Miracle-dz/UniFAR-FTUs huggingface dataset:
Markers for trans-Golgi Membranes and the Intermediate Compartment Localize to Induced Membranes with Distinct Replication Functions in Flavivirus-Infected Cells

ABSTRACT Replication of the flavivirus Kunjin virus is associated with virus-induced membrane structures within the cytoplasm of infected cells; these membranes appear as packets of vesicles associated with the sites of viral RNA synthesis and as convoluted membranes (CM) and paracrystalline arrays (PC) containing the components of the virus-specified protease (E. G. Westaway, J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A. Khromykh, J. Virol. 71:6650–6661, 1997). To determine the cellular origins of these membrane structures, we compared the immunolabelling patterns of several cell markers in relation to these sites by immunofluorescence and immunoelectron microscopy. A marker for the trans-Golgi membranes and the trans-Golgi network, 1,4-galactosyltransferase (GalT), was redistributed to large foci in the cytoplasm of Kunjin virus-infected cells, partially coincident with immunofluorescent foci associated with the putative sites of viral RNA synthesis. As determined by immunoelectron microscopy, the induced vesicle packets contained GalT, whereas the CM and PC contained a specific protein marker for the intermediate compartment (ERGIC53). A further indicator of the role of cellular organelles in their biogenesis was the observation that the Golgi apparatus-disrupting agent brefeldin A prevented further development of immunofluorescent foci of induced membranes if added before the end of the latent period but that once formed, these membrane foci were resistant to brefeldin A dispersion. Reticulum membranes emanating from the induced CM and PC were also labelled with the rough endoplasmic reticulum marker anti-protein disulfide isomerase and were obviously redistributed during infection. This is the first report identifyingtrans-Golgi membranes and the intermediate compartment as the apparent sources of the flavivirus-induced membranes involved in events of replication.
Does Coronary Endarterectomy Increase the Risk of Coronary Bypass?

Abstract Background: With increased incidence of angioplasty and stent implantation, patients referred for coronary bypass (CABG) typically have more advanced and diffuse coronary disease. Thus, more patients may require endarterectomy in order to achieve complete revascularization. We compared our results in patients undergoing CABG with or without coronary endarterectomy. Methods: Between 1993 and 1999, 2372 patients underwent isolated CABG in our department. A retrospective analysis was performed to compare patients requiring coronary endarterectomy of the LAD (group 1, n #88), endarterectomy of arteries other than the LAD (group 2, n #143), to those not requiring endarterectomy (group 3, n # 2071). Patients undergoing CABG without the use of cardiopulmonary bypass were excluded. Group 1 had a higher incidence of proximal LAD stenosis (p #0.001) than group 3, while group 2 had a higher incidence of peripheral vascular disease (p #0.02), preoperative Ml (p # 0.03) and LV dysfunction (p = 0.001). Results: Operative mortality was 10% in group 1 (p < 0.001) and 4% in group 2 (p #IMS) compared to 3% in group 3. Incidence of perioperative Ml was 12% in group 1 (p # 0.001) and 8% in group 2 (p # 0.001) compared to 2% in group 3. Conclusions: Patients requiring endarterectomy of the LAD are at increased risk of operative mortality. This was not true for patients requiring endarterectomy of arteries other than the LAD. In both groups there was an increased risk of perioperative myocardial infarction.
Paracetamol for low back pain.

BACKGROUND Analgesic medication is the most frequently prescribed treatment for low back pain (LBP), of which paracetamol (acetaminophen) is recommended as the first choice medication. However, there is uncertainty about the efficacy of paracetamol for LBP. OBJECTIVES To investigate the efficacy and safety of paracetamol for non-specific LBP. SEARCH METHODS We conducted searches on the Cochrane Central Register of Controlled Trials (CENTRAL, which includes the Back and Neck Review Group trials register), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, LILACS, and IPA from their inception to 7 August 2015. We also searched the reference lists of eligible papers and trial registry websites (WHO ICTRP and ClinicalTrials.gov). SELECTION CRITERIA We only considered randomised trials comparing the efficacy of paracetamol with placebo for non-specific LBP. The primary outcomes were pain and disability. We also investigated quality of life, function, adverse effects, global impression of recovery, sleep quality, patient adherence, and use of rescue medication as secondary outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently performed the data extraction and assessed risk of bias in the included studies. We also evaluated the quality of evidence using the GRADE approach. We converted scales for pain intensity to a common 0 to 100 scale. We quantified treatment effects using mean difference for continuous outcomes and risk ratios for dichotomous outcomes. We used effect sizes and 95% confidence intervals as a measure of treatment effect for the primary outcomes. When the treatment effects were smaller than 9 points on a 0 to 100 scale, we considered the effect as small and not clinically important. MAIN RESULTS Our searches retrieved 4449 records, of which three trials were included in the review (n = 1825 participants), and two trials were included in the meta-analysis. For acute LBP, there is high-quality evidence for no difference between paracetamol (4 g per day) and placebo at 1 week (immediate term), 2 weeks, 4 weeks, and 12 weeks (short term) for the primary outcomes. There is high-quality evidence that paracetamol has no effect on quality of life, function, global impression of recovery, and sleep quality for all included time periods. There were also no significant differences between paracetamol and placebo for adverse events, patient adherence, or use of rescue medication. For chronic LBP, there is very low-quality evidence (based on a trial that has been retracted) for no effect of paracetamol (1 g single intravenous dose) on immediate pain reduction. Finally, no trials were identified evaluating patients with subacute LBP. AUTHORS' CONCLUSIONS We found that paracetamol does not produce better outcomes than placebo for people with acute LBP, and it is uncertain if it has any effect on chronic LBP.
Investigating human behaviors in selecting personal photos to preserve memories

Photos are excellent means for keeping and refreshing memories. Digital photography, however, imposes new challenges for keeping photos accessible on the long run due to threats such as hard disk crashes, format changes, or storage medium decay. Safe long-term preservation, ensuring the longevity of photos, comes at a cost, suggesting a restriction of this investment to the most valuable photos. Therefore, understanding how people behave when selecting their most valuable photos from large collections is an important first step towards the development of automatic preservation approaches. In this paper, we conduct a user study of 35 participants in selecting personal photos for long-term preservation. The results of the study provide insights for the photo selection process. In addition, we propose a photo selection method based on machine learning and compared human selections with leading edge clustering techniques, highlighting significant issues in emulating human decision patterns.
Improving Outpatient Antibiotic Prescribing for Respiratory Tract Infections: Results of New Algorithms Used in European Trials

In September 2014, the US “National Strategy for Combating Antibiotic Resistant Bacteria” was released in accordance with a 2013 Presidential mandate. An overarching goal is reduction in the unnecessary use of antibiotics to help slow down the emergence of antibiotic-resistant bacteria and extend the useful life of existing antibiotics. The strategy calls for expansion and monitoring of antibiotic stewardship programs and advancement of the development and use of rapid diagnostic tests—including those that distinguish between viral and bacterial infections. This review article discusses the challenges to US physicians in diagnosing respiratory tract infections (RTIs) and considers opportunities to optimize antibiotic use in outpatient settings, including the use of point-of-care testing. The potential of a point-of-care diagnostic test, such as C-reactive protein (CRP), is discussed through a review of the European Union experience and opinions of US and international experts gained at a meeting of the Alliance for the Prudent Use of Antibiotics titled Improving Antimicrobial Stewardship in Outpatient Settings: Potential for Biomarkers Such as CRP, held on May 21, 2014, in Boston, Massachusetts.
Superantigens augment antigen‐specific Th1 responses by inducing IL‐12 production in macrophages

Superantigens (SAg) are microbial proteins that mediate antigen‐presenting cell (APC)‐T cell interaction by cross‐linking MHC class II molecules with subsets of TcRVβ. SAgs are implicated in the pathogenesis of several infectious, inflammatory, and autoimmune diseases. In this study, we examined the influence of SEB on interleukin‐12 (IL‐12) production and the activation of antigen‐specific Th1 responses. Addition of SEB augmented the antigen‐induced proliferation of HS‐17, a murine MBPp91‐103 peptide‐specific TcRVβ6+ CD4+ Th1 clone. SEB augments HS‐17 T cell proliferation through its interaction with IAs molecules on macrophages, but not with the TcRVβ6 on HS‐17 cells. On binding to IAs, SEB induces IL‐12 production in macrophages, which in turn augments antigen‐induced proliferation of HS‐17 T cells. Treatment with anti‐IAs mAb 10‐3.6 inhibited the antigen‐ and SEB‐induced IL‐12 production and T cell proliferation. These results suggest that SAgs augment antigen‐specific T cell responses by inducing IL‐12 production in macrophages. J. Leukoc. Biol. 65: 665–670; 1999.
Investigation of SUMO pathway genes in the etiology of nonsyndromic cleft lip with or without cleft palate.

BACKGROUND SUMO1 has been implicated as having a role in the causation of cleft lip with or without cleft palate (CLP), both directly and through association studies in humans and, perhaps more controversially, in transgenic mouse studies. METHODS To screen for sequence variants that might be responsible for human CLP, we performed direct DNA sequence analysis in a well-characterized white European cohort of 192 patients. We screened the genes encoding SUMO1, SUMO2, and SUMO3, as well as the E3 ligases PIAS1 and PIAS2, which are required for sumoylation. Variants were analyzed in a cohort of 192 unaffected white European controls. RESULTS Only two missense variants were identified, both within SUMO3, however, these were both present in multiple affected individuals and a similar number of controls. Other variants identified, apart from a single synonymous change in PIAS1, were all present within flanking intronic regions distant from splice consensus sites. Moreover, most other variants were previously reported in dbSNP and were shown to be present at a similar frequency in cases and controls. CONCLUSIONS Our findings indicate that mutations identified in the SUMO-related genes tested, including three novel coding SNPs, do not directly contribute to the incidence of CLP.
Therapeutic implications of the vasoprotective axis of the renin-angiotensin system in cardiovascular diseases.

The recent discovery of angiotensin-converting enzyme 2 (ACE2) and the Mas receptor has resulted in the recognition of a counterregulatory, ACE2/Ang-(1-7)/Mas, axis within the renin-angiotensin system (RAS). Any disturbance in the balance between this and the ACE/AngII/AT1 receptor axis is suggested to lead to the development and progression of cardiovascular disease (CVD). Therefore, activation of the ACE2/Ang-(1-7)/Mas axis has been an obvious target for CVD therapeutics. In this review, we will focus on the current status of the RAS, highlight evidence for the existence of the ACE2/Ang-(1-7)/Mas axis, and discuss, the role of this axis in the pathophysiology of the cardiovascular, renal, pulmonary and central nervous systems and its potential for future CVD therapeutics.
Actions of the torus on 4-manifolds. I

Smooth actions of the 2-dimensional torus group SO(2) x 50(2) on smooth, closed, orientable 4-manifolds are studied. A cross-sectioning theorem for actions without finite nontrivial isotropy groups and with either fixed points or orbits with isotropy group isomorphic to SO(2) yields an equivariant classification for these cases. This classification is made numerically specific in terms of orbit invariants. A topological classification is obtained for actions on simply connected 4-manifolds. It is shown that such a manifold is an equivariant connected sum of copies of complex projective space CP2, — CP2 (reversed orientation), S2 x S2 and the other oriented S2 bundle over S2. The latter is diffeomorphic (but not always equivariantly diffeomorphic) to CP2 # —CP2. The connected sum decomposition is not unique. Topological actions on topological manifolds are shown to reduce to the smooth case. In an appendix certain results are extended to torus actions on orientable 4dimensional cohomology manifolds. Introduction. In this article we begin the study of actions of the two-dimensional torus group 50(2) x SO(2) on 4-manifolds. Our chief motivation for this study is that it enables one to construct, in a systematic way, a large number of nicely behaved 4-manifolds. These 4-manifolds can be described in terms of certain weighted 2-manifolds (orbit spaces with their orbit structures). To write down all possible actions of the torus on 4-manifolds is not too difficult but it is entirely a different matter to characterize topologically the 4-manifold from the orbit data. We may think of this study as two separate problems. By the equivariant problem we mean being able to write down enough data (orbit space, orbit types, etc.) so that when two sets of data arising from two actions (not necessarily on the same manifold) are examined, one can decide whether or not there is a homeomorphism between the two manifolds which is equivariant with respect to both actions. This problem is considerably easier than the topological classification problem. By topological classification we mean the topological identification and classification of the manifolds arising in terms of their data used for deciding the first problem. Received by the editors December 15, 1969. AMS 1968 subject classifications. Primary 5560, 5747.
Risk attribution of Campylobacter infection by age group using exposure modelling

SUMMARY Knowledge on the relative importance of alternative sources of human campylobacteriosis is important in order to implement effective disease prevention measures. The objective of this study was to assess the relative importance of three key exposure pathways (travelling abroad, poultry meat, pet contact) for different patient age groups in Switzerland. With a stochastic exposure model data on Campylobacter incidence for the years 2002–2007 were linked with data for the three exposure pathways and the results of a case-control study. Mean values for the population attributable fractions (PAF) over all age groups and years were 27% (95% CI 17–39) for poultry consumption, 27% (95% CI 22–32) for travelling abroad, 8% (95% CI 6–9) for pet contact and 39% (95% CI 25–50) for other risk factors. This model provided robust results when using data available for Switzerland, but the uncertainties remained high. The output of the model could be improved if more accurate input data are available to estimate the infection rate per exposure. In particular, the relatively high proportion of cases attributed to ‘other risk factors’ requires further attention.
Scanning electron microscopy of contactual interaction of sensitized lymphocytes with homologous target cells.

Scanning electron microscope (SEM) observations were conducted mainly on the in vitro interaction state between ]TC-II cells derived from Ehrlich ascites tumor and regional lymph node cells obtained from the mice I0 days after transplantation of Ehrlich ascites tumor. Cells cultured on the cover glass were fixed with glutaraldehyde, dehydrated with graded acetone solution, and covered with carbon and gold, were observed by SEM. The results may be briefly summarized as follows. On the surface of ]TC.II cells themselves are seen numerous fine microvilli projecting out regularly at right angle to the cell surface, which become attached to the glass, and there can be observed vacuoles in the cytoplasm. Such microvilli are lacking at the tip of the pseudopodial projection. The lymph node cells aggregated to ]TC-II cell are lymphocytes of small or intermediate size, and the pattern of aggregation varies: some lymphocytes effect an intimate contact with the surface of target cell by their cellular projections; the contact is achieved by interdigitation of microvilli between lymphocyte and target cell; b:>th cells form a bridge connection with a simple projection from each; or the two cells make a broad surface.to. surface contact. It is not possible to differentiate sensitized lymphocyte from nonsensitized one, their cell shape is spherical with rough surface and some cells show hole on the surface.
Cyclosporin Monitoring in Australasia: Survey of Laboratory Practices in 2000

Therapeutic drug monitoring of cyclosporin has been established as part of the routine clinical management of patients following organ transplantation for some 20 years. The current practices of laboratories in Australia and New Zealand have been surveyed for the year 2000 to update previous similar surveys in the light of considerable changes in CsA formulation (now exclusively Neoral® throughout Australasia), assay methods, and blood sampling strategies. The results, representing 93% of CsA laboratories in Australasia (n = 44), found that there was still a plethora of approaches adopted within each organ type for monitoring the established trough (C0) CsA concentration. There was a considerable uptake of 2-hour post-dose sampling (C2) monitoring practices, as demonstrated by assay requests to the responding laboratories, particularly in renal and liver transplantation (46% of centers). Most of these laboratories were also assaying C0 and/or to a much lesser extent, so-called limited sampling strategy AUC (lssAUC) samples at this time. The mFPIA (on TDx and AxSYM analyzers) were still strongly represented (54%) (relatively consistent with international data from the UKQAS proficiency testing scheme at this time) despite on-going concerns expressed in the literature about these methods. However, the Cedia assays had made considerable impact so soon after their introduction with 22% of the laboratories using Cedia or Cedia Plus (Microgenics or Roche Diagnostics; Sydney, Australia) methods. There were a wide variety of dilution protocols adopted in many centers for measuring samples above calibration ranges (such as C2 samples), and hence there was scope for improvement to fully validated techniques. Few centers (16%) made any attempt at interpretation of their results, many seeing their role as purely “measuring” (i.e., an analytical role), not “monitoring” (i.e., including assay and result interpretation). Despite many detailed attempts at providing international or national guidelines for CsA monitoring, etc., there is still considerable scope for improving the quality of the laboratory services offered in this complex as well as expensive area. Several respondents volunteered their support for further Australasian CsA monitoring consensus guidelines.
Anti-Mitochondrial Antibodies and Primary Biliary Cirrhosis in TGF-β Receptor II Dominant-Negative Mice1

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by lymphocytic infiltrates in portal tracts, selective destruction of biliary epithelial cells, and anti-mitochondrial Abs (AMAs). The elucidation of early events in the induction of tissue inflammation and autoimmunity in PBC has been hampered by the cryptic onset of the disease, the practical limitations in accessing the target tissue, and the lack of a suitable animal model. We demonstrate in this study that a mouse transgenic for directed expression of a dominant-negative form of TGF-β receptor type II (dnTGFβRII), under the direction of the CD4 promoter, mimics several key phenotypic features of human PBC, including spontaneous production of AMAs directed to the same mitochondrial autoantigens, namely PDC-E2, BCOADC-E2, and OGDC-E2. The murine AMAs also inhibit PDC-E2 activity. Moreover, there is lymphocytic liver infiltration with periportal inflammation analogous to the histological profile in human PBC. Additionally, the serum cytokine profile of affected mice mimics data in human PBC. The concomitant presence of these immunopathological features in the transgenic mice suggests that the TGF-βRII pathway is implicated in the pathogenesis of PBC. Finally, these data point away from initiation of autoimmunity by mechanisms such as molecular mimicry and more toward activation of an intrinsically self-reactive T cell repertoire in which necessary regulatory T cell influences are lacking.
Investigating the behavior of visually impaired users for multi‐session search tasks

Multi‐session search tasks are complex and span more than one web session. Such tasks are challenging because searchers must keep track of their search progress and the information they encounter across sessions. Multi‐session tasks can be cognitively taxing for visually impaired users because the lack of persistence of screen readers causes the load on working memory to be high. In this article, we first discuss the habitual behavior of visually impaired participants for multi‐session tasks when using popular search interfaces. We then present the evaluation of a search interface developed to support complex information seeking for visually impaired users. The user evaluation was structured in two sessions to simulate a multi‐session task. Thus, we discuss the strategies observed among participants to resume the search, to review previously encountered information, and to satisfy their evolved information need. We also compare the information‐seeking behavior across the two sessions and examine how the proposed interface supports participants for multi‐session tasks. Findings from this evaluation contribute to our understanding of the information‐seeking behavior of visually impaired users and have implications for the design of tools to support searchers to manage and make sense of information during multi‐session search tasks.
Disrupting Electronic Health Records Systems: The Next Generation

The health care system suffers from both inefficient and ineffective use of data. Data are suboptimally displayed to users, undernetworked, underutilized, and wasted. Errors, inefficiencies, and increased costs occur on the basis of unavailable data in a system that does not coordinate the exchange of information, or adequately support its use. Clinicians’ schedules are stretched to the limit and yet the system in which they work exerts little effort to streamline and support carefully engineered care processes. Information for decision-making is difficult to access in the context of hurried real-time workflows. This paper explores and addresses these issues to formulate an improved design for clinical workflow, information exchange, and decision making based on the use of electronic health records.