Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics of Tumors in Lymph Vessels Play an Important Role in the Tumor Progression of Invasive Ductal Carcinoma of the Breast: A Prospective Study

It is unknown whether the characteristics of tumor cells in lymph vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast. The purpose of this study was to investigate the significance of the characteristics of tumor cells in the lymph vessels in relation to the tumor progression in 393 IDC patients in comparison with well-known histological parameters. The dimensions of lymph vessel tumor emboli were measured, and their structural features, nuclear atypia, and numbers of mitotic and apoptotic figures were also assessed. Multiple regression analysis showed the dimension, the distance, the number of mitotic figures, the number of apoptotic figures, and papillary features of lymph vessel tumor emboli to be significantly associated with the increased number of cells invading the lymph vessels (P < .05). The Cox proportional hazard multivariate analyses showed that more than six apoptotic figures in lymph vessel tumor emboli significantly increased the hazard rates (HRs) of tumor recurrence and death in IDCs without nodal metastasis and that more than four mitotic figures in lymph vessel tumor emboli significantly increased the HRs of tumor recurrence and death in IDCs with nodal metastasis (P < .05). The present study showed that the histological characteristics of tumor cells in lymph vessels play a very important role in the tumor progression of IDCs.
Identification of Francisella tularensis Himar1-Based Transposon Mutants Defective for Replication in Macrophages

ABSTRACT Francisella tularensis, the etiologic agent of tularemia in humans, is a potential biological threat due to its low infectious dose and multiple routes of entry. F. tularensis replicates within several cell types, eventually causing cell death by inducing apoptosis. In this study, a modified Himar1 transposon (HimarFT) was used to mutagenize F. tularensis LVS. Approximately 7,000 Kmr clones were screened using J774A.1 macrophages for reduction in cytopathogenicity based on retention of the cell monolayer. A total of 441 candidates with significant host cell retention compared to the parent were identified following screening in a high-throughput format. Retesting at a defined multiplicity of infection followed by in vitro growth analyses resulted in identification of approximately 70 candidates representing 26 unique loci involved in macrophage replication and/or cytotoxicity. Mutants carrying insertions in seven hypothetical genes were screened in a mouse model of infection, and all strains tested appeared to be attenuated, which validated the initial in vitro results obtained with cultured macrophages. Complementation and reverse transcription-PCR experiments suggested that the expression of genes adjacent to the HimarFT insertion may be affected depending on the orientation of the constitutive groEL promoter region used to ensure transcription of the selective marker in the transposon. A hypothetical gene, FTL_0706, postulated to be important for lipopolysaccharide biosynthesis, was confirmed to be a gene involved in O-antigen expression in F. tularensis LVS and Schu S4. These and other studies demonstrate that therapeutic targets, vaccine candidates, or virulence-related genes may be discovered utilizing classical genetic approaches in Francisella.
Efficacy of Zanamivir against Avian Influenza A Viruses That Possess Genes Encoding H5N1 Internal Proteins and Are Pathogenic in Mammals

ABSTRACT In 1997, an avian H5N1 influenza virus, A/Hong Kong/156/97 (A/HK/156/97), caused six deaths in Hong Kong, and in 1999, an avian H9N2 influenza virus infected two children in Hong Kong. These viruses and a third avian virus [A/Teal/HK/W312/97 (H6N1)] have six highly related genes encoding internal proteins. Additionally, A/Chicken/HK/G9/97 (H9N2) virus has PB1 and PB2 genes that are highly related to those of A/HK/156/97 (H5N1), A/Teal/HK/W312/97 (H6N1), and A/Quail/HK/G1/97 (H9N2) viruses. Because of their similarities with the H5N1 virus, these H6N1 and H9N2 viruses may have the potential for interspecies transmission. We demonstrate that these H6N1 and H9N2 viruses are pathogenic in mice but that their pathogenicities are less than that of A/HK/156/97 (H5N1). Unadapted virus replicated in lungs, but only A/HK/156/97 (H5N1) was found in the brain. After three passages (P3) in mouse lungs, the pathogenicity of the viruses increased, with both A/Teal/HK/W312/97 (H6N1) (P3) and A/Quail/HK/G1/97 (H9N2) (P3) viruses being found in the brain. The neuraminidase inhibitor zanamivir inhibited viral replication in Madin-Darby canine kidney cells in virus yield assays (50% effective concentration, 8.5 to 14.0 μM) and inhibited viral neuraminidase activity (50% inhibitory concentration, 5 to 10 nM). Twice daily intranasal administration of zanamivir (50 and 100 mg/kg of body weight) completely protected infected mice from death. At a dose of 10 mg/kg, zanamivir completely protected mice from infection with H9N2 viruses and increased the mean survival day and the number of survivors infected with H6N1 and H5N1 viruses. Zanamivir, at all doses tested, significantly reduced the virus titers in the lungs and completely blocked the spread of virus to the brain. Thus, zanamivir is efficacious in treating avian influenza viruses that can be transmitted to mammals.
The First Phylogeographic Population Structure and Analysis of Transmission Dynamics of M. africanum West African 1— Combining Molecular Data from Benin, Nigeria and Sierra Leone

Mycobacterium africanum is an important cause of tuberculosis (TB) in West Africa. So far, two lineages called M. africanum West African 1 (MAF1) and M. africanum West African 2 (MAF2) have been defined. Although several molecular studies on MAF2 have been conducted to date, little is known about MAF1. As MAF1 is mainly present in countries around the Gulf of Guinea we aimed to estimate its prevalence in Cotonou, the biggest city in Benin. Between 2005–06 we collected strains in Cotonou/Benin and genotyped them using spoligo- and 12-loci-MIRU-VNTR-typing. Analyzing 194 isolates, we found that 31% and 6% were MAF1 and MAF2, respectively. Therefore Benin is one of the countries with the highest prevalence (37%) of M. africanum in general and MAF1 in particular. Moreover, we combined our data from Benin with publicly available genotyping information from Nigeria and Sierra Leone, and determined the phylogeographic population structure and genotypic clustering of MAF1. Within the MAF1 lineage, we identified an unexpected great genetic variability with the presence of at least 10 sub-lineages. Interestingly, 8 out of 10 of the discovered sub-lineages not only clustered genetically but also geographically. Besides showing a remarkable local restriction to certain regions in Benin and Nigeria, the sub-lineages differed dramatically in their capacity to transmit within the human host population. While identifying Benin as one of the countries with the highest overall prevalence of M. africanum, this study also contains the first detailed description of the transmission dynamics and phylogenetic composition of the MAF1 lineage.
Overparenting and Homework: The Student's Task, But Everyone's Responsibility

A high level of parental involvement is widely considered to be essential for optimal child and adolescent development and wellbeing, including academic success. However, recent consideration has been given to the idea that extremely high levels of parental involvement (often called ‘overparenting’ or ‘helicopter parenting’) might not be beneficial. This study used a newly created overparenting measure, the Locke Parenting Scale (LPS), to investigate the association of overparenting and children's homework. Eight hundred and sixty-six parents completed online questionnaires about their parenting beliefs and intentions, and their attitudes associated with their child's homework. Parents with higher LPS scores tended to take more personal responsibility for the completion of their child's homework than did other parents, and ascribed greater responsibility for homework completion to their child's teacher. However, increased perceived responsibility by parents and teachers was not accompanied by a commensurate reduction in what they perceived was the child's responsibility. Future research should examine whether extreme parental attitudes and reported behaviours translate to validated changes in actual homework support.
Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Although previous studies have emphasized the vulnerability of the default mode network (DMN) in Alzheimer’s disease (AD), little is known about the involvement of other functional networks and their relationship to clinical phenotype. To test whether clinicoanatomic heterogeneity in AD is driven by the involvement of specific networks, network connectivity was assessed in healthy subjects by seeding regions commonly and specifically atrophied in three clinical AD variants: early-onset AD (age at onset, <65 y; memory and executive deficits), logopenic variant primary progressive aphasia (language deficits), and posterior cortical atrophy (visuospatial deficits). Four-millimeter seed regions of interest were used to obtain intrinsic connectivity maps in 131 healthy controls (age, 65.5 ± 3.5 y). Atrophy patterns in independent cohorts of AD variant patients and their correspondence to connectivity networks in controls were also assessed. The connectivity maps of commonly atrophied regions of interest support posterior DMN and precuneus network involvement across AD variants, whereas seeding regions specifically atrophied in each AD variant revealed distinct, syndrome-specific connectivity patterns. Goodness-of-fit analysis of each connectivity map with network templates showed the highest correspondence between the early-onset AD seed connectivity map and anterior salience and right executive-control networks, the logopenic aphasia seed connectivity map and the language network, and the posterior cortical atrophy seed connectivity map and the higher visual network. Connectivity maps derived from controls matched regions commonly and specifically atrophied in the patients. Our findings indicate that the posterior DMN and precuneus network are commonly affected in AD variants, whereas syndrome-specific neurodegenerative patterns are driven by the involvement of specific networks outside the DMN.
Characteristics of the U.S. EPA's Office of Pesticide Programs' toxicity information databases.

The United States Environmental Protection Agency's Office of Pesticide Programs (OPP) requires that data from toxicity testing be submitted to the OPP to support the registration of pesticide chemicals. Once the toxicity data are submitted, they are entered into various toxicity databases. The studies are listed in an archival database to catalog and allow retrieval of the study for review. Reviews of toxicity studies are then placed into a separate database that can be retrieved to support a regulatory position. Toxicity information for health effects other than cancer and gene mutations from chronic exposure is reviewed through a reference dose (RfD) approach, and these decisions and supporting data are entered into an RfD database. Carcinogenicity data are reviewed by a peer review process, and these decisions are entered into a newly developed database to show the regulatory decision with supporting data. The mutagenicity data are reviewed and acceptable data are entered into the Genetic Activity Profile system to catalog and display the submitted information. These databases contain the information used for hazard evaluations as part of the OPP review of pesticide chemicals.
SiGe broadband amplifiers with up to 80 GHz bandwidth for optical applications at 43 Gbit/s and beyond

Two broadband amplifiers for 43 Gbit/s data transmission were realized in a SiGe-HBT technology with ft = 120 GHz and fmax = 100 GHz: a differential lumped limiting amplifier with 36 dB differential gain and 26 GHz bandwidth and a two stage distributed amplifier with a gain-bandwidth product of 820 GHz. Additionally, for applications beyond 43 Gbit/s, a distributed amplifier was realized in a more advanced SiGe process (ft, fmax > 200 GHz). This amplifier achieves 13 dB gain and more than 80 GHz bandwidth, which is the highest bandwidth reported so far for Si-based amplifiers.
Exact solution of a Yang-Baxter spin-1/2 chain model and quantum entanglement

Entanglement is believed to be crucial in macroscopic physical systems for understanding the collective quantum phenomena such as quantum phase transitions. We start from and solve exactly a Yang-Baxter spin-$1∕2$ chain model with inhomogeneous and anisotropic short-range interactions. For the ground state, we show the behavior of neighboring entanglement in the parameter space and find that the inhomogeneous coupling strengths affect entanglement in a distinctive way from the homogeneous case, but this would not affect the coincidence between entanglement and quantum criticality.
Towards Cost-based Optimization for Data-intensive Web Service Computations

The recent popularity of XML and Web services has lead to a surge in models and platforms for distributed XML data management applications. This work investigates performance issues involved in the deployment of the ActiveXML (AXML) platform for such applications. AXML documents are XML documents, part of which is extensional (present in the document), while part is intensional (specified as calls to Web services). Materializing an AXML document thus requires activating all service calls, and gathering the call results in the document.
Comparing Mortality Rates on Capd/Ccpd and Hemodialysis the Canadian Experience: Fact or Fiction?

← Objective To compare mortality rates on hemodialysis (HD) to rates on continuous ambulatory/cyclic peritoneal dialysis (CAPD/CCPD), to contrast our results with those of other recent investigations, and to discuss reasons for discrepancies. ← Data Sources Patient -specific data obtained from the Canadian Organ Replacement Register on patients initiating renal replacement therapy (RRT) between 1 January 1990 and 31 December 1995 (n = 14483). Recent mortality comparisons of CAPD and HD. ← Main Outcome Measures Mortality rate ratio (RR) based on “as-treated” (AT) analysis incorporating treatment modality switches and adjusting for age, primary renal diagnosis, and comorbid conditions using Poisson regression. Hazard ratios (HR) were estimated using Cox regression and based on an “intent-to-treat” (ITT) analysis wherein patients were classified based on dialytic modality received on follow-up day 90. ← Results Adjusted mortality rates were significantly decreased on CAPD/CCPD relative to HD [RR = 0.73, 95% confidence interval (CI) = (0.69, 0.77)] based on the AT analysis. Most of the protective effect of CAPD/CCPD was concentrated in the first 2 years of follow-up post-RRT initiation. Based on the ITT analysis, the estimated CAPD/ CCPD effect was greatly reduced, with HR = 0.93 (0.87, 0.99). ← Conclusions We provide further evidence that CAPD/ CCPD is not an inferior dialytic modality to HD, particularly in the short term. Comparing mortality rates on CAPD/ CCPD and HD is inherently difficult due to the potential for bias. Discrepancies between our results and those of previous investigations, and variability in findings among previous studies, relate to differences in clinical and demographic setting, patient populations, study design, statistical methods, and interaction between the dialytic modality effect and various other covariables.
Dynamic Optimization of a Batch Pharmaceutical Reaction using the Design of Dynamic Experiments (DoDE): the Case of an Asymmetric Catalytic Hydrogenation Reaction

Abstract The present research work aims to demonstrate the effectiveness of the new methodology of Design of Dynamic Experiments (DoDE) in optimizing an important pharmaceutical reaction. An easily developed response surface model (RSM) is used instead of a hard to develop knowledge-driven process model. The DoDE approach allows the experimenter to introduce dynamic factors in the design, which during the RSM optimization are treated as all the other factors, simplifying the analysis significantly, leading to the rapid optimization of batch processes with respect to time-varying decision variables. The DoDE approach enables the discovery of optimal time-variant operating conditions that are better than the optimal time-invariant conditions discovered by the classical Design of Experiments (DoE) approach. In the present case of the asymmetric catalytic hydrogenation, 24 experiments are conducted for the DoDE approach and the best run results in a 45% improvement comparing to the best run of 17 runs of the DoE approach. This is achieved by applying a decreasing temperature profile during the batch reaction. Optimization of the economic performance index of the process through the respective response surface models defines an optimum operation. The DoDE optimum operation is better than the respective one through the DoE. The DoDE advantage increases as the required quality level for the final product is higher. For the medium quality, the DoDE approach results in an improvement of 30% over the DoE one.
Maintenance Therapy with Immunomodulatory Drugs after Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials

Background Although high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) has been confirmed to result in longer remission time than conventional chemotherapy, multiple myeloma (MM) remains incurable. Post-ASCT maintenance is considered as a strategy for obtaining durable remissions and preventing tumor progression. Randomized controlled trials (RCTs) studying maintenance therapy with immunomodulatory drugs (IMiDs) after ASCT have shown some valuable survival improvements. This meta-analysis of RCTs therefore assesses the effect of post-ASCT IMiDs maintenance on MM patients. Methods We performed a meta-analysis to evaluate the impact of IMiDs (thalidomide or lenalidomide) as post-ASCT maintenance therapy on the survival of newly diagnosed MM patients. The outcomes for this meta-analysis were progression-free survival (PFS) and overall survival (OS). Results Eight RCTs enrolling 3514 patients were included for analysis. An obvious improvement in Os (hazard ratio [HR] 0.75) and a significant PFS advantage (HR 0.58) with post-ASCT IMiDs maintenance was revealed. Thalidomide maintenance after ASCT can result in significant benefit in Os (HR 0.72), particularly combined with corticosteroids (HR 0.66). Conclusions MM patients after ASCT have a significant overall survival benefit with IMiDs maintenance. IMiDs maintenance was justified for MM patients who received HDT with ASCT.
Baseline HbA1c predicts attainment of 7.0% HbA1c target with structured titration of insulin glargine in type 2 diabetes: a patient‐level analysis of 12 studies

To determine whether baseline characteristics, especially haemoglobin A1c (HbA1c), predict the likelihood of reaching HbA1c ≤ 7.0% or the risk of experiencing hypoglycaemia after the addition of insulin glargine to oral therapy in type 2 diabetes.
ATP- and Gap Junction–dependent Intercellular Calcium Signaling in Osteoblastic Cells

Many cells coordinate their activities by transmitting rises in intracellular calcium from cell to cell. In nonexcitable cells, there are currently two models for intercellular calcium wave propagation, both of which involve release of inositol trisphosphate (IP3)- sensitive intracellular calcium stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein connexin43 (Cx43), are well dye coupled, and lack P2U receptors, transmitted slow gap junction-dependent calcium waves that did not require release of intracellular calcium stores. UMR 106-01 cells predominantly express the gap junction protein connexin 45 (Cx45), are poorly dye coupled, and express P2U receptors; they propagated fast calcium waves that required release of intracellular calcium stores and activation of P2U purinergic receptors, but not gap junctional communication. ROS/P2U transfectants and UMR/Cx43 transfectants expressed both types of calcium waves. Gap junction–independent, ATP-dependent intercellular calcium waves were also seen in hamster tracheal epithelia cells. These studies demonstrate that activation of P2U purinergic receptors can propagate intercellular calcium, and describe a novel Cx43-dependent mechanism for calcium wave propagation that does not require release of intracellular calcium stores by IP3. These studies suggest that gap junction communication mediated by either Cx43 or Cx45 does not allow passage of IP3 well enough to elicit release of intracellular calcium stores in neighboring cells.
Report from the first international workshop on computer vision meets databases (CVDB 2004)

This report summarizes the presentations and discussions of the First International Workshop on Computer Vision meets Databases, or CVDB 2004, which was held in Paris, France, on June 13, 2004. The workshop was co-located with the 2004 ACM SIGMOD/PODS conferences and was attended by forty-two participants from all over the world.
An increase in epicardial adipose tissue is strongly associated with carotid intima-media thickness and atherosclerotic plaque, but LDL only with the plaque

Objective: Carotid intima-media thickness (CIMT) is reliable marker of subclinical atherosclerosis and cardiovascular events. Until today, there was no study that investigated whether epicardial adipose tissue (EAT), which is a surrogate for lipid depot in a special visceral tissue or circulating lipids, is more important for CIMT and atherosclerotic plaque. Methods: Our study, having cross-sectional and prospective observational design, included 252 patients who were admitted to our outpatient clinic. EAT identified as an echo-free space under the pericardial layer on 2-dimensional echocardiography, was measured perpendicularly in front of the right ventricular free wall at end-systole. Results: EAT significantly correlated with CIMT (r=0.623, p<0.001). CIMT was significantly increased with rising EAT thickness (0.72±0.15 mm, 0.85±0.16 mm, and 0.95±0.12 mm in patients with EAT <5 mm, 5–7, and >7 mm, p<0.001, respectively). Multiple linear regression analysis revealed that age (Beta: 0.406, p<0.001), male gender (Beta: 0.244, p<0.001), and EAT (Beta: 0.450, p<0.001) as independent correlates of CIMT. Otherwise, in logistic regression analysis, only EAT (OR, 1.386; 95% CI, 1.203–1.597, p<0.001) and LDL cholesterol (OR, 1.013; 95% CI, 1.002–1.013, p=0.02) were independent predictors for presence of carotid plaque. Conclusion: Our study showed that EAT has a relationship with both CIMT and the presence of carotid plaque, but LDL is independently related to the plaque. This finding suggests that EAT thickness may be a risk factor and biomarker, playing an important role beginning from early stages of atherosclerosis, unlike LDL cholesterol, which appear to have a role in later stages of atherosclerosis.