Miracle-dz/UniFAR-FTUs huggingface dataset:
Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

INTRODUCTION Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. PURPOSE To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). METHODS An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. RESULTS The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. CONCLUSIONS EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.
A new soft switching coupled inductor half bridge current fed converter

In this paper a new zero voltage switching current-fed half bridge converter with an active clamp circuit is proposed. The active clamp circuit not only absorbs the voltage surge across switches at turn off instance due to leakage inductance, but also provides soft switching condition for all the semiconductor elements. Implementation of control circuit is very simple since the converter is PWM controlled and the auxiliary switches turn on are complementary with respect to main switches. In the proposed converter, two coupled inductor are applied in conventional half bridge current fed converter for increasing converter gain. The simulation results are presented to verify the converter operation.
Assessing the Impact of a Sacral Resection on Morbidity and Survival After Extended Radical Surgery for Locally Recurrent Rectal Cancer

Objectives: To describe the experience of sacrectomy with extended radical resection in the treatment of locally recurrent rectal cancer. Background: Resections of the bony pelvis, especially the sacrum, are becoming more common as part of extended radical exenterations for patients with recurrent rectal cancer. However, sacrectomy has been shown to carry a significant decrease in survival. Morbidity rates have been associated with the level of the sacrectomy (ie, >S3 junction). Methods: An analysis was conducted using prospective data from patients with recurrent rectal cancer who underwent pelvic exenteration involving sacrectomy from July 1998 until June 2011. The impact of the proximal level of sacrectomy [low (⩽S3) vs high (≥S2–S3 disc)] was compared. Results: Of 240 exenteration patients, 79 underwent sacrectomy, with 49 for recurrent rectal cancer. An R0 margin was achieved in 36 (74%) patients. Achievement of clear operative margins (R0) conferred a large and significant benefit for disease-free survival compared with R1 and R2 resections (median 45 months vs 19 and 8 months, respectively; P = 0.045). Complications were reported in 40 (82%) patients, with major and minor complications in 19 (39%) and 38 (78%) patients, respectively. The proximal level of the sacrectomy (high vs low) did not significantly impair the ability to achieve a clear margin and was not associated with an increase in major or minor complications. Conclusions: This large, single-center series has demonstrated that extended pelvic exenteration involving sacrectomy has excellent R0 margins and survival rates for recurrent rectal cancer. A high sacrectomy has comparable results with a more distal abdominosacral resection.
Cognitive decline in Parkinson’s disease: A prospective longitudinal study

Abstract This controlled prospective study examined the evolution and predictors of cognitive decline in Parkinson’s disease (PD). Consecutive patients diagnosed at baseline with PD (n = 89), established PD (EPD) patients (n = 52) with a mean disease duration of 6.5 years, and healthy control subjects (n = 64) underwent extensive neuropsychological assessment twice, approximately 3 years apart. A standardized regression-based method, normative data, and multivariate normative comparisons were used to assess the cognitive course of PD. Cognitive performance of newly diagnosed patients decreased significantly over time, particularly on measures of psychomotor speed and attention and to a lesser extent on tests of memory, visuospatial skills, and executive functions. About 50% of the patients showed cognitive decline and 9% developed dementia. Similar results were observed in EPD patients. None of the baseline features predicted cognitive change in newly diagnosed patients, whereas age at disease onset and axial impairment (postural and gait disorders) contributed to decline in established patients. We conclude that within few years after diagnosis, PD patients show faster rate of cognitive decline than matched healthy subjects, particularly in domains of attention and psychomotor speed. Selection bias probably led to underestimation of the true extent of cognitive decline in established patients. (JINS, 2009, 15, 426–437.)
Effects of Environmental Cooling on Force Production in the Quadriceps and Hamstrings

The purpose of this study was to determine the effects of environmental cooling on force production in the quadriceps and hamstring muscles. Ten men (mean ± SD: age = 21.4 ± 2.2 years, height = 168.5 ± 35.9 cm, body mass = 78.0 ± 6.4 kg) participated in this study. Each subject completed 2 sets of 10 maximal effort repetitions on a Cybex II isokinetic dynamometer at 3.14 rad·s−1. Between sets, subjects sat in environmental temperatures of 20, 15, 10, or 5° C for 40 minutes. A significant decrease (p < 0.05) was observed in the pre- to postcooling peak torque values at 10° C and 5° C for both quadriceps and hamstrings. A significant decrease (p < 0.05) was also observed in the pre- to postcooling average torque values for the hamstrings at 10° C and 5° C. A significant increase (p < 0.05) in the amount of heat loss from the quadriceps and hamstrings occurred as environmental temperatures decreased. Force production of the quadriceps and hamstrings is significantly decreased when the body experiences environmental temperatures at or below 10° C for at least 40 minutes. A significant amount of heat loss also occurred from the quadriceps and hamstrings as environmental temperature decreased. The take-home message is that after a certain period of time exposed to cool ambient temperatures, performance may be decreased and warm-up time will increase.
Selective Ablation of Matrix Metalloproteinase-2 Exacerbates Experimental Colitis: Contrasting Role of Gelatinases in the Pathogenesis of Colitis1

The matrix metalloproteinases (MMPs), MMP-2 and MMP-9, share structural and substrate similarities and are up-regulated during human as well as animal models of inflammatory bowel disease. We recently demonstrated that epithelial-derived MMP-9 is an important mediator of inflammation and tissue damage in colitis. In this study, we examined the role of MMP-2 in acute colitis. Colitis was induced using two models, administration of dextran sodium sulfate (DSS) and Salmonella enterica subsp. serovar Typhimurium (S.T.). Bone marrow chimeras were performed using bone marrow cells from wild-type (WT) and MMP-2−/− mice. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, and histology. MMP-2 protein expression and activity were up-regulated in WT mice treated with DSS or S.T. MMP-2−/− mice were highly susceptible to the development of colitis induced by DSS (or S.T.) compared with WT. During inflammation, MMP-2 expression was increased in epithelial cells as well as in the infiltrating immune cells. Bone marrow chimera demonstrated that mucosa-derived MMP-2 was required for its protective effects toward colitis. Furthermore, we demonstrate that severe colitis in MMP-2−/− is not due to a compensatory increase in MMP-9. Finally, we show that MMP-2 regulates epithelial barrier function. In contrast to MMP-9, mucosa-derived MMP-2 may be a critical host factor that is involved in the prevention or cessation of the host response to luminal pathogens or toxins, an important aspect of healing and tissue resolution. Together, our data suggest that a critical balance between the two gelatinases determines the outcome of inflammatory response during acute colitis.
Risk factors for relinquishment of dogs to an animal shelter.

OBJECTIVE To identify canine and household characteristics associated with relinquishment of a pet dog to an animal shelter. DESIGN Case-control study. SAMPLE POPULATION Households that relinquished dogs for adoption (case households) and a random sample of current dog-owning households in the same community (control households). RESULTS Potentially modifiable factors that explained the highest proportion of relinquishment were owners not participating in dog obedience classes after acquisition, lack of veterinary care, owning a sexually intact dog, inappropriate care expectations, and dogs having daily or weekly inappropriate elimination. Dogs obtained from shelters, kept in crates, or acquired at > or = 6 months of age were at increased risk of relinquishment. Greater purchase price was associated with decreased risk of relinquishment, but relinquishment was not associated with the degree of planning to acquire the dog. Dogs with behavioral problems and little veterinary care were at greater risk of relinquishment than were dogs with regular veterinary care, and behavioral problems were associated with inappropriate care expectations. CLINICAL IMPLICATIONS Risk factors identified in this study can be modified by dog owners and veterinarians to decrease the estimated 2 million dogs euthanatized annually in animal shelters. Veterinarians should educate owners about typical dog behavior, routine care requirements and training, and the importance of regular veterinary visits; should incorporate wellness concepts in their practice; and should focus on preventive medicine and behavioral consultation.
Prolonged Suppression of Gonadotropin Secretion after Weight Recovery in an Anorectic Patient with Turner's Syndrome: Reduced Gonadal Function in Anorexia Nervosa is Independent in Part on Nutrition

Two hypotheses have been postulated as to the pathogenesis of hypogonadotropinemia in anorexia nervosa; one is starvation and weight loss and the other is a psychological factor to influence gonadotropin secretion. Our patient suffered from very rare concurrence of Turner's syndrome and anorexia nervosa and a study of this experiment in nature provided important evidences concerning decreased secretion of gonadotropins in the eating disorder. The patient was diagnosed as Turner's syndrome when she was 6 years old. Her gonadotropin levels were elevated to the castrated ranges (LH 61.8 IU/l; FSH 175.8 IU/l) after 8 years of age. She was noticed to be anorectic at the age of 13 years. Serum levels of the pituitary gonadotropins were lowered (LH 2.9 IU/l; FSH 3.0 IU/l) and their responses to luteinizing hormone-releasing hormone were decreased beneath the normal prepubertal limits. After one year of the anorectic period, she recovered the weight though her gonadotropin levels remained in the very low ranges (LH 2.7 IU/l; FSH 2.5 IU/l). The results suggest that hypogonadism in anorexia nervosa is not solely caused by nutritional deficiency but rather by other factors such as psychological abnormalities.
Collaborative Information Retrieval in R&D distributed teams

This research indicates how information retrieval activity is a social process helping to foster a network of organizational expertise. After describing knowledge management practices in a distributed research and development laboratory we identify recent introduction of Experts' Retrieval System (ERS). A four steps model RESONER: Information Retrieval, Caring (social support), Negotiation, and Reification is suggested. This model specifies DemonD an ERS relying on transparent profile construction based on user's activity, community's participation and shared documents. DemonD eventually encourages the emergence of informal knowledge networks and competencies awareness in a distributed context.
Single- and Multi-Wall Carbon Nanotubes Versus Asbestos: Are the Carbon Nanotubes a New Health Risk to Humans?

Carbon nanotubes (CNT), since their discovery, have become one of the most promising nanomaterials in many industrial and biomedical applications. Due to their unique physicochemical properties, interest is growing in the manufacture of CNT-based products and their subsequent marketing. Since their discovery, the prospect of possible undesirable human health effects has been a focus of many scientific studies. Although CNT possess unique physical properties that include (1) nanoscale diameter, (2) a wide length distribution ranging from tens of nanometers to several micrometers, and (3) high aspect ratio, the fibrous-like shape and durability suggest that their toxic properties may be analogous to those observed with other fibrous particles, such as asbestos. The present study provides a summary of published findings on CNT bioactivity, such as the potential of CNT, especially of multi-wall carbon nanotubes (MWCNT), to activate signaling pathways modulating transcription factor activity, induce apoptosis, induce DNA damage, and initiate biological responses. Assessment of risks to human health and adoption of appropriate exposure controls is critical for the safe and successful introduction of CNT -based products for future applications.
A Supervised Feature Projection for Real-Time Multifunction Myoelectric Hand Control

EMG pattern recognition is essential for the control of a multifunction myoelectric hand. The main goal of this study is to develop an efficient feature projection method for EMG pattern recognition. To this end, we propose a linear supervised feature projection that utilizes linear discriminant analysis (LDA). We first perform wavelet packet transform (WPT) to extract the feature vector from four channel EMG signals. For dimensionality reduction and clustering of the WPT features, the LDA incorporates class information into the learning procedure and finds a linear matrix to maximize the class separability for the projected features. Finally, the multilayer perceptron (MLP) classifies the LDA-reduced features into nine hand motions. To evaluate the performance of LDA for the WPT features, we compare LDA with three other feature projection methods. From a visualization and quantitative comparison, we show that LDA has better performance for the class separability, and the LDA-projected features improve the classification accuracy with a short processing time. We implemented a real-time control system for a multifunction myoelectric hand. In experiment, we show that the proposed method achieves 97.2% recognition accuracy, and that all processes, including the myoelectric hand control, are completed within 97 msec
Reactive Oxygen Species– and DNA Damage Response–Dependent NK Cell Activating Ligand Upregulation Occurs at Transcriptional Levels and Requires the Transcriptional Factor E2F1

Increasing evidence indicates that cancer cell stress induced by chemotherapeutic agents promote antitumor immune responses and contribute to their full clinical efficacy. In this article, we identify the signaling events underlying chemotherapy-induced NKG2D and DNAM-1 ligand expression on multiple myeloma (MM) cells. Our findings indicate that sublethal doses of doxorubicin and melphalan initiate a DNA damage response (DDR) controlling ligand upregulation on MM cell lines and patient-derived malignant plasma cells in Chk1/2-dependent and p53-independent manner. Drug-induced MICA and PVR gene expression are transcriptionally regulated and involve DDR-dependent E2F1 transcription factor activity. We also describe the involvement of changes in the redox state in the control of DDR-dependent upregulation of ligand surface expression and gene transcriptional activity by using the antioxidant agent N-acetyl-l-cysteine. Finally, in accordance with much evidence indicating that DDR and oxidative stress are major determinants of cellular senescence, we found that redox-dependent DDR activation upon chemotherapeutic treatment is critical for MM cell entry in premature senescence and is required for the preferential ligand upregulation on senescent cells, which are preferentially killed by NK cells and trigger potent IFN-γ production. We propose immunogenic senescence as a mechanism that promotes the clearance of drug-treated tumor cells by innate effector lymphocytes, including NK cells.
ERP data archiving - a critical analysis

ERP (enterprise resource planning) systems run on top of database systems, like Oracle, SQL Server and DB2. The longer these systems are in place within organizations the larger the databases are. Some sources estimate that corporate databases double or triple in size every year. As these databases grow, performance, the time it takes to complete transactions, is adversely affected. This implies that limiting the amount of data stored on an ERP system is an essential element of proper storage and data management. However, removing data from an ERP system can be a complex and risky task. Archiving ERP data is an area of academic and professional research that has had minimal attention. This paper examines the issues and provides insight into solutions associated with archiving ERP data. The issues are explored by summarizing the limited background and research in the archiving area, followed by an overview of the methodology used to arrive at the case study approach used to gather the data. Case data are presented from three different large corporate environments and the results of the data are used to recommend an archiving strategy that other companies can follow. A discussion of the implications of the proposed archiving strategy for future use and research concludes the paper.
Anti-vascular endothelial growth factor therapy for ocular neovascular disease

Purpose of review Recent research has shown that vascular endothelial growth factor (VEGF) is responsible for many ocular pathologies involving neovascularization. Over the past several years several new agents targeting VEGF have become commercially available for intraocular use. These agents have revolutionized the care of neovascular age related macular degeneration and have great potential for other blinding conditions such as diabetic retinopathy, retinopathy of prematurity, and neovascular glaucoma. Recent findings The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial first showed that an anti-VEGF agent (pegaptanib) was able to prevent vision loss in neovascular age related macular degeneration. The Minimally Classic/Occult Trial of Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials showed that ranibizumab prevented moderate vision loss in neovascular age related macular degeneration and for the first time that a substantial proportion of patients regained vision. Smaller case series have shown that bevacizumab can regress retinal, iris and disc neovascularization. Ongoing trials are investigating the utility of anti-VEGF therapy in retinopathy of prematurity, diabetic retinopathy, and neovascular glaucoma. Summary Newer anti-VEGF therapies have shown unprecedented efficacy in treating age related macular degeneration with many patients experiencing improvement in vision. Ongoing trials will help guide their use in age related macular degeneration and expand their indications to many other blinding diseases.
Characterization and molecular basis of the oligomeric structure of HIV‐1 Nef protein

The Nef protein of human immunodeficiency virus type I (HIV‐1) is an important determinant for the onset of AIDS disease. The self‐association properties of HIV‐1 Nef are analyzed by chemical cross‐linking, dynamic light scattering, equilibrium analytical ultracentrifugation, and NMR spectroscopy. The experimental data show that the HIV‐1 Nef core domain forms stable homo‐dimers and trimers in solution, but not higher oligomers. These Nef homomers are not covalently linked by disulfide bridges, and the equilibrium between these forms is dependent on the Nef concentration. We further provide the molecular basis for the Nef core dimers and trimers obtained by analysis of crystallographic models. Oligomerization of biological polypeptides is a common tool used to trigger events in cellular signaling and endocytosis, both of which are targeted by Nef. The quaternary structure of Nef may be of physiological importance and may help to connect its cellular targets or to increase affinity of the viral molecule for its ligands. The herein described models for Nef dimers and trimers will allow further mutational studies to elucidate their role in vivo. These results provide novel insight into the structural and functional relationships of this important viral protein. Moreover, the oligomer interface may represent a novel target for the design of antiviral agents.
In vitro and in vivo evaluation of macromolecular prodrug GC-FUA based nanoparticle for hepatocellular carcinoma chemotherapy

Abstract A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague–Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.