Miracle-dz/UniFAR-FTUs huggingface dataset:
Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway

Summary Sulforaphane, a dietary isothiocyanate found in cruciferous vegetables, has been shown to exert beneficial effects in animal models of cardiovascular diseases. However, its effect on platelet aggregation, which is a critical factor in arterial thrombosis, is still unclear. In the present study, we show that sulforaphane inhibited human platelet aggregation caused by different receptor agonists, including collagen, U46619 (a thromboxane A2 mimic), protease-activated receptor 1 agonist peptide (PAR1-AP), and an ADP P2Y12 receptor agonist. Moreover, sulforaphane significantly reduced thrombus formation on a collagen-coated surface under whole blood flow conditions. In exploring the underlying mechanism, we found that sulforaphane specifically prevented phosphatidylinositol 3-kinase (PI3K)/Akt signalling, without markedly affecting other signlaling pathways involved in platelet aggregation, such as protein kinase C activation, calcium mobilisation, and protein tyrosine phosphorylation. Although sulforaphane did not directly inhibit the catalytic activity of PI3K, it caused ubiquitination of the regulatory p85 subunit of PI3K, and prevented PI3K translocation to membranes. In addition, sulforaphane caused ubiquitination and degradation of phosphoinositide-dependent kinase 1 (PDK1), which is required for Akt activation. Therefore, sulforaphane is able to inhibit the PI3K/Akt pathway at two distinct sites. In conclusion, we have demonstrated that sulforaphane prevented platelet aggregation and reduced thrombus formation in flow conditions; our data also support that the inhibition of the PI3K/Akt pathway by sulforaphane contributes it antiplatelet effects.
Nocardia farcinica as a Pathogen of Lung Infection

Strains of Nocardia asteroides and the type strain of Nocardia farcinica, ATCC 3318, have been considered to be homogeneous (7, 8), and Gordon and Mihm (8) proposed N. asteroides as the type species of the genus Nocardia, assigning strain ATCC 3318 to the species N. asteroides. In contrast, Mariat (13) and Cerbon (3) suggested the heterogeneity of N. asteroides. Magnusson and Mariat (12) differentiated strains received as N. farcinica from strains of N. asteroides by skin reactions in guinea pigs. Tsukamura (18) stated that strains received as N. asteroides could be divided into two distinct clusters by numerical classification, and designated the group containing the ATCC 3318 strain as N.
An embolus in the right atrium caught in the Chiari network and resistant to thrombolysis

This case report describes a patient with thromboemboli trapped in the Chiari network within the right side of the heart and resistant to thrombolysis. The right atrial masses were completely removed under cardiopulmonary bypass. Histological evaluation confirmed a mixed thromboemboli, with thrombus structures showing signs of organisation and surrounded by a fibrous capsule. The plasma level of the plasminogen activator inhibitor type-1 (PAI-1) was 50% higher than the normal upper limit. In this presented case, the Chiari network displayed a protective function but the expansion and organisation of the thromboembolus found there made it resistant to lytic treatment. Another important factor that could have influenced the resistance to thrombolysis was the high level of PAI-1.
A cross-cultural analysis of customer perception towards hotel service quality and behavioral intention

the purpose of this study was to examine how cultural dimension related to service quality and behavioral intention in tourist hotel industry. To investigate this issue, 761 tourists visiting Beijing were interviewed. These tourists included 195 Chinese, 189 Korean, 192 Japanese and 185 American. Results from this study suggested that there were cross-cultural differences toward service quality dimensions and the relationships between service quality and behavioral intention dimensions. Results also showed that cultural dimensions are related to service quality dimensions. This study may enhance both efficiency and effectiveness in international hotel management. Managerial implications of this study could be used to allocate managerial resources and develop international marketing strategies for dealing with culturally diverse customers in hotel industry.
Posttreatment and physiologic occlusal changes comparison.

OBJECTIVE To compare posttreatment and postretention occlusal changes with the physiologic occlusal changes caused by natural development of untreated subjects. MATERIALS AND METHODS The sample was divided into three groups. Group 1 comprised 97 subjects treated with four premolar extractions at a mean pretreatment (T0) age of 13.03 years, a mean posttreatment (T1, first observation) age of 15.12 years, and a mean postretention (T2, second observation) age of 20.52 years. The mean observation period (T2-T1) was 5.39 years. Group 2 comprised 58 subjects treated nonextraction at a mean pretreatment age of 12.83 years, a mean posttreatment age of 14.99 years, a mean postretention age of 20.22 years, and a mean observation period of 5.22 years. Group 3 comprised 114 untreated subjects at a mean age at T1 of 14.91 years and at T2 of 20.48 years. The mean observation period was 5.56 years. Dental casts were evaluated using the Peer Assessment Rating (PAR) index and the Little irregularity index in maxillary and mandibular arches. Changes in PAR and Little indexes were compared among the three groups by analysis of variance and Tukey tests. RESULTS Intergroup comparison showed that at T1 and T2 the treated groups presented smaller PAR and Little indexes than the untreated group. In the observation period, the treated groups showed greater increase in PAR and Little maxillary indexes than the untreated group. The extraction group showed a greater increase of the Little mandibular index than the untreated group. CONCLUSIONS The treated groups showed more changes according to PAR and Little maxillary indexes than the untreated group. The posttreatment change of the mandibular anterior crowding of the treated extraction group was greater than the mandibular crowding caused by physiologic changes in the untreated group.
Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons.

OBJECTIVE To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents. METHODS Randomized controlled trials in RA patients, investigating the effects of drug treatment on the percentage of the annual radiographic progression rate (PARPR) were included in a meta-analysis performed with the use of Review Manager 5.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. RESULTS Data from 70 trials (112 comparisons, 16 interventions) were summarized in 21 meta-analyses. Compared with placebo, the PARPR was 0.65% smaller in the single-DMARD group (P < 0.002) and 0.54% smaller in the glucocorticoid group (P < 0.00001). Compared with single-DMARD treatment, the PARPR was 0.62% smaller in the combination-DMARD group (P < 0.001) and 0.61% smaller in the biologic agent plus methotrexate (MTX) group (P < 0.00001). The effect of a combination of 2 DMARDs plus step-down glucocorticoids did not differ from the effect of a biologic agent plus MTX (percentage mean difference -0.07% [95% confidence interval -0.25, 0.11]) (P = 0.44). CONCLUSION Treatment with DMARDs, glucocorticoids, biologic agents, and combination agents significantly reduced radiographic progression at 1 year, with a relative effect of 48-84%. A direct comparison between the combination of a biologic agent plus MTX and the combination of 2 DMARDs plus initial glucocorticoids revealed no difference. Consequently, biologic agents should still be reserved for patients whose RA is resistant to DMARD therapy. Future trials of the effects of biologic agents on RA should compare such agents with combination treatments involving DMARDs and glucocorticoids.
Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays

Acute respiratory tract infection is a leading cause of hospital admission of children. This study used a broad capture, rapid and sensitive method (multiplex PCR assay) to detect 20 different respiratory pathogens including influenza A subtypes H1, H3, and H5; influenza B; parainfluenza types 1, 2, 3, and 4; respiratory syncytial virus (RSV) groups A and B; adenoviruses; human rhinoviruses; enteroviruses; human metapneumoviruses; human coronaviruses OC43, 229E, and SARS‐CoV; Chlamydophila pneumoniae; Legionella pneumophila; and Mycoplasma pneumoniae; from respiratory specimens of 475 children hospitalized over a 12‐month period for acute respiratory tract infections. The overall positive rate (47%) was about twice higher than previous reports based on conventional methods. Influenza A, parainfluenza and RSV accounted for 51%, and non‐cultivable viruses accounted for 30% of positive cases. Influenza A peaked at March and June. Influenza B was detected in January, February, and April. Parainfluenza was prevalent throughout the year except from April to June. Most RSV infections were found between February and September. Adenovirus had multiple peaks, whereas rhinovirus and coronavirus OC43 were detected mainly in winter and early spring. RSV infection was associated with bronchiolitis, and parainfluenza was associated with croup; otherwise the clinical manifestations were largely nonspecific. In general, children infected with influenza A, adenovirus and mixed viruses had higher temperatures. In view of the increasing concern about unexpected outbreaks of severe viral infections, a rapid multiplex PCR assay is a valuable tool to enhance the management of hospitalized patients, and for the surveillance for viral infections circulating in the community. J. Med. Virol. 81:153–159, 2009. © 2008 Wiley‐Liss, Inc.
Is Ileoscopy With Biopsy Worthwhile in Patients Presenting With Symptoms of Inflammatory Bowel Disease?

Objective:To assess the value of adding ileoscopy with biopsy to colonoscopy, hence increasing the indications for ileoscopy in patients presenting with symptoms of inflammatory bowel disease.Methods:Two hundred fifty-seven patients with persistent diarrhea and 43 patients with sporadic colonic polyps were studied prospectively. The final diagnosis based on clinical and follow-up data, the histology of multiple ileal biopsies, and endoscopic findings were analyzed.Results:Endoscopic lesions of the terminal ileum were found in 123 of 300 patients. In the 43 patients with colonic polyps, no ileal lesions were seen. Ileal disease without colonic involvement was present in 44 of 123 patients. Microscopic lesions of the ileum were present in 125 of 300, or in 125 of 257 (49%) with symptoms of diarrhea. Two of these had a normal endoscopy. Thirteen patients had a diffuse colitis and 11 had a predominantly left-sided colitis, both originally suggestive of ulcerative colitis. Crohn's disease was diagnosed in 88 patients and infectious disease in 17. Ileal biopsies were essential for the diagnosis in 15 patients and were contributive in 53. Granulomas, solitary giant cells, pseudopyloric gland metaplasia, eosinophils, and a disturbed villous architecture were the most important lesions observed in Crohn's disease and were contributive for this diagnosis.Conclusions:Ileoscopy with biopsy is useful in carefully selected patients presenting with symptoms of inflammatory bowel disease. The main indications are diagnosis of isolated ileal disease in the presence of a normal colon and differential diagnosis in patients with pancolitis and predominantly left-sided colitis. Multiple biopsy specimens show definite pathology in almost half of the patients.
Melatonin, circadian rhythms, and sleep.

Disturbances in circadian rhythms often result in disturbances in sleep. Examples include syndromes in which sleep time is delayed or advanced, the sleeping problems associated with jet lag and shift work, and the sleep disorders that occur in totally blind persons with free-running circadian rhythms (i.e., rhythms that are not synchronized to the 24-hour day). 1 The hormone melatonin can be used both to characterize and to treat such disorders. The circadian rhythm of melatonin secretion is generated by the central pacemaker, or “clock,” in the suprachiasmatic nuclei of the hypothalamus, and like many other circadian rhythms, it is synchronized to .
A Case Report of Homocystinuria With Dystonia and Stroke

Inherited homocystinuria is a rare autosomal recessive aminoacidopathy which through early diagnosis can prevent its severe neurologic and vascular complications. Here we report a 9-year-old girl with homocystinuria, presenting with sequential symptoms of bilateral lens dislocation, skeletal complication, and eventually dystonia from the age of 4 years. Laboratory evaluation revealed severe high serum homocysteine level. Although pathophysiologically unexplained, evidence of deep white matter watershed infarct along with remarkable ipsilateral carotid stenosis was detected on the contralateral side of the dystonia in the neuroimaging. Treatment with high dose of pyridoxine relieved limb and gait dystonia significantly, while carotid stenosis remained unchanged. Therefore, homocysteine might have both structural and irreversible effect and functional and reversible impact that could be overcome even in late stages.
Condition on composite numbers easily factored with elliptic curve method

For a composite integer N that we would like to factor, we consider a condition for the elliptic curve method (ECM) using N as a scalar value to succeed and show that if N has a prime factor p such that p = (DV +1)/4, V ∈ Z, D ∈ {3, 11, 19, 35, 43, 51, 67, 91, 115, 123, 163, 187, 235, 267, 403, 427}, we can find a non-trivial divisor of N (multiple of p) in a short time. Although, Cheng already provided the same result for D ∈ {3, 11, 19, 43, 67, 163} [2], this paper uses another approach. In other words, to factor N , Cheng’s work uses the ECM using the N -th division polynomial and this paper uses the ECM using arithmetic on a residue ring of ZN [X]. In the authors’ implementation on PARI/GP, a 1024-bit N was factored in a few seconds when p was 512 bits.
When Lithium Hurts: A Look at Ebstein Anomaly

Ebstein anomaly (EA) is a congenital defect of the tricuspid valve (TV) and the right ventricle (RV) in which the attachments of the septal and posterior valve leaflets are apically displaced. The latter creates 3 morphologic components inside the right heart, namely the right atrium proper, the atrialized RV, and the functional RV. This rare anomaly accounts for <1.5% of all congenital heart diseases. The current opinion among authors is that it is a genetically heterogeneous condition caused by failure of delamination of the TV leaflets from the underlying myocardium and the interventricular septum. Its characteristic electrocardiographic findings include tall, broad, right atrial P waves, prolonged PR intervals, and deep Q waves in the right precordial leads. Echocardiography is currently the best technique for diagnosing this anomaly, although cardiac magnetic resonance imaging is also gaining traction as an alternative modality. The management strategies for EA correlate with the age of the patient, severity of the heart disease, and/or associated cardiac abnormalities. TV repair, rather than valve replacement, is preferred because of its favorable long-term prognosis. Nevertheless, a large, randomized study is still needed to compare the different valve repair techniques used in patients with EA.
Airway gene transfer using cationic emulsion as a mucosal gene carrier

Delivery of genes to airway mucosa would be a very valuable method for gene therapy and vaccination. However, there have been few reports on suitable gene delivery systems for administration. In this study, we use a cationic emulsion system, which is physically stable and facilitates the transfer of genes in the presence of up to 90% serum, as a mucosal gene carrier.
Classification of malignant and benign liver tumors using a radiomics approach

Correct diagnosis of the liver tumor phenotype is crucial for treatment planning, especially the distinction between malignant and benign lesions. Clinical practice includes manual scoring of the tumors on Magnetic Resonance (MR) images by a radiologist. As this is challenging and subjective, it is often followed by a biopsy. In this study, we propose a radiomics approach as an objective and non-invasive alternative for distinguishing between malignant and benign phenotypes. T2-weighted (T2w) MR sequences of 119 patients from multiple centers were collected. We developed an efficient semi-automatic segmentation method, which was used by a radiologist to delineate the tumors. Within these regions, features quantifying tumor shape, intensity, texture, heterogeneity and orientation were extracted. Patient characteristics and semantic features were added for a total of 424 features. Classification was performed using Support Vector Machines (SVMs). The performance was evaluated using internal random-split cross-validation. On the training set within each iteration, feature selection and hyperparameter optimization were performed. To this end, another cross validation was performed by splitting the training sets in training and validation parts. The optimal settings were evaluated on the independent test sets. Manual scoring by a radiologist was also performed. The radiomics approach resulted in 95% confidence intervals of the AUC of [0.75, 0.92], specificity [0.76, 0.96] and sensitivity [0.52, 0.82]. These approach the performance of the radiologist, which were an AUC of 0.93, specificity 0.70 and sensitivity 0.93. Hence, radiomics has the potential to predict the liver tumor benignity in an objective and non-invasive manner.
Discontinuation of Tenofovir Disoproxil Fumarate for Presumed Renal Adverse Events in Treatment-Naïve HIV-1 Patients: Meta-analysis of Randomized Clinical Studies

Abstract Background: Safety and efficacy of tenofovir disoproxil fumarate (TDF) as a component of antiretroviral therapy (ART) have been demonstrated in clinical trials. TDF nephrotoxicity has been reported in both HIV-infected and noninfected patients. This meta-analysis explored the frequency of discontinuation attributed to renal adverse events (AEs) in randomized, controlled clinical studies that used TDF-containing regimens for ART-naïve, HIV-infected patients. Methods: A literature search of 4 electronic databases through October 31, 2013 was utilized. RCTs included were limited to randomized, prospective, comparative design in ART treatment-naïve adults with HIV-1 infections receiving ART. Studies included trials containing TDF treatment regimens, with or without a non-TDF control group. Study design, follow-up, size of study population, treatment group, patient demographics, number of patients exposed to TDF or non-TDF control, baseline characteristics, investigator-defined criteria for renal AEs, and number of discontinuations due to a presumed renal AEs were extracted. Results: Twenty-one clinical studies met the selection criteria. Treatment duration ranged from 48 to 288 weeks. Renal AEs led to study drug discontinuation in 44 of 10,129 patients exposed to TDF (0.43%; 95% CI, 0.32%-0.58%) and 2 of 2,013 patients exposed to non-TDF-containing regimens (0.10%; 95% CI, 0.01%-0.36%). In 5 randomized, controlled studies that included a non-TDF comparator, the estimated risk difference between the treatment groups (TDF vs non-TDF) was 0.50% (95% CI, 0.13%-0.86%; P = .007). Conclusions: In clinical studies using TDF-containing regimens, the rate of discontinuations due to renal AEs was low, but was slightly higher than in studies using non-TDF comparators.
The p21Cip1 protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers

Liver cells from p21Cip1−/− mice subjected to partial hepatectomy (PH) progress into DNA synthesis faster than those from wild‐type mice. These cells also show a premature induction of cyclin E/cyclin‐dependent kinase (CDK) 2 activity. We studied the mechanisms whereby cells lacking p21Cip1 showed a premature induction of this activity. Whereas the levels of CDK2, cyclin E, and p27Kip1 were similar in both wild‐type and p21Cip1−/− mice, those of the activator CDC25A were much higher in p21Cip1−/− quiescent and regenerating livers than in wild‐type animals. Moreover, p21Cip1−/− cells also showed a premature translocation of CDC25A from cytoplasm into the nucleus. The ectopic expression of p21Cip1 into mice embryo fibroblasts from p21Cip1−/− mice decreased the levels of CDC25A and delayed its nuclear translocation. The levels of CDC25A messenger RNA in p21Cip1−/− cells were higher than in wild‐type cells, suggesting that this increase might be responsible, at least in part, for the high levels of CDC25A protein in these cells. Thus, the results reported here indicate that p21Cip1 regulates the levels and the intracellular localization of CDC25A. We also found a good correlation between CDC25A nuclear translocation and cyclin E/CDK2 activation. In conclusion, premature translocation of CDC25A to the nucleus might be involved in the advanced induction of cyclin E/CDK2 activity and DNA replication in cells from animals lacking p21Cip1.
Vitamin Profiles in Elderly Persons Living at Home or in Nursing Homes, versus Profile in Healthy Young Subjects

ABSTRACT: The vitamin profile of 473 elderly persons was compared with that of 204 healthy volunteers (controls). Of the 473 elderly, 327 (mean age 87) lived in nursing homes, and 146 (mean age 77) lived at home. The 204 controls were in the 20–50 year age group. The circulating levels of biotin, pantothenate, riboflavin, vitamins A, B6, B12, C, E, folate, thiamine, nicotinate, and carotenes were determined in all groups. Hypovitaminemia was not obvious for biotin, pantothenate, riboflavin, vitamins A, E, and carotenes in either the institutional or non‐institutional elderly. Thiamine, vitamin C and vitamin B12 levels were strikingly depressed in the non‐institutional elderly as compared with the institutional population or the controls. Over 30 percent of the institutional elderly had vitamin B6 and nicotinate hypovitaminemia compared to the controls. Both the institutional and the non‐institutional elderly showed depressed levels of folate and vitamin B12. Vitamin supplementation reduced the percentage of folate and B12 deficits. The marked vitamin deficits in the institutional population, in descending order of incidence were: vitamin B6, nicotinate, vitamin B12, folate, thiamine, and ascorbate, whereas the pattern for the non‐institutional elderly was: vitamin B12, thiamine, ascorbate, vitamin B6, nicotinate, and folate. In the 473 elderly studied, vitamin B6, nicotinate, and vitamin B12, in that order, were the most common deficits; folate, thiamine and ascorbate deficits comprised a lesser percentage. The role of vitamin deficits and the effects upon the aging population are discussed.