Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome of intracerebral hemorrhage associated with different oral anticoagulants

Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH). Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]). Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.
Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: A Chinese experience

Background: Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well recognized risk factors for hepatocellular carcinoma (HCC), little is known with respect to how HBV and HCV infection affect HCC recurrence in postoperative HCC Chinese patients. The objective of this study was to determine if differences exist in preoperative characteristics and postoperative HCC recurrence in patients with different HBV and HCV infection status.
Direct calculation of the crystal–melt interfacial free energies for continuous potentials: Application to the Lennard-Jones system

Extending to continuous potentials a cleaving wall molecular dynamics simulation method recently developed for the hard-sphere system [Phys. Rev. Lett. 85, 4751 (2000)], we calculate the crystal–melt interfacial free energies, γ, for a Lennard-Jones system as functions of both crystal orientation and temperature. At the triple point, T*=0.617, the results are consistent with an earlier cleaving potential calculation by Broughton and Gilmer [J. Chem. Phys. 84, 5759 (1986)], however, the greater precision of the current calculation allows us to accurately determine the anisotropy of γ. From our data we find that, at all temperatures studied, γ111<γ110<γ100. A comparison is made to the results from our previous hard-sphere calculation and to recent results for Ni by Asta, Hoyt, and Karma [Phys. Rev. B 66 100101(R) (2002)].
MR in oncology drug development

This article reviews the use of MR in preclinical and clinical experiments to aid drug development. In particular it concentrates on the use of MR to study tumor microvasculature following treatment with anti‐vascular agents and the use of MRS to study tumor metabolism following treatment with a variety of anti‐cancer agents. The advantages and disadvantages of a variety of techniques including contrast‐ and noncontrast‐enhanced methods are discussed and the data from clinical trials using these techniques are reviewed. Despite the consensus documents produced to date for both dynamic contrast‐enhanced MRI and MRS, most of the trials reported used alternative methods, and different nomenclature for the MR parameters used. This continues to inhibit the comparison between novel therapeutics and between different trials with the same compound. Comprehensive data from multicenter trials on the reproducibility of techniques is still lacking in the literature and the implications of the available data on clinical trial design is also discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Validation of Performance Indicators for Rehabilitation of Workers With Mental Health Problems

Objective:The objective of this study was to evaluate content validity and predictive validity of 11 performance indicators for the rehabilitation of workers with mental health problems. Research Design and Subjects:Content validity was assessed by experts who evaluated the validity of the performance indicators in 2 Delphi rounds. Predictive validity was evaluated by relating the performance indicators and their sum score to the outcome of a cohort of 191 employees absent from work as a result of mental health problems. Scores for the performance indicators were obtained by processing registration forms of consultations filled out by occupational physicians. Main Outcome Measures:Three outcome measures were used: time to return to work, change in level of fatigue, and patient satisfaction. Results:Ten of the 11 performance indicators showed adequate content validity according to the expert panel. The evaluation of predictive validity yielded mixed results. One performance indicator did not show sufficient variability and was excluded from further analysis. The sum score of 9 performance indicators and performance on the evaluation of work disabilities were significantly related to a shorter time to return to work (hazard ratio [HR], respectively, 0.7; confidence interval [CI], 0.7–0.9 and 0.5; CI, 0.2–0.9). Adequate care regarding interventions aimed at providers of care in the curative sector was related to a longer time to return to work (HR, 1.8; CI, 1.1–3.0). The linear regression revealed that the sum score was not significantly related to a change in level of fatigue. However, lower quality of overall care was significantly related to moderately higher patient satisfaction (β = 0.18; P < 0.05). Conclusions:The evaluated performance indicators showed sufficient content validity and overall predictive validity, but no clear relation could be established between individual performance indicators and outcome.
Identification of glycogen synthase kinase 3α as a therapeutic target in melanoma

Deregulated expression or activity of kinases can lead to melanomas, but often the particular kinase isoform causing the effect is not well established, making identification and validation of different isoforms regulating disease development especially important. To accomplish this objective, an siRNA screen was undertaken that which identified glycogen synthase kinase 3α (GSK3α) as an important melanoma growth regulator. Melanocytes and melanoma cell lines representing various stages of melanoma tumor progression expressed both GSK3α and GSK3β, but analysis of tumors in patients with melanoma showed elevated expression of GSK3α in 72% of samples, which was not observed for GSK3β. Furthermore, 80% of tumors in patients with melanoma expressed elevated levels of catalytically active phosphorylated GSK3α (pGSK3αY279), but not phosphorylated GSK3β (pGSK3βY216). siRNA‐mediated reduction in GSK3α protein levels reduced melanoma cell survival and proliferation, sensitized cells to apoptosis‐inducing agents and decreased xenografted tumor development by up to 56%. Mechanistically, inhibiting GSK3α expression using siRNA or the pharmacological agent AR‐A014418 arrested melanoma cells in the G0/G1 phase of the cell cycle and induced apoptotic death to retard tumorigenesis. Therefore, GSK3α is a key therapeutic target in melanoma.
Regulation of GATA-3, c-maf and T-bet mRNA Expression in Bronchoalveolar Lavage Cells and Bronchial Biopsies after Segmental Allergen Challenge

Background: GATA-3 (GATA binding protein 3) and the proto-oncogene c-maf are Th2-regulating transcription factors that control the expression of interleukin (IL)-4 and IL-5, while T-bet (T-box expressed in T cells) is a Th1-specific transcription factor that controls the expression of interferon (IFN-γ). Allergen provocation in asthmatics induces a Th2-dominated cytokine profile, but so far it is unknown whether the skewed cytokine expression is reflected by the expression of the respective transcriptional regulators. Objective: The aim of this study was to determine the regulation of Th1- and Th2-specific transcription factors and cytokines in 10 atopic subjects with mild asthma and 5 nonatopic healthy controls at baseline and after segmental sham and allergen challenge. Methods: The mRNA expression of GATA-3, c-maf and T-bet was determined by real-time polymerase chain reaction in bronchoalveolar lavage (BAL) cells and bronchial biopsies. The percentage of IL-4+, IL-5+ and IFN-γ+ BAL T cells was determined by flow cytometry, and BAL levels of these cytokines were measured by ELISA. Results: In BAL cells of asthmatics, the mRNA expression of all transcription factors was increased after allergen challenge. In bronchial biopsies, the basal expression of GATA-3 was increased in asthmatics compared to healthy controls but decreased after allergen challenge. Compared to sham challenge, the percentage of IL-5+/CD4+ BAL T cells was increased after allergen challenge in asthmatics while the percentage of IFN-γ+/CD4+ and IFN-γ+/CD8+ T cells was decreased. Expression of c-maf mRNA in BAL cells correlated with IL-4+/CD4+ BAL cells and BAL IL-5 levels. Conclusions: Segmental allergen challenge in asthmatics leads to increased GATA-3, c-maf and T-bet expression in BAL cells but not in bronchial biopsies.
A dilutional immunoperoxidase study of proliferative ductal lesions and carcinomata of the breast

A dilutional immunoperoxidase study of carcinoembryonic antigen (CEA) reactivity of mild and severe epitheliosis as well as malignant ductal and lobular lesions of the breast was performed. Intraduct carcinoma with a cribriform and clinging pattern showed intracytoplasmic, glycocalyceal and intraluminal staining for CEA at higher dilutions of antiserum than cases with mild and severe epitheli‐osis. Also, many intraduct carcinomas associated with infiltration stain at a lower concentration of antiserum to CEA than pure intraduct lesions. Staining is seen at lowest concentrations in the infiltrating components. This suggests that as intraduct carcinoma becomes invasive, it loses some of its ability to store and possibly to synthesize CEA. The dilutional immunoperoxidase method could be applied routinely to cases of severe epitheliosis to differentiate them from intraduct carcinoma. However, relatively few cases were studied in this preliminary series and a further study is being carried out. The difficulties encountered using CEA as a tumour marker are outlined
Assessment and analysis of human laterality for manipulation and communication using the Rennes Laterality Questionnaire

Despite significant scientific advances, the nature of the left-hemispheric systems involved in language (speech and gesture) and manual actions is still unclear. To date, investigations of human laterality focused mainly on non-communication functions. Although gestural laterality data have been published for infants and children, relatively little is known about laterality of human gestural communication. This study investigated human laterality in depth considering non-communication manipulation actions and various gesture types involving hands, feet, face and ears. We constructed an online laterality questionnaire including 60 items related to daily activities. We collected 317 594 item responses by 5904 randomly selected participants. The highest percentages of strong left-lateralized (6.76%) and strong right-lateralized participants (75.19%) were for manipulation actions. The highest percentages of mixed left-lateralized (12.30%) and ambidextrous (50.23%) participants were found for head-related gestures. The highest percentage of mixed right-lateralized participants (55.33%) was found for auditory gestures. Every behavioural category showed a significant population-level right-side bias. More precisely, participants were predominantly right-lateralized for non-communication manual actions, for visual iconic, visual symbolic, visual deictic (with and without speech), tactile and auditory manual gestures as well as for podial and head-related gestures. Our findings support previous studies reporting that humans have left-brain predominance for gestures and complex motor activities such as tool-use. Our study shows that the Rennes Laterality Questionnaire is a useful research instrument to assess and analyse human laterality for both manipulation and communication functions.
Worldwide patterns of genomic variation and admixture in gray wolves

The gray wolf (Canis lupus) is a widely distributed top predator and ancestor of the domestic dog. To address questions about wolf relationships to each other and dogs, we assembled and analyzed a data set of 34 canine genomes. The divergence between New and Old World wolves is the earliest branching event and is followed by the divergence of Old World wolves and dogs, confirming that the dog was domesticated in the Old World. However, no single wolf population is more closely related to dogs, supporting the hypothesis that dogs were derived from an extinct wolf population. All extant wolves have a surprisingly recent common ancestry and experienced a dramatic population decline beginning at least ∼30 thousand years ago (kya). We suggest this crisis was related to the colonization of Eurasia by modern human hunter–gatherers, who competed with wolves for limited prey but also domesticated them, leading to a compensatory population expansion of dogs. We found extensive admixture between dogs and wolves, with up to 25% of Eurasian wolf genomes showing signs of dog ancestry. Dogs have influenced the recent history of wolves through admixture and vice versa, potentially enhancing adaptation. Simple scenarios of dog domestication are confounded by admixture, and studies that do not take admixture into account with specific demographic models are problematic.
How Does Collaborative Group Technology Influence Social Network Structure?

The relationship between technology and elements of the formal organization structure has long been of interest to information systems and organization researchers. A less-studied issue is how technology may also influence the informal social network structure. This research examines how various types of technological expertise relate to an individual's network centrality in the project teams of 99 MBA, MISM, and MAIS students at a large public university. To further understand this relationship, the project task was varied in terms of "uncertainty " and the formal group structures in terms of departmentation. Results indicate that individuals who are proficient with various types of technologies tend to be more central in their class advice network. However, this relationship depends on both the level of task uncertainty and group departmentation. Implications are drawn for practice and research.
Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5−/− mice

Glucose homeostasis is critically dependent on insulin release from pancreatic β-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (Vm) and the cytosolic calcium level ([Ca2+]cyt). We propose that TRPM5, a Ca2+-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca2+-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5−/− cells. Ca2+-imaging and electrophysiological analysis show that glucose-induced oscillations of Vm and [Ca2+]cyt have on average a reduced frequency in Trpm5−/− islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5−/− pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5−/− mice.
Integrin receptors play a role in the internalin B-dependent entry of Listeria monocytogenes into host cells

Listeria monocytogenes enters non-phagocytic cells by binding its surface proteins inlA (internalin) and inlB to the host’s E-cadherin and Met, respectively. The two internalins play either separate or cooperative roles in the colonization of infected tissues. Here, we studied bacterial uptake into HeLa cells using an L. monocytogenes mutant strain (ΔinlA) carrying a deletion in the gene coding for inlA. The ΔinlA mutant strain showed the capability to invade HeLa cells. The monoclonal anti-β3- and anti-β1-integrin subunit antibodies prevented bacterial uptake into the cells, while the anti-β2- and anti-β4-integrin subunit antibodies failed to affect L. monocytogenes entry into HeLa cells. Three structurally distinct disintegrins (kistrin, echistatin and flavoridin) also inhibited bacterial uptake, showing different potencies correlated to their selective affinity for the β3- and β1-integrin subunits. In addition to inducing Met phosphorylation, infection of cells by the L. monocytogenes ΔinlA mutant strain promoted the tyrosine phosphorylation of the focal adhesion-associated proteins FAK and paxillin. Our findings provide the first evidence that β3- and β1-integrin receptors play a role in the inlB-dependent internalization of L. monocytogenes into host cells.
Pharmacotherapy for male breast cancer

Breast cancer in males is uncommon, occurring at ~ 1% of the rate of female breast cancer. Male breast carcinomas tend to be highly positive for hormone receptors, including oestrogen, progesterone and androgen receptors. Owing to this, hormone therapy is recommended as the primary treatment modality. Adjuvant therapy is recommended for male breast cancers with large size or positive axillary nodes. For metastatic disease, options for therapy include tamoxifen, orchiectomy, anti-androgens with or without luteinising hormone releasing hormone analogues or combination chemotherapy. The newer hormonal treatments, such as the selective aromatase inhibitors or novel antioestrogens, have not yet been well studied in male breast cancer but have potential for efficacy in this disease.
Interaction of Kaposi's Sarcoma-Associated Herpesvirus ORF59 with oriLyt Is Dependent on Binding with K-Rta

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) displays two distinct life stages, latency and lytic reactivation. Progression through the lytic cycle and replication of the viral genome constitute an essential step toward the production of infectious virus and human disease. KSHV K-RTA has been shown to be the major transactivator required for the initiation of lytic reactivation. In the transient-cotransfection replication assay, K-Rta is the only noncore protein required for DNA synthesis. K-Rta was shown to interact with both C/EBPα binding motifs and the R response elements (RRE) within oriLyt. It is postulated that K-Rta acts in part to facilitate the recruitment of replication factors to oriLyt. In order to define the role of K-Rta in the initiation of lytic DNA synthesis, we show an interaction with ORF59, the DNA polymerase processivity factor (PF), one of the eight virally encoded proteins necessary for origin-dependent DNA replication. Using the chromatin immunoprecipitation (ChIP) assay, both K-Rta and ORF59 interact with the RRE and C/EBPα binding motifs within oriLyt in cells harboring the KSHV bacterial artificial chromosome (BAC). A transient-transfection ChIP assay demonstrated that the interaction of ORF59 with oriLyt is dependent on binding with K-Rta and that ORF59 fails to bind to oriLyt in the absence of K-Rta. Also, using the cotransfection replication assay, overexpression of the interaction domain of K-Rta with ORF59 has a dominant negative effect on oriLyt amplification, suggesting that the interaction of K-Rta with ORF59 is essential for DNA synthesis and supporting the hypothesis that K-Rta facilitates the formation of a replication complex at oriLyt.
Minocycline in active rheumatoid arthritis. A double-blind, placebo-controlled trial.

OBJECTIVE To determine the efficacy of minocycline in the treatment of rheumatoid arthritis (RA). METHODS Minocycline (maximal oral daily dose 200 mg) or placebo was administered in a 26-week, randomized, double-blind study to 80 patients with active RA, who were treated or had previously been treated with at least one disease-modifying antirheumatic drug. RESULTS There were 15 premature discontinuations: 6 (5 taking minocycline) because of adverse effects, 8 (all taking placebo) because of lack of efficacy, and 1 (taking placebo) because of intercurrent illness. There was a statistically significant improvement in the minocycline group over the placebo group. There was a pronounced improvement in laboratory parameters of disease activity; however, improvement in clinical parameters was less impressive. The observed adverse effects attributable to minocycline were mainly gastrointestinal symptoms and dizziness. CONCLUSION The results of the present study suggest that minocycline is beneficial and relatively safe in RA patients.
Antenna diversity combining schemes for WCDMA systems in fading multipath channels

In this paper, we analyze the performance of various receive antenna diversity schemes for use in combination with transmit diversity on the downlink of wideband code-division multiple-access third-generation systems. We consider open loop and closed loop versions of both maximal ratio combining and selection diversity, and study the impact of channel correlation on the performance of these schemes. We also present an analysis of the asymptotic performance of coded systems. The analytical results are compared with simulation results obtained in typical channels.
Biotherapeutic effects of probiotic bacteria on candidiasis in immunodeficient mice

Four species of probiotic bacteria were assessed for their capacities to protect athymic bg/bg-nu/nu and euthymic bg/bg-nu/+ mice from mucosal and systemic candidiasis. Each bacterial species and Candida albicans colonized the gastrointestinal tracts of both strains of mice. The presence of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, or Bifidobacterium animalis) in the gastrointestinal tracts prolonged the survival of adult and neonatal bg/bg-nu/nu mice compared to that of isogenic mice colonized with C. albicans alone. The incidence of systemic candidiasis in bg/bg-nu/nu mice was significantly reduced by each of the four probiotic bacterial species. The numbers of C. albicans present in the alimentary tracts of euthymic bg/bg-nu/+ mice were significantly reduced by L. casei GG and B. animalis. None of the probiotic bacteria species completely prevented mucosal candidiasis, but B. animalis reduced its incidence and severity. Probiotic bacteria also modulated antibody- and cell-mediated immune responses to C. albicans. The prolonged survival of mice, decreased severity of mucosal and systemic candidiasis, modulation of immune responses, decreased number of C. albicans in the alimentary tract, and reduced numbers of orogastric infections demonstrated not only that probiotic bacteria have biotherapeutic potential for prophylaxis against and therapy of this fungal disease but also that probiotic bacteria protect mice from candidiasis by a variety of immunologic (thymic and extrathymic) and nonimmunologic mechanisms in this model.