis of patients with cystic fibrosis and nasal polyposis requiring surgery.

OBJECTIVE To analyze the clinical characteristics and genotypes of patients with cystic fibrosis (CF) and nasal polyposis who require surgery. DESIGN Cross-sectional analysis of a large patient database. SETTING Data obtained from the National CF Patient Registry of the Cystic Fibrosis Foundation, Bethesda, Md. PATIENTS Clinical and genotype data on 20198 patients with CF who were registered in 1992 and 1993 were analyzed. The study group (n = 815) consisted of patients with CF who had undergone surgical procedures for the treatment of nasal polyposis. The comparison group (n = 19383) comprised the remainder of the patients in the database. RESULTS Statistical analysis revealed that patients with CF and nasal polyposis who required surgery had better pulmonary function (higher percent-predicted forced expiratory volume in 1 second and forced vital capacity), better nutritional status, a higher rate of Pseudomonas aeruginosa colonization, more office visits, more hospitalizations, and a higher rate of acute exacerbations per year (P < .001 for each) than did the comparison group. Among the patients who had mutation analysis performed, patients with nasal polyposis who required surgery were significantly associated with 2 specific genotypes: the delta-F508/delta-F508 (57.5% vs 49.9%, P = .01) and the delta-F508/G551D (12% vs 8%, P = .05) genotypes. CONCLUSIONS Patients with CF and nasal polyposis who require surgery may constitute a clinical subgroup within the spectrum of the disease. These patients appear to have slightly better pulmonary function and nutritional status; yet, they seem to have a higher degree of health care utilization. The higher rate of P aeruginosa respiratory infection in this patient group suggests an association with the presence of nasal polyposis. Genotype analysis showed a higher prevalence of the delta-F508/delta-F508 and the delta-F508/G551D genotypes in this patient group.
Spreading word: author frequency of app user reviews

App stores allow developers to publish new updates directly to users. Users evaluate and leave public reviews of their opinions and experiences for others to see. App ratings and reviews are a purchase determinant for users, and are free user-based usability tests. Existing literature offers approaches to extract information from or to summarise app reviews, but what can we say about the authors themselves? We analysed about 8.7 million iOS app reviews written by over 5.5 million unique authors. We found that 71.5% of authors only wrote one review. Only 13,224 instances of authors re-reviewing were observed, by 12,667 authors for 3,345 apps.
Functional assessment of chronic obstructive pulmonary disease

Purpose: To describe available methods for assessing functional capacity in persons with chronic obstructive pulmonary disease (COPD). Data sources: An extensive literature review is used to provide pertinent information. Conclusions: COPD disease affects millions of Americans and is physically and psychologically distressing. The hallmark of chronic obstructive pulmonary disease is irreversible airflow limitation and dyspnea. Dyspnea is a major contributor to decreased exercise capacity and functional status in this population. Understanding the methods to complete a functional assessment is important for all practitioners caring for this population. Implications for practice: This paper provides an overview of current methods used to assess functional status, including pulmonary function testing, exercise testing, and anthropomorphic and self‐report measurements. In addition, there is discussion of the indications and contraindications for exercise testing in chronic obstructive pulmonary disease and the clinical significance of performing a global composite of functional ability. Disclosure The author reports no competing interests. To obtain CE credit for this activity, go to and click on the CE Center. Locate the listing for this article and complete the post‐test. Follow the instructions to print your CE certificate.
The Immunohistochemical Profile of Malignant Mesotheliomas of the Tunica Vaginalis: A Study of 20 Cases

Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. The immunohistochemical profile of the tunica vaginalis and associated neoplasms is often extrapolated from thoracic studies. Testicular series are uncommon, usually derived from previous case studies and literature reviews. The immunohistochemical findings in 20 cases originally diagnosed as malignant mesotheliomas are presented. Archival testicular malignant mesothelioma specimens from 1959 to 2004 were collected from hospitals throughout the United Kingdom and from the authors' own archives. Hematoxylin and eosin-stained sections were reviewed, and selected sections from each case were then examined using an immunohistochemical panel of eight antibodies: calretinin (Zymed, 1:200), epithelial membrane antigen (EMA) (DAKO, 1:50), thrombomodulin (DAKO 1:5), CK7 (DAKO, 1:100), CK5-CK6 (DAKO, 1:10), BerEp4 (DAKO, 1:25), carcinoembryonic antigen (CEA) (DAKO, 1:10), and CK20 (DAKO, 1:100). The EnVision technique was used for all antibodies. Sections were reviewed independently by three pathologists. Electron microscopy was performed on selected cases. In all cases, the morphologic light microscopy criteria for a diagnosis of malignant mesothelioma were present. However, two tumors were later excluded from the study because of diffuse strong positive immunostaining with CK20 and BerEp4 and an ultrastructural appearance of adenocarcinoma. Of the remaining cases, 15 of 18 (83%) were purely epithelioid in type, showing a mixture of papillary, tubular, and solid patterns, and 3 of 18 (17%) showed a mixed sarcomatoid/epithelioid pattern. All cases were positive for calretinin and EMA (100%), 16 of 18 (89%) were positive for thrombomodulin, and 15 of 18 (83%) were positive for CK7. CK5-CK6 positivity was present in 13 of 18 (72%) but varied in strength and distribution; 2 of 18 (11%) were positive for BerEp4. All the cases were negative for CK20 and CEA. Four of the 18 cases were examined by electron microscopy, which revealed long thin microvilli supporting a diagnosis of malignant mesothelioma. This study has shown that the immunocytochemical profile of testicular malignant mesotheliomas is similar to those arising in the pleura, with diffuse positivity for calretinin, EMA, thrombomodulin, and CK7, and negative for CK20 and CEA. Focal weak positivity may be encountered with BerEp4. However, histopathologists should be aware of the variability in CK5-6 staining in testicular specimens when compared with pleural mesotheliomas.