Miracle-dz/UniFAR-FTUs huggingface dataset:
EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA‐DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new ‘gold standard’ for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.
Prognostic significance of activated Akt expression in melanoma: a clinicopathologic study of 292 cases.

PURPOSE Akt is a serine/threonine kinase that leads to stimulation of cell cycle progression, cell proliferation, and inhibition of apoptosis. To investigate the role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt (p-Akt; Ser-473) in melanocytic lesions at different stages and analyzed the correlations between the p-Akt expression level and clinicopathologic factors and patient survival. PATIENTS AND METHODS We evaluated the p-Akt expression in 12 cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary melanomas, and 52 cases of melanoma metastases using tissue microarray and immunohistochemistry. RESULTS Strong p-Akt expression was observed in 17%, 43%, 49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for p-Akt staining pattern were observed between normal nevi and primary melanomas (P < .05), and between primary melanomas and melanoma metastases (P < .001). Furthermore, our Kaplan-Meier survival curves showed that strong p-Akt expression is inversely correlated with both overall and disease-specific 5-year survival of patients with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox regression analysis revealed that p-Akt is an independent prognostic factor in low-risk melanomas (thickness < or = 1.5 mm; relative risk, 6.44; 95% CI, 1.28 to 32.55; P = .018). CONCLUSION The expression of p-Akt increases dramatically with melanoma invasion and progression and is inversely correlated with patient survival. In addition, p-Akt may serve as an independent prognostic marker and help to identify those patients with low-risk melanomas who are at increased risk of death.
Ultrastructure of the Harmful Unarmored Dinoflagellate Cochlodinium polykrikoides (Dinophyceae) with Reference to the Apical Groove and Flagellar Apparatus

ABSTRACT. The external and internal ultrastructure of the harmful unarmored dinoflagellate Cochlodinium polykrikoides Margalef has been examined with special reference to the apical groove and three‐dimensional structure of the flagellar apparatus. The apical groove is U‐shaped and connected to the anterior sulcal extension on the dorsal side of the epicone. The eyespot is located dorsally and composed of two layers of globules situated within the chloroplast. A narrow invagination of the plasma membrane is associated with the eyespot. The nuclear envelope has normal nuclear pores similar to other eukaryotes but different from the Gymnodinium group with diagnostic nuclear chambers. The longitudinal and transverse basal bodies are separated by approximately 0.5–1.0 μm and interconnected directly by a striated basal body connective and indirectly by microtubular and fibrous structures. Characteristic features of the flagellar apparatus are as follows: (1) a nuclear extension projects to the R1 (longitudinal microtubular root) and is connected to the root by thin fibrous material; (2) fibrillar structures are associated with the longitudinal and transverse flagellar canal; and (3) a striated ventral connective extends toward the posterior end of the cell along the longitudinal flagellar canal. We conclude, based on both morphological and molecular evidence, that Cochlodinium is only distantly related to Gymnodinium.
Enoxaparin Prevents Progression of Stages I and II Osteonecrosis of the Hip

In a prospective pilot study, we hypothesized that enoxaparin (60 mg/day for 12 weeks) would prevent progression of Stages I and II osteonecrosis of the hip associated with thrombophilia or hypofibrinolysis or both over ≥ 108 weeks of followup versus untreated historic controls, with different treatment responses in primary versus corticosteroid-associated secondary osteonecrosis. Patients with one or more thrombophilic-hypofibrinolytic disorder and Ficat Stages I or II osteonecrosis of at least one hip were included. A blinded committee interpreted anteroposterior and frog-leg lateral radiographs at entry in the study and every 36 weeks to ≥ 108 weeks. Maintenance of the disease at Stages I and II versus progression of the osteonecrosis to Stages III and IV requiring total hip replacement was the major end point. Sixteen patients had primary osteonecrosis (25 hips; 13 Stage I, 12 Stage II), and 12 had secondary osteonecrosis (15 hips; five Stage I, 10 Stage II). With no Enoxaparin-related complications, 19 of 20 hips (95%) with primary osteonecrosis were unchanged from Stages I and II osteonecrosis at ≥ 108 weeks; 12 of 15 hips (80%) with secondary osteonecrosis progressed to Stages III and IV osteonecrosis. In primary osteonecrosis at ≥ 108 weeks, survival of 95% hips, or 76% (19/25 hips, based on intent to treat), compared favorably with untreated historical controls (approximately 20% 2-year survival), comparable to 20% survival in secondary hip osteonecrosis. Enoxaparin may prevent progression of primary hip osteonecrosis, decreasing the incidence of total hip replacement. Level of Evidence: Therapeutic study, II-1 (prospective cohort study)
Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders.

PURPOSE To determine the feasibility and efficacy of pharmacokinetic (PK) -based maintenance dosing of rituximab and possibly design a more rational maintenance schedule. PATIENTS AND METHODS Patients with CD20-positive lymphoproliferative disorders were treated with four weekly infusions of rituximab 375 mg/m(2). All patients without progressive disease were then monitored for 1 year and received a single infusion of 375 mg/m(2) when the level decreased below 25 microg/mL. RESULTS Twenty-nine of 31 patients were assessable with a variety of histologic subtypes. The overall response rate (ORR) for the entire group was 59% with 27% complete responses (CRs) and 32% partial responses. The median PFS for all patients was 19 months, with a median follow-up of 25 months. In 22 patients with low-grade non-Hodgkin's lymphoma (LGNHL), the ORR was 63% with 36% CR and median progression-free survival (PFS) has not been reached. Of 29 assessable patients, 22 were available for PK-based maintenance. The median time to repeat bolus was 5 months (range, 1 to 9 months) for the first, 3.5 months (range, 2 to 5 months) for the second, and 3 months (range, 2 to 4 months) for the third infusion. Ninety-five percent of patients required three or fewer infusions to be maintained in the therapeutic range. CONCLUSION Individualized PK dosing for rituximab produced efficacy comparable to other published maintenance strategies. PK data from this trial suggest that a rational maintenance strategy in patients with LGNHL would be a single dose of 375 mg/m(2) of rituximab every 3 to 4 months.
A Video-Assisted Thoracoscopic Approach to Transaxillary First Rib Resection

Objective Thoracic outlet syndrome (TOS) can be associated with neurologic, arterial, or venous deficiencies. When nonsurgical treatment has failed to adequately palliate TOS, surgical intervention is indicated. The supraclavicular and transaxillary approaches are currently the most commonly used approaches for first rib resection, yet little has been reported to date on outcomes of minimally invasive procedures, such as video-assisted thoracoscopic surgery (VATS). The purpose of this article was to describe a minimally invasive approach to TOS and the associated outcomes. Methods This study is a retrospective analysis of a prospectively maintained database. Patients who failed nonsurgical therapy for TOS were referred to our practice for evaluation of surgery with a VATS minimally invasive first rib resection. Between 2001 and 2010, 66 VATS procedures were performed on 58 patients (41 women, 17 men). Patients were followed postoperatively for a mean time of 13.5 months. Results Forty-one patients were women (70.7%), and the mean age was 40.5 years, with a patient age range of 17 to 59 years. The mean length of hospital stay was 2.47 days; median length of stay was 2 days. There were a total of eight complications (12.1%). There were no mortalities. Conclusions Video-assisted thoracoscopic surgery first rib resection for TOS is another feasible option for TOS, which can be added to the armamentarium of the thoracic surgeon. The outcomes associated with our technique are comparable with the outcomes related to other current standards of care.
Increased apoptosis of bone marrow CD34+ cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus

The changes in bone marrow (BM) stem cell reserve and function and stromal cell function in patients with active systemic lupus erythematosus (SLE) were investigated. The study was carried out on seven SLE patients and 28 healthy controls using flow cytometry and in vitro cell culture assays. We found that patients had low CD34+ cells, compared with the control group, reflecting the decrease of both CD34+/CD38− and CD34+/CD38+ cells. Patient CD34+/Fas+ but not CD34−/Fas+ cells were significantly increased. Apoptotic (7AADdim) cells were higher among CD34+/Fas+ than among CD34+/Fas− cells, and individual values of apoptotic CD34+ cells strongly correlated with the number of CD34+/Fas+ cells. These findings are suggestive of a Fas‐mediated apoptosis accounting for the low CD34+ cells in SLE patients. Moreover, we found that patients had low numbers of granulocyte‐macrophage colony‐forming units (CFU‐GM) and erythroid burst‐forming units (BFU‐E), compared with the control group, and that the generation of colony‐forming cells in long‐term BM cultures was significantly reduced. Patient BM stroma failed to support allogeneic progenitor cell growth. In one patient, CD34+ cells were increased, apoptotic CD34+/Fas+ cells were normalized and defective stromal cell function was restored after autologous stem cell transplantation. We concluded that defective haemopoiesis in SLE patients is probably caused, at least in part, to the presence of autoreactive lymphocytes in BM.
Survey about the knowledge of the HIV infection amongst recruits of the German military.

AIMS In the complex organizational unit of the German military (Bundeswehr), certain social conflicts and tensions may occur because of potential extreme situations and specific areas of conflict. The aim of this study was to obtain information from German military recruits regarding their knowledge of and behavioral patterns on the subject of HIV/AIDS. METHODS 219 Soldiers in the military barracks in the state of Rhineland-Palatinate (Germany) were surveyed by means of a questionnaire (return rate 96.8%). The questionnaire comprised the following subjects: level of and requirements for information, fear of infection, behavioral pattern when in contact with HIV-infected persons as well as attitude towards governmental regulations. RESULTS 4% of the surveyed soldiers considered their own knowledge about the subject of HIV/AIDS to be very good, 44% as good, 41% as sufficient and 7% as insufficient. 74% considered education to be necessary, and 26% felt it was not necessary. 68% of the surveyed subjects indicated that their protection of choice against infection was fidelity in partnership. 25% were of the opinion that an HIV-infected soldier should be discharged from military services and almost 20% supported that the entire barracks should be informed of such a case. 61% of those who were in favor of an obligatory registration by name (36%) also supported continued observation of the person infected with HIV. According to the surveyed soldiers, certain groups such as blood donors (86%), medical personnel (71%) as well as enlisted soldiers (28%) should receive mandatory testing. CONCLUSION The relatively broad spectrum of opinions indicated the necessity to offer sound information and raised the question of an official regulation.
Macrolide-lincosamide-streptogramin B resistance in Staphylococcus lentus results from the integration of part of a transposon into a small plasmid

The 8.0-kb macrolide-lincosamide-streptogramin B resistance plasmid pSES20 from Staphylococcus lentus harbored part of a Tn917-like transposon including the left terminal repeat, a gene almost identical to ermB, and its regulatory region, as well as the internal direct repeat. Homology between pSES20 and Tn917 ended at a sequence closely related to those of the resolution sites of Tn917 and Tn552 and staphylococcal recombination sites.
Prediction of patient outcome from Acinetobacter baumannii bacteremia with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores.

OBJECTIVE Acinetobacter baumannii is an important nosocomial pathogen associated with a high mortality rate. However, no objective and quantitative severity scores are available for the severity stratification. We aimed to assess the effectiveness of SOFA and APACHE II scores calculated at the onset of bacteremia in predicting the mortality of patients with A. baumannii bacteraemia. PATIENTS AND METHODS A total of 110 patients with A. baumannii bacteremia were included in this retrospective study during the 40-month study period. Information including clinical and laboratory data was collected. RESULTS Multivariate analysis showed that both SOFA and APACHE II scores were independent outcome predictors after adjustment for other parameters. Goodness-of-fit was good for SOFA and APACHE II, and both models displayed excellent AUROCs (SOFA: 0.83 ± 0.06, APACHE II: 0.82 ± 0.08 in predicting 14-day mortality; SOFA: 0.85 ± 0.04, APACHE II: 0.81 ± 0.04 in predicting in-hospital mortality). There was no significant difference in the predictions of the two scoring systems, and the scores were highly correlated (r(2)=0.724, p <0.001). We found that SOFA >8, APACHE II >29 and SOFA >7, APACHE II >23 are associated with significantly higher 14-day and in-hospital mortality rates, respectively. CONCLUSION SOFA and APACHE II scores assessed at the onset of bacteremia are reliable risk stratifying tools in predicting 14-day and in-hospital mortality in A. baumannii bacteremia. For ease of calculation, the use of SOFA rather than APACHE II score to predict mortality of A. baumannii bacteremia might have clinical application.
Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice

Abstract Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4+ T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action – in the context of T-cell immunity – that seemed to be dose dependent in the early immunopathogenesis of a MLDSTZ-induced model of T1D.
Growth-rate-dependent expression and cloning of gnd alleles from natural isolates of Escherichia coli

6-Phosphogluconate dehydrogenase (6PGD), encoded by gnd, is highly polymorphic among isolates of Escherichia coli form natural populations. As a means of characterizing the growth-rate-dependent regulation of the level of 6PGD, five gnd alleles, including the E. coli B/r allele, were crossed into E. coli K-12 with bacteriophage P1. In each of the isogenic strains, the level of 6PGD was two- to threefold higher in cells grown on glucose than in cells grown on acetate. The level of enzyme activity in the acetate-grown cells varied about sixfold within the set of isogenic strains. The physiological importance of these differences in enzyme level is discussed. The gnd gene was cloned from five E. coli strains and Salmonella typhimurium LT-2 and mapped with twelve restriction endonucleases. gnd was located and oriented on the chromosomal DNAs. The restriction maps of the genes were aligned at conserved restriction sites, and the relative divergence of the genes was estimated from restriction site polymorphisms. The E. coli gnd genes differed from the S. typhimurium gene by about 11%. Most of the E. coli genes differed from one another by less than 5%, but one allele differed from the others by about 10%. Only the gnd gene from E. coli K-12 had an IS5 element located nearby.
Evaluating the impact of imputations for missing participant outcome data in a network meta-analysis

Background In a meta-analysis of trials with missing outcome data, a parameter known as informative missing odds ratio (IMOR) can be used to quantify the relationship between informative missingness and a binary outcome. IMORs also account for the increased uncertainty due to missingness in the meta-analysis results. Purpose To extend the idea of IMOR into a network meta-analysis (NMA) setting in order to explore the impact of missing outcome data on the inferences about the relative effectiveness of several competing treatments in psychiatric trials. Methods IMORs were estimated in two datasets comparing anti-manic treatments and antidepressants. The outcome was response to treatments. In the original meta-analyses, missing participants were assumed to have failed regardless the treatment they were allocated to. To evaluate the robustness of this assumption in each dataset, several imputations of the missing outcomes were studied by an IMOR parameter in the NMA model. By comparing the odds ratios for efficacy under the initial analysis and under several assumptions about the missingness, we assessed the consistency of the conclusions. The missing data mechanism was studied by comparing the prior with the posterior IMOR distribution. Models were fitted using Markov chain Monte Carlo (MCMC) in WinBUGS. Results In both datasets, the relative effectiveness of the treatments seems to be affected only by the two extreme imputation scenarios of worst- and best-case analyses. Moreover, heterogeneity increases in both datasets under these two extreme scenarios. Overall, there is a non-significant change on the ranking of the anti-manic and antidepressant treatments. The posterior and prior IMOR distributions are very similar showing that the data do not provide any information about the true outcome in missing participants. There is a very weak indication that missing participants tend to fail in placebo and paroxetine, while the opposite occurs for sertraline, fluoxetine, and fluvoxamine. Limitations Investigation of informative missingness was limited two classes of treatments and for dichotomous outcome measures. The proportion of missing outcomes was very low overall, and hence, the power of detecting any differences in effectiveness estimated under the various imputation methods is small. Conclusions Sensitivity analysis to account for missing outcome data and their uncertainty in the NMA can be undertaken by extending the idea of IMOR. In two case examples, we found no differences between the various models due to low missing data rate. In line with previous observations, data carry little information about the reason of missingness.
Ghrelin stimulation by hypothalamic–pituitary–adrenal axis activation depends on increasing cortisol levels

Ghrelin plasma concentration increases in parallel to cortisol after a standardized psychological stress in humans, but the physiological basis of this interaction is unknown. We aimed to elucidate this question by studying the ghrelin response to pharmacological manipulation of the hypothalamic–pituitary–adrenal (HPA) axis. Six lean, healthy male volunteers were examined under four experimental conditions. Blood samples were collected every 30 min for two sequential periods of two hours. Initially, a baseline period was followed by intravenous injection of a synthetic analog of ACTH (250 μg). Subsequently, a single dose of metyrapone was administered at midnight and in the following morning, blood samples were collected for 2 h, followed by an intravenous injection of hydrocortisone (100 mg) with continued sampling. We show that increased cortisol serum levels secondary to ACTH stimulation or hydrocortisone administration are positively associated with plasma ghrelin levels, whereas central stimulation of the HPA axis by blocking cortisol synthesis with metyrapone is associated with decreased plasma ghrelin levels. Collectively, this suggests that HPA-axis-mediated elevations in ghrelin plasma concentration require increased peripheral cortisol levels, independent of central elevation of ACTH and possibly CRH levels.