Miracle-dz/UniFAR-FTUs huggingface dataset:
Educational approaches to prescribing practices and substance abuse.

The history of medical education in treating and prescribing for additive disorders is primarily one of omission. This began to change in the 1970s, leading to positive developments in medical education; however, much still remains to be done. Training in writing prescriptions should cover four areas: (1) prescribing to prevent addiction; (2) prescribing for alcohol or other drug dependent patients; (3) prescribing for withdrawal from alcohol or other drugs; and (4) prescribing for patients in recovery from alcohol or other drug addiction. Other areas of importance to medical education are inappropriate prescribing practices, self-prescribing, and prescribing for dual diagnosis patients. Physicians need to know how to avoid becoming duped, dated, impaired or "script doctors. " The educational techniques used in attaining these goals emphasize adult, or andragogical, education, sequencing curricula over the years of medical school and residency training, utilizing a variety of instructional techniques, and evaluating the results after each educational unit. The use of clinical vignettes, patient management problems and simulated patients is recommended.
Diesel exhaust particles and airway inflammation

Purpose of review Epidemiologic investigation has associated traffic-related air pollution with adverse human health outcomes. The capacity of diesel exhaust particles (DEPs), a major emission source air pollution particle, to initiate an airway inflammation has subsequently been investigated. We review the recent controlled human exposures to diesel exhaust and DEPs, and summarize the investigations into the associations between this emission source air pollution particle and airway inflammation. Recent findings Using bronchoalveolar lavage, bronchial biopsies, and sputum collection, studies have demonstrated inflammation in the airways of healthy individuals after exposure to diesel exhaust and DEPs. This inflammation has included neutrophils, eosinophils, mast cells, and lymphocytes. Elevated expression and concentrations of inflammatory mediators have similarly been observed in the respiratory tract after diesel exhaust and DEP exposure. An increased sensitivity of asthmatic individuals to the proinflammatory effects of DEPs has not been confirmed. Summary Inflammation after diesel exhaust and DEP exposure is evident at higher concentrations only; there appears to be a threshold dose for DEPs approximating 300 &mgr;g/m3. The lack of a biological response to DEPs at lower concentrations may reflect a contribution of gaseous constituents or interactions between DEPs and gaseous air pollutants to the human inflammatory response and function loss.
Optimum treatment for mediastinal lymph node positive (N2) resectable non-small cell lung cancer: what is the role for surgery?

ABSTRACT Introduction: A third of patients with Non-Small Cell Lung Cancer (NSCLC) present with Stage III disease with mediastinal (N2) nodal involvement representing an extremely heterogeneous population with a generally poor prognosis. Areas covered: This article describes the complexity of Stage III-N2 patients reviewing the outcomes of key clinical trials while highlighting the trial designs and subtleties that have created controversy in management. Both bimodality approaches combining chemotherapy with either surgery or radiation and trimodality approaches combining chemotherapy with both local therapies are reviewed. Finally, prognostic factors and future directions are explored for the management of this population. Expert commentary: Upfront surgery is not recommended for patients with Stage III-N2 NSCLC. Neoadjuvant approaches with both chemotherapy and chemoradiation are acceptable in a multidisciplinary setting if appropriate surgery is performed by a dedicated thoracic surgeon. Non-operative candidates should receive definitive concurrent chemoradiation. Innovative approaches are necessary to improve outcomes in this population.
Assessment of the cancer potential of methanol

There are no published cancer studies of methanol-exposed cohorts. Genotoxicity studies do not suggest carcinogenic activity from methanol exposure. Oncogenicity studies of methanol were conducted by inhalation for ~20 hrs/day at up to 1000 ppm in F344 rats and B6C3F1 mice (NEDO), and by incorporation into drinking water at up to 20,000 ppm in Sprague-Dawley rats (Ramazzini Foundation, by Soffritti et al.). No increased neoplasms were found in the NEDO rat and mouse inhalation studies, even at air levels (up to 1000 ppm for >19 hours/day, 7 days/week) that caused 10-fold increased blood methanol levels. The maximum dose level was 600 mg/kg/day. The breakdown of methanol to formaldehyde in rats is saturated at doses above 600 mg/kg according to Horton et al. Thus, higher inhalation exposure concentrations are not expected to lead to tumors in rats or mice. In the Soffritti et al. study there was excessive early mortality, and lung pathology (inflammation, dysplasia, or neoplasm) was present in 87–94% of those dying anytime in the study. Soffritti et al. reported lympho-immunoblastic lymphoma. There are no historical control data to which this study can be compared because this diagnosis is not used by any other pathologist in animal studies. Lung infections probably played a role in formation of the lesions called lympho-immunoblastic lymphoma in the Ramazzini methanol study. The data from genotoxicity studies, the inhalation and drinking water oncogenicity studies of methanol in rats and mice, and mode of action considerations support a conclusion that methanol is not likely to be carcinogenic in humans.
The Cell Biology of Hermansky–Pudlak Syndrome: Recent Advances

Hermansky–Pudlak syndrome (HPS) defines a group of at least seven autosomal recessive disorders characterized by albinism and prolonged bleeding. These manifestations arise from defects in the biogenesis of lysosome‐related organelles, including melanosomes and platelet dense granules. Most genes associated with HPS in humans and rodent models of the disease encode components of multisubunit protein complexes that are expressed ubiquitously and play roles in intracellular protein trafficking and/or organelle distribution. A small GTPase of the Rab family, Rab38, is also implicated in the pathogenesis of the disease. This article reviews recent progress toward elucidating the cellular functions of these proteins.
A beginner’s guide to reviewing manuscripts in ecology and conservation

Peer review is a hallmark of scientific publishing, yet finding peers to conduct reviews is increasingly challenging. Some attribute this challenge to the “tragedy of the referee commons,” wherein selfish behaviors related to the publication of scientific manuscripts lead to unsustainable use of potential referees and a reduction in the quality of scientific publications. To address the tragedy and maintain the quality of scientific publications, we could increase the degree to which junior referees are involved in the peer review process. Because these potential referees often have limited relevant experience and limited access to useful resources, we have developed a guide to reviewing manuscripts submitted for publication in journals that focus on conservation, ecology, or evolution. Herein, we provide an overview of the peer review process, discuss the role of junior reviewers in this process, and discuss how reviews should be conducted. This guide can serve to train both new and junior referees as well as to provide a refresher for senior referees.
Comparative virulence of opacity variants of Neisseria gonorrhoeae strain P9

The invasive properties of nine variants of Neisseria gonorrhoeae strain P9 known to vary in their surface composition have been investigated. Relative virulence was evaluated by their cytotoxic effect on Chang epithelial cell monolayers. Piliated variants P9-2 (with alpha pili) and P9-20 (with beta pili plus protein II) showed increased ability to kill the target cells compared with the prototype P9-1 (lacking pili and additional outer membrane proteins). Two nonpiliated variants, P9-11 (with proteins IIa and IId) and P9-19 (with proteins II and IIc), were also relatively more virulent compared with P9-1. Enhanced attachment was exhibited by both piliated and some nonpiliated variants: beta-piliated P9-20 (with protein II; molecular weight, 29,000) and nonpiliated P9-16 (with protein IIb; molecular weight, 28,000) were the most effective in adherence to the target monolayers.
Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: a novel class of bioactive molecules

Short oligonucleotides below 8–10 nt in length adopt relatively simple structures. Accordingly, they represent interesting and so far unexplored lead compounds as molecular tools and, potentially, for drug development as a rational improvement of efficacy seem to be less complex than for other classes of longer oligomeric nucleic acid. As a ‘proof of concept’, we describe the highly specific binding of the hexanucleotide UCGUGU (Hex-S3) to human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) as a model target. Ultraviolet (UV) cross-linking studies and competition experiments with primer/template substrates and a RT-directed aptamer suggest site-specific binding of Hex-S3 to the large subunit (p66) of the viral enzyme. The affinity of 5.3 μM is related to hexanucleotide-specific suppression of HIV-1 replication in human cells by up to three orders of magnitude indicating that Hex-S3 exerts specific and biologically relevant activity. Experimental evidence described here further suggests a systematic hexamer array-based search for new tools for molecular biology and novel lead compounds in nucleic acid-based drug development.
Facilitating Medical Ethics Case Review: What Ethics Committees Can Learn from Mediation and Facilitation Techniques

Medical ethics committees are increasingly called on to assist doctors, patients, and families in resolving difficult ethics issues. Although committees are becoming more sophisticated in the substance of medical ethics, little attention has been given to the processes these committees use to facilitate decision-making. In 1990, the National Institute for Dispute Resolution in Washington, D.C., provided a planning grant from its Innovation Fund to the Institute of Public Law of the University of New Mexico School of Law to look at what ethics committees can learn from facilitation and mediation techniques. The study's thesis was that, if adapted for use by medical ethics committees, facilitation and mediation techniques can be helpful to those bodies in case review consultations and in other internal committee processes. This article reports on that project.
Virtual perambulator: a novel interface device for locomotion in virtual environment

Walkthrough simulation is effective for design and presentation of buildings or urban space. The paper presents a method of implementing a new interface device for locomotion in virtual space. The walker wears omni directional sliding devices on the feet, which generate the feel of walking while the position of the walker is fixed in the physical world. A hoop is set around the walker's waist, by which the position of the walker is limited. The walker can freely change the direction of walking in the hoop. The scene of virtual space is displayed in a head mounted display, corresponding with the motion of the feet and head. Usability of the system is tested by 235 novice users at SIGGRAPH'95. 94% of the participants could walk freely around the virtual space.
Adaptive Filtering for Stochastic Volatility by using Exact Sampling

We study the sequential identification problem for Bates stochastic volatility model, which is widely used as the model of a stock in finance. By using the exact simulation method, a particle filter for estimating stochastic volatility is constructed. The systems parameters are sequentially estimated with the aid of parallel filtering algorithm. To improve the estimation performance for unknown parameters, the new resampling procedure is proposed. Simulation studies for checking the feasibility of the developed scheme are demonstrated.
Association between the IL-6 rs 1800796 (-572 C / G ) polymorphism and chronic obstructive pulmonary disease risk : a meta-analysis

Interleukin-6 (IL-6), a pleiotropic proinflammatory and immunomodulatory cytokine, is highly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Thus we conducted a meta-analysis to investigate the relationship between the IL-6 rs1800796 (-572C/G) polymorphism and COPD risk. We conducted a literature search up to April 20, 2015, using the PubMed, Embase and Chinese National Knowledge Infrastructure (CNKI) databases. Studies published in languages other than English or Chinese were excluded. A total of 413 COPD cases and 596 controls in 3 case-control studies were included in this study. The results of our meta-analysis suggested that the IL-6 rs1800796 (-572C/G) was significantly associated with COPD in a codominant genetic model (GC vs. GG, OR: 0.45, 95% CI: 0.28-0.72; CC vs. GG, OR: 0.20, 95% CI: 0.09-0.46). Moreover, no publication bias was detected in this study.
Attachment of the Ubiquitin-Related Protein Urm1p to the Antioxidant Protein Ahp1p

ABSTRACT Urm1p is a ubiquitin-related protein that serves as a posttranslational modification of other proteins. Urm1p conjugation has been implicated in the budding process and in nutrient sensing. Here, we have identified the first in vivo target for the urmylation pathway as the antioxidant protein Ahp1p. The attachment of Urm1p to Ahp1p requires the E1 for the urmylation pathway, Uba4p. Loss of the urmylation pathway components results in sensitivity to a thiol-specific oxidant, as does loss of Ahp1p, implying that urmylation has a role in an oxidative-stress response. Moreover, treatment of cells with thiol-specific oxidants affects the abundance of Ahp1p-Urm1p conjugates. These results suggest that the conjugation of Urm1p to Ahp1p could regulate the function of Ahp1p in antioxidant stress response in Saccharomyces cerevisiae.
DNA Binding Properties of Peroxisome Proliferator-activated Receptor Subtypes on Various Natural Peroxisome Proliferator Response Elements

The three subtypes of the peroxisome proliferator-activated receptors (PPARα, β/δ, and γ) form heterodimers with the 9-cis-retinoic acid receptor (RXR) and bind to a common consensus response element, which consists of a direct repeat of two hexanucleotides spaced by one nucleotide (DR1). As a first step toward understanding the molecular mechanisms determining PPAR subtype specificity, we evaluated by electrophoretic mobility shift assays the binding properties of the three PPAR subtypes, in association with either RXRα or RXRγ, on 16 natural PPAR response elements (PPREs). The main results are as follows. (i) PPARγ in combination with either RXRα or RXRγ binds more strongly than PPARα or PPARβ to all natural PPREs tested. (ii) The binding of PPAR to strong elements is reinforced if the heterodimerization partner is RXRγ. In contrast, weak elements favor RXRα as heterodimerization partner. (iii) The ordering of the 16 natural PPREs from strong to weak elements does not depend on the core DR1 sequence, which has a relatively uniform degree of conservation, but correlates with the number of identities of the 5′-flanking nucleotides with respect to a consensus element. This 5′-flanking sequence is essential for PPARα binding and thus contributes to subtype specificity. As a demonstration of this, the PPARγ-specific element ARE6 PPRE is able to bind PPARα only if its 5′-flanking region is exchanged with that of the more promiscuous HMG PPRE.
Dynamic Factor Analysis For Panel Data: A Generalized Model

We develop a generalized dynamic factor model for panel data with the goal of estimating an unobserved performance index. While similar models have been developed in the literature of dynamic factor analysis, our contribution is threefold. First, contrary to simple dynamic factor analysis where multiple attributes of the same cross sectional unit are measured at each time period, our model also accounts for multiple cross sectional units. It is therefore applicable to a panel data framework (i.e. multiple attributes for multiple cross sectional units observed over time). Second, our model estimates an unobserved index for every cross sectional unit for every time period, as opposed to previous work where a ∗The authors would like to thank Alexander Danilenko for providing data from the International Benchmarking Network. We are grateful to John Buonaccorsi, Klaus Moeltner, Joe Moffitt and John Stranlund for their constructive feedback.Comments and suggestions from seminar participants at the University of Ottawa and the University of Massachusetts Amherst are greatly appreciated. This research was made possible with funding by the NIH grant AG13846. Any remaining errors are ours. †School of Public and Environmental Affairs, Indiana University, nzirogia@indiana.edu. ‡Department of Biostatistics, Boston University, yorghos@bu.edu.
Does sporadic Listeria gastroenteritis exist? A 2-year population-based survey in Nova Scotia, Canada.

BACKGROUND Febrile gastroenteritis due to Listeria monocytogenes (LM) has been primarily described in foodborne outbreaks. We decided to determine the incidence of sporadic, febrile gastroenteritis due to LM in a large, well-defined North American population over a 2-year period and to compare these cases to sporadic cases of Campylobacter and Salmonella infections occurring concurrently in the community. METHODS From 1 September 2002 through 31 August 2004, all stool specimens submitted for evaluation of diarrheal illness to a public health laboratory and to a children's hospital serving a population of approximately 350,000 were examined for the presence of Listeria species. Patients identified as having LM in their stool samples were matched with 2 temporally-matched patients with cultures positive for Campylobacter and Salmonella species. Patients with LM and control patients were contacted by telephone, and they answered a questionnaire that examined clinical features and risk factors for diarrheal illness. RESULTS A total of 7775 stool specimens were submitted during the period 1 September 2002-31 August 2004. Thirty-nine Listeria species were recovered. Seventeen of the species were LM, 13 were Listeria innocua, 3 were Listeria welshimeri, 1 was Listeria grayi, and 4 were other species. Pulsed-field gel electrophoresis results demonstrated no temporal or other clusters, and no seasonality was noted for isolates of LM. Preexisting gastrointestinal problems were much more common in patients with LM (P=.001) than in patients with Campylobacter or Salmonella infections. CONCLUSIONS Sporadic gastroenteritis due to LM appears to be an uncommon illness, and routine screening of stool samples for LM remains unwarranted. Preexisting gastrointestinal disease may be a risk factor for infection of the gastrointestinal tract with LM.
Replication and Translation of Sperm-introduced Hepatitis B Virus Genesin Embryonic Cells

Objective: Given that hepatitis B virus (HBV) can infect human sperm cells and HBV genes introduced by sperm can be transcribed in developing embryos, we sought to confirm the presence of mature HBV antigens and to assess the mechanism of viral gene replication in embryonic cells. Methods: Human sperm were transfected with recombinant plasmids pIRES2-EGFP-HBs or pIRES2-EGFP-HBc and were then used to fertilize zona-free golden hamster ova. Two-celled embryos with and without green fluorescence were collected for detection of HBV DNA or protein by fluorescence in situ hybridization (FISH), immunofluorescence assay (IA), and enzyme-linked immunosorbent assay (ELISA). Results: 1. Positive FISH signals for HBs- and HBc-DNA were observed in the sperm nuclei and in the nuclei of the two-celled embryos in the test samples but were not detected in the controls. 2. Positive IA signals for HBsAg or HBcAg were detected within the cytoplasm of the two-celled embryos in the test samples but not in the controls. 3. Using ELISA, the level of HBsAg in a single two-celled embryo was 0.064 ng/ ml. Likewise, HBcAg was detected in the five-embryo experimental group. Conclusion: The sperm-introduced HBV S or C genes were able to replicate concomitantly host embryo genome via a semiconservative mode of DNA replication and were able to express viral proteins in the embryonic cells.
The Proprotein Convertase PCSK9 Induces the Degradation of Low Density Lipoprotein Receptor (LDLR) and Its Closest Family Members VLDLR and ApoER2*

The proprotein convertase PCSK9 gene is the third locus implicated in familial hypercholesterolemia, emphasizing its role in cardiovascular diseases. Loss of function mutations and gene disruption of PCSK9 resulted in a higher clearance of plasma low density lipoprotein cholesterol, likely due to a reduced degradation of the liver low density lipoprotein receptor (LDLR). In this study, we show that two of the closest family members to LDLR are also PCSK9 targets. These include the very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) implicated in neuronal development and lipid metabolism. Our results show that wild type PCSK9 and more so its natural gain of function mutant D374Y can efficiently degrade the LDLR, VLDLR, and ApoER2 either following cellular co-expression or re-internalization of secreted human PCSK9. Such PCSK9-induced degradation does not require its catalytic activity. Membrane-bound PCSK9 chimeras enhanced the intracellular targeting of PCSK9 to late endosomes/lysosomes and resulted in a much more efficient degradation of the three receptors. We also demonstrate that the activity of PCSK9 and its binding affinity on VLDLR and ApoER2 does not depend on the presence of LDLR. Finally, in situ hybridization show close localization of PCSK9 mRNA expression to that of VLDLR in mouse postnatal day 1 cerebellum. Thus, this study demonstrates a more general effect of PCSK9 on the degradation of the LDLR family that emphasizes its major role in cholesterol and lipid homeostasis as well as brain development.
Cyclins and the Wiring of the Yeast Cell Cycle

The yeast cell cycle 1635 Start 1635 The cyclins of Succharomyces cerevisiae 1636 Waves of cyclin expression orchestrate cell cycle events 1637 A cyclin cascade in GI 1637 Nutrients, growth rates and Cln thresholds 1639 Proteolysis in the yeast cell cycle 1640 Sic1 and the dependence of S-Phase on Start 1642 Control of Clb2 expression and activity 1643 Over-view: Switches for re-setting the cycle 1643 References 1644
Colorectal cancer test use among persons aged > or = 50 years--United States, 2001.

Colorectal cancer is the second leading cause of cancer-related death in the United States. The lifetime risk for having colorectal cancer diagnosed is 6%. Screening measures decrease the incidence and mortality of colorectal cancer by detecting early disease and removing precancerous lesions. The U.S. Preventive Services Task Force recommends routine cancer screening for U.S. adults aged > or = 50 years with one or a combination of the following screening options: annual home fecal occult blood testing (FOBT), sigmoidoscopy every 5 years, colonoscopy every 10 years, or double contrast barium enema every 5 years. To estimate rates and evaluate trends for colorectal cancer test use among U.S. adults aged > or = 50 years, CDC analyzed data from the 2001 Behavioral Risk Factor Surveillance System (BRFSS) on the use of FOBT and sigmoidoscopy/colonoscopy and compared the data for 2001 with those for 1997 and 1999. This report summarizes the results of that analysis, which indicate that despite small increases in the self-reported use of colorectal cancer tests, screening rates remain low. Efforts to increase awareness and encourage regular colorectal cancer screening should continue.