Miracle-dz/UniFAR-FTUs huggingface dataset:
Blunt atrial transseptal puncture using excimer laser in swine

Objectives: We describe a new approach that may enhance safety of atrial transseptal puncture using a commercially available laser catheter that is capable of perforation only when energized. We test this approach in swine. Background: Despite wide application, conventional needle transseptal puncture continues to risk inadvertent nontarget perforation and its consequences. Methods: We used a commercial excimer laser catheter (0.9‐mm Clirpath, Spectranetics). Perforation force was compared in vitro with a conventional Brockenbrough needle. Eight swine underwent laser transseptal puncture under X‐ray fluoroscopy steered using a variety of delivery catheters. Results: The 0.9‐mm laser catheter traversed in vitro targets with reduced force compared with a Brockenbrough needle. In vitro, the laser catheter created holes that were 25–30% larger than the Brockenbrough needle. Laser puncture of the atrial septum was successful and accurate in all animals, evidenced by oximetry, pressure, angiography, and necropsy. The laser catheter was steered effectively using a modified Mullins introducer sheath and using two different deflectable guiding catheters. The mean procedure time was 15 ± 6 min, with an average 3.0 ± 0.8 sec of laser activation. There were no adverse sequelae after prolonged observation. Necropsy revealed discrete 0.9‐mm holes in all septae. Conclusion: Laser puncture of the interatrial septum is feasible and safe in swine, using a blunt laser catheter that perforates tissues in a controlled fashion. © 2007 Wiley‐Liss, Inc.
Lung Transplantation in Patients with Pretransplantation Donor-Specific Antibodies Detected by Luminex Assay

Background New methods of solid-phase assays, such as Luminex assay, with high sensitivity in detecting anti–human leukocyte antigen (HLA) antibodies (Abs), have increased the proportion of sensitized candidates waiting for lung transplantation (LTx). However, how to apply these results clinically during graft allocation is debated: strict exclusion of candidates with Luminex-positive results can lead to lost opportunities for Tx. We retrospectively analyzed the clinical impact of pre-LTx Luminex-detected Abs on post-LTx outcomes for patients who underwent LTx before the availability of Luminex assay. Methods We analyzed data for 56 successive patients who underwent LTx before 2008 and were considered to not have anti-HLA Abs by then-available methods of detection at the date of their LTx. Pre-LTx sera from these patients were retested by Luminex assay. Using log-rank test, freedom from bronchiolitis obliterans syndrome (BOS) and graft survival were compared between patients with and without pre-LTx Luminex-detected anti-HLA Abs classes I and II and donor-specific Abs (DSA) classes I and II. Results Freedom from bronchiolitis obliterans syndrome was lower, and mortality was higher for patients with than those without pre-LTx Luminex-detected DSA class II (P=0.004 and P=0.007, respectively) but did not differ for patients with and without DSA class I or anti-HLA Abs class I or II. Conclusions It suggests to avoid attributing graft with forbidden antigens to sensitized candidates with Luminex-detected DSA class II and to evaluate the role of specific posttransplantation protocols for LTx candidates who require emergency LTx.
Advances in Mediation Analysis Can Facilitate Nursing Research

Background:Two recent advances in the statistical methods for testing hypotheses about mediation effects are important for nursing science. First, bootstrap sampling distributions provide more accurate tests of hypotheses about mediated effects. Second, methods for testing statistical hypotheses about subgroup differences in mediation models (moderated mediation) are now well developed. Objective:The aims of this study were to demonstrate the use and relatively simple computation of bootstrap sampling distributions in tests of mediation effects and to demonstrate a recently refined method for testing hypotheses about moderated mediation. Method:Using hypothetical data, a step-by-step demonstration was provided of the construction of a bootstrap sampling distribution for a correlation coefficient. Then, tests of mediation and moderated mediation were demonstrated using data from a clinical trial of an intervention for caregivers of patients with Parkinson's disease or Alzheimer's disease. In a model hypothesizing that mutuality between caregiver and care recipient mediates the effect of objective on subjective levels of caregiver burden, the bootstrap sampling distribution was calculated of the mediation effect and, from that, two types of 95% confidence intervals for it. Then the hypothesis was tested that the mediating effect of mutuality was stronger for caregivers of patients with Parkinson's disease than for caregivers of patients with Alzheimer's disease. Conclusions:Statistical hypothesis testing should never dictate all conclusions. However, the statistical advances in mediation analysis described here will facilitate nursing research as both nurse scientists and methodologists understand their assumptions and logic.
Identification of P‐glycoprotein substrates and inhibitors among psychoactive compounds — implications for pharmacokinetics of selected substrates

The pharmacokinetics of antipsychotic drugs has become an integral part in understanding their pharmacodynamic activity and clinical effects. In addition to metabolism aspects, carrier‐mediated transport, particularly secretion by ABC transporters, has been discussed as potentially relevant for this group of therapeutics. In this study, the psychoactive compounds perphenazine, flupentixol, domperidone, desmethyl clozapine, haloperidol, fluphenazine, fluvoxamine, olanzapine, levome‐promazine, perazine, desmethyl perazine, clozapine, quetiapine and amisulpride were characterized in terms of P‐glycoprotein (P‐gp) affinity and transport. Experimental methods involved a radioligand displacement assay with [3H]talinolol as radioligand and transport — as well as transport inhibition — studies of the P‐gp substrate [3H]talinolol across Caco‐2 cell monolayers. In addition, the physicochemical descriptors log P and Δlog P were determined to test potential correlations between transporter affinity and lipophilicity parameters. All of the tested antipsychotics showed affinity to P‐gp albeit their IC50 values (concentration of competitor that displaced 50% of the bound radioligand) differed by a factor exceeding 1000, when compared using the transport inhibition assay. From the group of P‐gp substrates, amisulpride and fluphenazine were selected for in‐vivo drug‐drug interaction studies in rats to demonstrate the in‐vivo relevance of the in‐vitro findings. Compounds were administered by intraperitoneal injection either alone or in combination with 50 mg kg−1 ciclosporin. The concentration versus time profiles for both drugs were followed in serum as well as in brain tissues. Significant differences between the treatments with the antipsychotic alone versus the combination of antipsychotic with ciclosporin were found for amisulpride. The distribution of amisulpride to the brain was increased and systemic serum levels were likewise increased indicating decreased systemic clearance for the combination regimen. For fluphenazine, systemic levels with and without co‐administraton of ciclosporin were comparable while higher brain‐to‐serum concentration ratios were found after co‐administration of ciclosporin. The findings are explained on the basis of the limited contribution of P‐gp‐mediated transport to the elimination of fluphenazine and to a direct effect with respect to its distribution into the brain.
The global burden of hepatitis E virus genotypes 1 and 2 in 2005

We estimated the global burden of hepatitis E virus (HEV) genotypes 1 and 2 in 2005. HEV is an emergent waterborne infection that causes source‐originated epidemics of acute disease with a case fatality rate thought to vary by age and pregnancy status. To create our estimates, we modeled the annual disease burden of HEV genotypes 1 and 2 for 9 of 21 regions defined for the Global Burden of Diseases, Injuries, and Risk Factors Study (the GBD 2010 Study), which represent 71% of the world's population. We estimated the seroprevalence of anti‐HEV antibody and annual incidence of infection for each region using data from 37 published national studies and the DISMOD 3, a generic disease model designed for the GBD Study. We converted incident infections into three mutually exclusive results of infection: (1) asymptomatic episodes, (2) symptomatic disease, and (3) death from HEV. We also estimated incremental cases of stillbirths among infected pregnant women. For 2005, we estimated 20.1 (95% credible interval [Cr.I.]: 2.8‐37.0) million incident HEV infections across the nine GBD Regions, resulting in 3.4 (95% Cr.I.: 0.5‐6.5) million symptomatic cases, 70,000 (95% Cr.I.: 12,400‐132,732) deaths, and 3,000 (95% Cr.I.: 1,892‐4,424) stillbirths. We estimated a probability of symptomatic illness given infection of 0.198 (95% Cr.I.: 0.167‐0.229) and a probability of death given symptomatic illness of 0.019 (95% Cr.I.: 0.017‐0.021) for nonpregnant cases and 0.198 (95% Cr.I.: 0.169‐0.227) for pregnant cases. Conclusion: The model was most sensitive to estimates of age‐specific incidence of HEV disease. (HEPATOLOGY 2012)
The expression of E-cadherin and catenins in sporadic colorectal carcinoma.

The E-cadherin/catenin complex plays a major role in epithelial cell-cell adhesion. Immunohistochemical studies have highlighted perturbation in the expression and distribution of E-cadherin and catenins in sporadic colorectal neoplasms. In this study, we compared the expression of E-cadherin and catenins (alpha-, beta-, and gamma-catenin) in 30 sporadic colorectal carcinomas with that in the adjacent nonneoplastic mucosa and assessed whether any perturbation in the level of expression occurred at the messenger RNA (mRNA) or protein level. We also compared the expression of E-cadherin and catenins in 13 lymph node deposits and the primary tumors. Immunohistochemistry was used to study the level of expression and cellular distribution of E-cadherin and catenins. Levels of mRNA were studied by in situ hybridization. E-cadherin and catenin immunoreactivity was increased with cytoplasmic accumulation in more than 85% of the neoplasms. There were marked increases in the levels of mRNA in the carcinomas compared with the nonneoplastic mucosa. Nuclear localization of beta-catenin was higher at the invasive margin of some tumors, but expression of E-cadherin and catenin transcripts in the lymph node deposits showed no consistent relationship to that in the primary tumors.
Temperature and inoculation method influence disease phenotypes and mortality of Eucalyptus marginata clonal lines inoculated with Phytophthora cinnamomi

Survival of l-year-old plants of three clonal lines of Eucalyptus marginata (jarrah), two ranked as resistant (RR1 and RR2) and one as susceptible (SS1) to Phytophthora cinnamomi, was assessed after pathogen inoculation with either mycelial mats underbark or zoospores on the stem. Plants were grown at 15,20, 25 and 30°C. Method of inoculation did not produce comparable mortalities of the clonal lines, particularly at 25 and 30°C. At these temperatures, all three clonal lines had 100% mortality when inoculated underbark, but when inoculated with zoospores, RR1 had 60% survival and lines SS1 and RR2 had 100% mortality. Generally, the level of resistance of all clonal lines declined with increasing temperature. RR2 had consistently higher mortality than SS1, and is therefore not considered resistant. Lesion development was also measured in detached stems of RR1 and a susceptible clonal line (SS2) each inoculated underbark with four different P. cinnamomi isolates. Stems were assessed for lesion development at 20, 25 and 30°C for 4 days. For all four isolates, detached stems of RR1 generally had smaller lesions than those of SS2, particularly at 30°C. The increase in lesion length with increasing temperature was greatest for SS2. Detached stems may have potential in screening for jarrah resistant to P. cinnamomi and allow identification of susceptible clonal lines at 30°C.
The older persons' assessment and liaison team 'OPAL': evaluation of comprehensive geriatric assessment in acute medical inpatients.

BACKGROUND Reducing hospital length of stay (LOS) in older acute medical inpatients is a key productivity measure. Evidence-based predictors of greater LOS may be targeted through Comprehensive Geriatric Assessment (CGA). OBJECTIVE Evaluate a novel service model for CGA screening of older acute medical inpatients linked to geriatric intervention. SETTING Urban teaching hospital. SUBJECTS Acute medical inpatients aged 70+ years. INTERVENTION Multidisciplinary CGA screening of all acute medical admissions aged 70+ years leading to (a) rapid transfer to geriatric wards or (b) case-management on general medical wards by Older Persons Assessment and Liaison team (OPAL). METHODS Prospective pre-post comparison with statistical adjustment for baseline factors, and use of national benchmarking LOS data. Pre-OPAL (n = 46) and post-OPAL (n = 49) cohorts were similarly identified as high-risk by the CGA screening tool, but only post-OPAL patients received the intervention. RESULTS Pre-OPAL, 0% fallers versus 92% post-OPAL were specifically assessed and/or referred to a falls service post-discharge. Management of delirium, chronic pain, constipation, and urinary incontinence similarly improved. Over twice as many patients were transferred to geriatric wards, with mean days from admission to transfer falling from 10 to 3. Mean LOS fell by 4 days post-OPAL. Only the OPAL intervention was associated with LOS (P = 0.023) in multiple linear regression including case-mix variables (e.g. age, function, 'geriatric giants'). Benchmarking data showed the LOS reduction to be greater than comparable hospitals. CONCLUSION CGA screening of acute medical inpatients leading to early geriatric intervention (ward-based case management, appropriate transfer to geriatric wards), improved clinical effectiveness and general hospital performance.
The N-terminal Phosphodegron Targets TAZ/WWTR1 Protein for SCFβ-TrCP-dependent Degradation in Response to Phosphatidylinositol 3-Kinase Inhibition*

Background: TAZ overexpression is implicated in cancer development. Results: The N-terminal phosphodegron is phosphorylated by GSK3, which creates a binding site for β-TrCP, resulting in TAZ ubiquitylation and degradation. Conclusion: The N-terminal phosphodegron regulates TAZ stability in response to the dysregulated PI3K pathway. Significance: Our study reveals the underlying mechanism of TAZ N-terminal phosphodegron regulation in elevated TAZ cancers with a dysregulated PTEN/PI3K pathway. The Hippo tumor suppressor pathway plays a major role in development and organ size control, and its dysregulation contributes to tumorigenesis. TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1) is a transcription co-activator acting downstream of the Hippo pathway, and increased TAZ protein levels have been associated with human cancers, such as breast cancer. Previous studies have shown that TAZ is inhibited by large tumor suppressor (LATS)-dependent phosphorylation, leading to cytoplasmic retention and ubiquitin-dependent degradation. The LATS kinase, a core component of the Hippo pathway, phosphorylates the C-terminal phosphodegron in TAZ to promote its degradation. In this study, we have found that the N-terminal phosphodegron of TAZ also plays a role in TAZ protein level regulation, particularly in response to different status of cellular PI3K signaling. GSK3, which can be inhibited by high PI3K via AKT-dependent inhibitory phosphorylation, phosphorylates the N-terminal phosphodegron in TAZ, and the phosphorylated TAZ binds to β-TrCP subunit of the SCFβ-TrCP E3 ubiquitin ligase, thereby leading to TAZ ubiquitylation and degradation. We observed that the TAZ protein level is elevated in tumor cells with high PI3K signaling, such as in PTEN mutant cancer cells. This study provides a novel mechanism of TAZ regulation and suggests a role of TAZ in modulating tissue growth and tumor development in response to PI3K signaling.
The accessory optic system of rabbit. II. Spatial organization of direction selectivity.

1. To compare the spatial organization of the direction selectivity of neurons in the medial terminal nucleus (MTN) of the accessory optic system with that of neurons in the adjacent ventral tegmentum, extracellular single-unit recordings were made in the anesthetized rabbit. The ventral tegmental neurons were located in a region called the visual tegmental relay zone (VTRZ), which is defined by the ventral tegmental terminal field of contralaterally projecting MTN neurons. 2. Some of the present sample of MTN neurons (5 of 34) had monocular receptive fields composed of two parts distinguished by a marked difference in the orientation of their respective direction-selective tuning curves. For one part of the receptive field the preferred excitatory direction was "up," while for the other part it was "down. " Such receptive fields for one eye were called bipartite, whereas the more usually encountered MTN receptive fields, which could be characterized by a single direction-selective tuning curve, were called uniform. 3. Of the 16 neurons recorded from the VTRZ, all but one were binocular. For these neurons, both uniform and bipartite receptive fields were found for each eye alone. The only monocular neuron encountered in the VTRZ had a contralateral, bipartite receptive field. 4. The spatial organization of the direction selectivity of bipartite receptive fields strongly suggests that they are suited to represent rotation of the visual field about a horizontal axis located in the vertical plane that divides the receptive field into two parts. 5. The boundary between the two parts of the bipartite receptive fields was found using handheld visual stimuli at one of two azimuthal locations, either close to 45 degrees or between 95 and 125 degrees (the 0 degree reference was rostral in the midsagittal plane). This particular structure of the bipartite receptive fields suggests that their preferred rotation axes have a close spatial relation to the best-response axes of the semicircular canals. 6. Seven VTRZ neurons were antidromically activated by electrical stimulation of the ipsilateral dorsal cap of the inferior olive. Since the receptive fields of VTRZ neurons have many of the structural features characteristic of the receptive fields of rostral dorsal cap neurons we conclude that the spatial organization of the receptive fields of dorsal cap neurons is, for the most part, synthesized prior to the inferior olive. (ABSTRACT TRUNCATED AT 400 WORDS)
A capacitor voltage balancing method with zero-voltage switching for split phase inverter

This paper presents a new method of current control that employs burst mode in order to balance the dc-side capacitor voltages of split phase inverters. By alternating the inductor current in every switching period, zero-voltage switching (ZVS) can be achieved, which avoids the reverse recovery issue of power MOSFETs. As a result, super-junction MOSFETs instead of IGBTs can be employed to achieve higher efficiency. Combining the hysteresis current control with traditional pulse-width modulation (PWM), a new burst mode control method is proposed in this paper. The minimum operation time during a set modulation period is limited then the efficiency at the light load can be increased. A buck-and-boost converter is employed as the auxiliary circuit for the capacitor voltage balancing circuit. Due to the proposed ZVS method, inductor volume can be reduced. A prototype with 25 A current capacity is built to verify all the performance of the presented control method. The efficiency over the whole load range is over 98% with a peak efficiency of 98.4%.
Efficacy and Tolerance of Infliximab in Children and Adolescents with Crohn’s Disease

Infliximab, a monoclonal antibody against tumor necrosis factor-alpha, has been shown to be effective for the treatment of refractory Crohn’s disease in adult patients, but experience in pediatrics is limited. This retrospective study included 88 children and adolescents, 39 girls and 49 boys, with a median age of 14 years (range 3.3–17.9). Infliximab was indicated for active disease (66%) and/or fistulas (42%) that were refractory to corticosteroids (70%), and/or other immunosuppressive (82%) agents, and/or parenteral nutrition (20%). Patients received 1 to 17 infusions (median 4) of 5 mg/kg (range 3.8–7.3) of infliximab during a median time period of 4 months (1–17 months). Infusion reaction was noted in 13 patients (15%), with a total of 16 reactions in 450 infusions (4%). At Day 90 after the first infusion of infliximab, symptoms improved in 49% of patients, whereas 29% of patients were in remission and 13% of patients relapsed. From Day 0 to Day 90, Harvey–Bradshaw score decreased from 7.5 to 2.8 (P < 0.001), C-reactive protein from 36 to 16 mg/L (P < 0.01), and 1-hour erythrocyte sedimentation rate from 35 to 17 mm (P < 0.01). Dosage of corticosteroids decreased from to 0.59 to 0.17 mg/kg/d (P < 0.001); 53% of patients could be weaned of corticosteroids and 92% of parenteral nutrition. Treatment with infliximab is well tolerated and effective in most children and adolescents with Crohn’s disease that is refractory to conventional immunosuppressive therapy. Nevertheless, long-term efficacy remains to be shown, and further studies are urgently needed to precisely determine the best modality of continuing treatment.
Characterization of the cAMP Response Element of the Cystic Fibrosis Transmembrane Conductance Regulator Gene Promoter*

A dominant negative inhibitor of the cAMP-dependent protein kinase has been shown to inhibit the basal expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the human colon carcinoma cell line, T84. A functional cAMP response element (CRE) was localized at −48 in the CFTR promoter, and we have analyzed the interactions of this regulatory region with transcription factors. An adjacent inverted CCAAT element (Y box) at position −60 was also investigated. Mutation of the CRE or the Y box decreases the activity of the promoter in transient transfections of T84 or JEG-3 cells. Electrophoretic mobility shift assays demonstrate that CRE-binding protein (CREB) binds to the CFTR CRE with high affinity and independently of the adjacent Y box and that the CFTR CRE binds CREB and activating transcription factor-1 in nuclear extracts of T84 and CaLu-3 cells. In transient transfections of JEG-3 cells, activation of the CFTR promoter is blocked by a dominant negative CREB mutant. The CFTR CRE will also drive cAMP-mediated expression when placed upstream of a heterologous basal promoter. These results demonstrate that CFTR is a bona fide CRE-dependent gene, and we suggest that CFTR expression levels in vivo may be responsive to hormones or drugs that activate the cAMP-dependent protein kinase system.