Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Enzyme Immunoassays and PCR for Detection ofHelicobacter pylori in Stool Specimens from Pediatric Patients before and after Eradication Therapy

ABSTRACT This study of pediatric patients was intended to determine the suitability of stool PCR and two antigen enzyme immunoassays (EIAs; Premier Platinum HpSA and the novel FemtoLab H. pylori), which detectHelicobacter pylori antigens in feces, as pretreatment diagnostic tools and especially as posttreatment control. Forty-nineH. pylori-infected children with dyspepsia received eradication therapy. Successful treatment was determined by a negative [13C]urea breath test 4 and 12 weeks after discontinuation of therapy. Fecal specimens were collected prior to eradication therapy as well as 4 weeks after the end of treatment. Successfully treated children delivered stool samples at 6, 8, and 12 weeks posttreatment also. Specimens were examined by seminested PCR and Premier Platinum HpSA and were reexamined by both EIAs as soon as FemtoLab H. pylori was available. In the first test series, the overall sensitivities of PCR and Premier Platinum HpSA were 93.0 and 91.1%, respectively. With specimens collected at 4 weeks after treatment, the respective specificities were 68.8 and 79.3%. After longer follow-up periods, however, they gradually increased to 100 and 96.9%, respectively. In the new test series, Premier Platinum HpSA delivered a considerably lower number of false-positive results (4 versus 18), indicating intertest variations. The overall test sensitivity was 94.6%, and the overall specificity was 97.5%. FemtoLab H. pylori showed an excellent performance with an overall sensitivity and specificity of 98.2 and 98.1%, respectively. Thus, in contrast to PCR, both EIAs were shown to be suitable for early posttreatment control.
Changing clinical features of coeliac disease

The classical clinical picture of coeliac disease includes prolonged diarrhoea with failure to thrive. During the past two decades this type of active presentation of coeliac disease has decreased in many European countries, giving the impression that coeliac disease is a disappearing disease. However, this is not true. The disease can be found in older children with a more or less silent presentation. Silent coeliac disease can be detected by active screening with serological tests. Coeliac disease can be suspected in children suffering from mild gastrointestinal symptoms, such as abdominal pain, and in those with signs of nutritional deficiencies, as well as in children of first‐degree relatives of already diagnosed coeliacs, patients with IgA‐deficiency, patients suffering from dental enamel hypoplasia or dermatitis herpetiformis, and patients with some other disease known to be associated with coeliac disease, such as diabetes mellitus. According to the fundamental criteria of coeliac disease, the intestinal mucosa is flat when the individual is eating gluten‐containing foods. However, this is not strictly true. Intolerance to gluten is obviously variable and the intestinal mucosa may be normal. This type of latent coeliac disease can be detected by analysing genetic markers, measuring antibodies in intestinal fluid or counting the density of intra‐epithelial gamma/delta T cells which are increased greatly even in the latent phase of coeliac disease. Thus the general concept of the natural history of coeliac disease is changing.
The novel autophagy inhibitor elaiophylin exerts antitumor activity against multiple myeloma with mutant TP53 in part through endoplasmic reticulum stress-induced apoptosis

ABSTRACT Elaiophylin is a natural compound and a novel and potent inhibitor of late stage autophagy with outstanding antitumor activity in human ovarian cancer cells. However, the possible biologic effects and functional linkage between elaiophylin and multiple myeloma (MM) have not been explored. This study aimed to assess the effect of elaiophylin on MM cells with mutant TP53 and the possible molecular mechanism. The results suggested that elaiophylin exerted anti-myeloma activity by inducing apoptosis and proliferation arrest. As expected, elaiophylin blocked autophagy flux in MM cells. Subsequently, persistent activation of endoplasmic reticulum (ER) stress was induced. Moreover, the apoptotic effect was to some extent attenuated by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Further studies indicated that elaiophylin effectively suppressed MM cell growth without obvious side effects in zebrafish embryo and mouse xenograft models. Taken together, our data are the first to demonstrate that exposure of human MM cells with mutant TP53 to elaiophylin blocked autophagy flux and thus induced cell death, which partially involved ER stress-associated apoptosis. Targeted disruption of the cellular protein handling system by elaiophylin is therefore a promising therapeutic strategy for overcoming incurable MM, even when TP53 mutations are present.
SELECTION FOR MECHANICAL ADVANTAGE UNDERLIES MULTIPLE CRANIAL OPTIMA IN NEW WORLD LEAF‐NOSED BATS

Selection for divergent performance optima has been proposed as a central mechanism underlying adaptive radiation. Uncovering multiple optima requires identifying forms associated with different adaptive zones and linking those forms to performance. However, testing and modeling the performance of complex morphologies like the cranium is challenging. We introduce a three‐dimensional finite‐element (FE) model of the cranium that can be morphed into different shapes by varying simple parameters to investigate the relationship between two engineering‐based measures of performance, mechanical advantage and von Mises stress, and four divergent adaptive zones occupied by New World Leaf‐nosed bats. To investigate these relationships, we tested the fit of Brownian motion and Ornstein–Uhlenbeck models of evolution in mechanical advantage and von Mises stress using dated multilocus phylogenies. The analyses revealed three performance optima for mechanical advantage among species from three adaptive zones: bats that eat nectar; generalized insectivores, omnivores and some frugivores; and bats that specialize on hard canopy fruits. Only two optima, one corresponding to nectar feeding, were consistently uncovered for von Mises stress. These results suggest that mechanical advantage played a larger role than von Mises stress in the radiation of New World Leaf‐nosed bats into divergent adaptive zones.
Central and peripheral autoantigen presentation in immune tolerance

Recent studies in both humans and experimental rodent models provide new insight into key mechanisms regulating tolerance to self‐molecules. These recent advances are bringing about a paradigm shift in our views about tolerance to self‐molecules with tissue‐restricted expression. There is, indeed, mounting evidence that selected antigen‐presenting cells (APCs) have the ability to synthesize and express self‐molecules, and that such expression is critical for self‐tolerance. Insulin is a key hormone produced exclusively by pancreatic β‐cells and a critical autoantigen in type 1 diabetes. It provides an excellent example of a molecule with tissue‐restricted expression that is expressed ectopically by APCs. The fact that APCs expressing insulin have been demonstrated in both thymus and peripheral lymphoid tissues suggests that they may play a role in insulin presentation in both the central and peripheral immune system. Experimental mice, in which insulin expression was altered, provide functional data that help to dissect the role of insulin presentation by APCs of the immune system. This review addresses recent literature and emerging concepts about the expression of self‐molecules in the thymus and peripheral lymphoid tissues and its relation to self‐tolerance.
Physical Therapists' Guideline Adherence on Early Mobilization and Intensity of Practice at Dutch Acute Stroke Units: A Country-Wide Survey

Background and Purpose— Clinical practice guidelines for patients with stroke recommend early stroke rehabilitation at acute hospital stroke units. The present study aimed to (1) explore the organization of early stroke rehabilitation; (2) investigate current practice with respect to early mobilization and augmented exercise therapy time; and (3) identify the perceived barriers to and facilitators for guideline adherence as reported by physical therapists (PTs) working on acute hospital stroke units. Methods— All 96 Dutch acute hospital stroke units were requested to assign one PT for participation in the survey. Results— Of the 96 contacted PTs, 91 returned the questionnaire. Seventy-one percent of acute hospital stroke units reported that out-of-bed mobilization of patients was performed within 24 hours. PTs provided a mean of 22 minutes of physical therapy per weekday and weekend therapy was not standard practice. PTs reported having sufficient knowledge of and experience with the clinical practice guidelines for patients with stroke and reported that the clinical practice guidelines for patients with stroke left enough room for them to draw their own conclusions and to take patient preferences into account. PTs perceived insufficient time to comply with the clinical practice guidelines for patients with stroke and a need for financial compensation to realize human resources. Conclusions— Our national survey among PTs suggests that the organization of early stroke rehabilitation varies considerably and that early mobilization and intensity of practice in early stroke rehabilitation are not optimal. Addressing this problem requires agreement between hospital management boards and insurance companies about minimum services and resources required and the introduction of novel methods of increasing duration of exercise therapy with minimal use of resources.
Intravenous thrombolysis for acute ischemic stroke: a bridge between two centuries

ABSTRACT Introduction: Intravenous tissue-plasminogen activator (tPA) remains the only approved systemic reperfusion therapy suitable for most patients presenting timely with acute ischemic stroke. Accumulating real-word experience for over 20 years regarding tPA safety and effectiveness led to re-appraisal of original contraindications for intravenous thrombolysis (IVT). Areas covered: This narrative review focuses on fast yet appropriate selection of patients for safe administration of tPA per recently expanded indications. Novel strategies for rapid patient assessment will be discussed. The potential for mobile stroke units (MSU) that shorten onset-to-needle time and increase tPA treatment rates is addressed. The use of IVT in the era of non-vitamin K antagonist oral anticoagulants (NOACs) is highlighted. The continuing role of IVT in large vessel occlusion (LVO) patients eligible for mechanical thrombectomy (MT) is discussed with regards to ‘drip and ship’ vs. ‘mothership’ treatment paradigms. Promising studies of penumbral imaging to extend IVT beyond the 4.5-hour window and in wake-up strokes are summarized. Expert commentary: This review provides an update on the role of IVT in specific conditions originally considered tPA contraindications. Novel practice challenges including NOAC’s, MSU proliferation and bridging therapy (IVT&MT) for LVO patients, and the potential extension of IVT time-window using penumbral imaging are emerging as safe and potentially effective IVT applications.
Effects of the Irish smoking ban on respiratory health of bar workers and air quality in Dublin pubs.

BACKGROUND Environmental tobacco smoke (ETS) causes disease in nonsmokers. Workplace bans on smoking are interventions to reduce exposure to ETS to try to prevent harmful health effects. On March 29, 2004, the Irish government introduced the first national comprehensive legislation banning smoking in all workplaces, including bars and restaurants. This study examines the impact of this legislation on air quality in pubs and on respiratory health effects in bar workers in Dublin. METHODS Exposure study. Concentrations of particulate matter 2.5 microm or smaller (PM(2.5)) and particulate matter 10 microm or smaller (PM(10)) in 42 pubs were measured and compared before and after the ban. Benzene concentrations were also measured in 26 of the pubs. Health effects study. Eighty-one barmen volunteered to have full pulmonary function studies, exhaled breath carbon monoxide, and salivary cotinine levels performed before the ban and repeated 1 year after the ban. They also completed questionnaires on exposure to ETS and respiratory symptoms on both occasions. FINDINGS Exposure study. There was an 83% reduction in PM(2.5) and an 80.2% reduction in benzene concentration in the bars. Health effects study. There was a 79% reduction in exhaled breath carbon monoxide and an 81% reduction in salivary cotinine. There were statistically significant improvements in measured pulmonary function tests and significant reductions in self-reported symptoms and exposure levels in nonsmoking barmen volunteers after the ban. CONCLUSIONS A total workplace smoking ban results in a significant reduction in air pollution in pubs and an improvement in respiratory health in barmen.
Performance of limited feedback secure MISO systems in temporally correlated channels

We consider the problem of secure communication with multiple antenna transmission in temporally correlated channels. In order to achieve a secrecy gain, a channel state information of the intended receiver at the transmitter is required. In this work, we present a limited feedback link by employing differential codebook which utilizes the temporal correlation properties of the wireless channels for a secure multi-antenna system. The secrecy performances are shown for different channel correlations.
Binocular depth discrimination and the nasotemporal division

1. If classical partial decussation exactly segregates the projections of right and left hemi‐retinae on to the two optic tracts, the images of an object in central vision, nearer or further than the fixation point, should project to separate hemispheres. This would prevent the encoding of retinal disparity by binocularly driven neurones of the visual cortex.
ErbB‐2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer.

Overexpression of the erbB‐2 gene contributes to aggressive behavior of various human adenocarcinomas, including breast cancer, through an unknown molecular mechanism. The erbB‐2‐encoded protein is a member of the ErbB family of growth factor receptors, but no direct ligand of ErbB‐2 has been reported. We show that in various cells ErbB‐2 can form heterodimers with both EGF receptor (ErbB‐1) and NDF receptors (ErbB‐3 and ErbB‐4), suggesting that it may affect the action of heterologous ligands without the involvement of a direct ErbB‐2 ligand. This possibility was addressed in breast cancer cells through either overexpression of ErbB‐2 or by blocking its delivery to the cell surface by means of an endoplasmic reticulum‐trapped antibody. We report that ErbB‐2 overexpression enhanced binding affinities to both EGF and NDF, through deceleration of ligand dissociation rates. Likewise, removal of ErbB‐2 from the cell surface almost completely abolished ligand binding by accelerating dissociation of both growth factors. The kinetic effects resulted in enhancement and prolongation of the stimulation of two major cytoplasmic signaling pathways, namely: MAP kinase (ERK) and c‐Jun kinase (SAPK), by either ligand. Our results imply that ErbB‐2 is a pan‐ErbB subunit of the high affinity heterodimeric receptors for NDF and EGF. Therefore, the oncogenic action of ErbB‐2 in human cancers may be due to its ability to potentiate in trans growth factor signaling.
DX 9065A a novel, synthetic, selective and orally active inhibitor of factor Xa: in vitro and in vivo studies.

DX 9065A is the first member of a newly developed series of synthetic and selective inhibitors of factor Xa. DX 9065A inhibited in a dose-dependent manner human factor Xa with K iota value of 3.1 +/- 0.5 nM. Steady-state studies revealed that DX 9065A was a competitive inhibitor of factor Xa. DX 9065A inhibited thrombin generation occurring via both the extrinsic and intrinsic pathway in vitro and in vivo. After i.v. injection to rabbits, DX 9065A displayed prolonged anti-factor Xa activity and inhibition of thrombin generation. Pretreatment of mice with DX 9065A dose-dependently improved the survival rate of mice injected with a lethal dose of tissue factor (ED50 = 1.1 +/- 0.2 mg/kg). After p.o. administration, DX 9065A caused a reduction in tissue factor-induced mortality of mice with ED50 value of 56 +/- 7 mg/kg. When given i.v. to rats, DX 9065A exhibited a dose-dependent antithrombotic effect against factor Xa + stasis-induced venous thrombosis (ED50 = 1.2 +/- 0.7 mg/kg i.v.), but also in an arteriovenous shunt thrombosis model (ED50 = 8.1 +/- 3.5 mg/kg i.v.) without affecting bleeding time significantly. Similar effects were obtained after s.c. or p.o. administration. In rabbits, after i.v. , s.c. or p.o. administration, DX 9065A inhibited stasis-induced thrombosis after injection of tissue factor with ED50 values of 0.03 +/- 0.01, 0.3 +/- 0.07 and 50.5 +/- 19 mg/kg, respectively (n = 10). DX 9065A inhibited in a dose-dependent manner endotoxin-induced venous thrombosis in the rabbit (ED50 = 0.25 +/- 0.1 mg/kg i.v.) (n = 5) and reduced the decrease in platelet number and circulating fibrinogen levels in an experimental model of tissue factor-induced disseminated intravascular coagulation. Compared to standard heparin, DX 9065A exhibited a favorable antithrombotic/bleeding ratio, therefore showing that it might be considered as a promising compound in the treatment and prevention of various thrombotic diseases.
Crestal bone changes in macrogeometrically similar implants with the implant-abutment connection at the crestal bone level or 2.5 mm above: a prospective randomized clinical trial.

OBJECTIVE Crestal bone loss around dental implants is a criterion for success as this could prevent loss of implant and superstructure. The macrogeometry of the implant could influence bone remodelling when the implant-abutment connection is placed at crestal bone level or above. The aim of this study was to evaluate crestal bone remodelling in a randomized clinical prospective trial in macrogeometrically similar implants with the prosthetic connection at the crestal bone level and 2.5 mm above. The null hypothesis was that there was no difference in crestal bone loss after 1 year of early loading. MATERIAL AND METHODS Patients were referred to Academic Centre of Dentistry Amsterdam for implant placement. Patients were subjected to inclusion and exclusion criteria and received a minimum of two implants: an implant with the prosthetic abutment connection at the crestal bone level (minimized collar [MC], bone level) and one with the prosthetic abutment connection 2.5 mm supracrestal (long collar [LC], tissue level). The mesial or distal location of each implant type was blinded for the patient and randomized. The implants were loaded splinted after 3 weeks of healing. The primary outcome was bone-level change assessed after 1 year of loading. RESULTS Thirty-three patients fulfilled the inclusion criteria. Thirty-nine Thommen SPI ELEMENT LC implants and 39 MC were placed, and each fixed dental prosthesis was supported by one LC and one MC implant. The intraclass correlation of measures performed by the first and second X-ray examiner was as follows: on the mesial side of the MC implant 0.990 (0.980-0.995; 95% confidence interval [CI]), 0.980 (0.962-0.990; 95% CI) on the distal side of the MC implant, 0.979 (0.959-0.989; 95% CI) and 0.988 (0.978-0.994; 95% CI) on the mesial and distal side of the LC implant, respectively. The mean bone loss of the MC implant was 0.4 ± 0.4 mm. The mean bone loss of the LC implant was 0.2 ± 0.5 mm. The paired samples t-test showed a statistically significant difference (P < 0.05) between the MC and LC implants. CONCLUSION Dental implants at bone level show statistically significantly (P < 0.05) more crestal bone change after 1 year of loading than a tissue-level implant.
Prolonged disease‐free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external‐beam irradiation plus bolus fluorouracil (5‐FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5‐FU. 5‐FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early‐stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow‐up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease‐free and overall survival in highly selected patients with early‐stage cholangiocarcinoma.