Miracle-dz/UniFAR-FTUs huggingface dataset:
The alphaviruses: gene expression, replication, and evolution

The alphaviruses are a genus of 26 enveloped viruses that cause disease in humans and domestic animals. Mosquitoes or other hematophagous arthropods serve as vectors for these viruses. The complete sequences of the +/- 11.7-kb plus-strand RNA genomes of eight alphaviruses have been determined, and partial sequences are known for several others; this has made possible evolutionary comparisons between different alphaviruses as well as comparisons of this group of viruses with other animal and plant viruses. Full-length cDNA clones from which infectious RNA can be recovered have been constructed for four alphaviruses; these clones have facilitated many molecular genetic studies as well as the development of these viruses as expression vectors. From these and studies involving biochemical approaches, many details of the replication cycle of the alphaviruses are known. The interactions of the viruses with host cells and host organisms have been exclusively studied, and the molecular basis of virulence and recovery from viral infection have been addressed in a large number of recent papers. The structure of the viruses has been determined to about 2.5 nm, making them the best-characterized enveloped virus to date. Because of the wealth of data that has appeared, these viruses represent a well-characterized system that tell us much about the evolution of RNA viruses, their replication, and their interactions with their hosts. This review summarizes our current knowledge of this group of viruses.
Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients

In 29 antiretroviral-naive HIV-2-infected patients starting lopinavir/ritonavir-containing regimen, the median CD4 cell count change from baseline (142 cells/μl) was +71 cells/μl at week 24 and +132 cells/μl at week 96. Seventeen (59%) patients had a CD4 cell count increase of at least 50 cells/μl and undetectable HIV-2 RNA at week 24 and were considered as responders to treatment. This sustained elevation of CD4 cell count in the first 2 years of combination antiretroviral therapy shows the potential for lopinavir/ritonavir regimens as first-line therapy in HIV-2 infection.
Suppression of intravascular signal on fat-saturated contrast-enhanced thoracic MR arteriograms.

PURPOSE To assess the prevalence of artifactual signal intensity loss within the aortic arch and proximal branch vessels on fat-saturated contrast material-enhanced magnetic resonance (MR) arteriograms of the thoracic aorta and to hypothesize about the cause of the loss of signal intensity. MATERIALS AND METHODS Between January and June 1998, 105 consecutive MR arteriograms of the thoracic aorta were acquired in 103 patients at 1.5 T. Imaging included an arterial phase three-dimensional (3D) fat-saturated contrast-enhanced gradient-echo (GRE) sequence followed by a delayed two-dimensional (2D) transverse fat-saturated GRE sequence. All MR images were reviewed by two radiologists who were blinded to patient history and results of imaging studies and who evaluated the images for the presence of intraluminal loss of signal intensity in the aortic arch and the proximal branch vessels. RESULTS Intravascular loss of signal intensity was present in at least one vessel on 23 of the 105 arterial phase 3D studies. Seventy-one of 91 left subclavian arterial segments had loss of signal intensity on the delayed 2D studies. CONCLUSION Intravascular signal intensity loss can be present on contrast-enhanced fat-saturated images of the aortic arch and proximal branch vessels, particularly the left subclavian artery. This phenomenon, which is to the authors' knowledge previously unreported and which is hypothesized to result from undesired water saturation, should not be misinterpreted as stenotic or occlusive vascular disease.
Antimicrobial Properties of a Novel Silver-Silica Nanocomposite Material

ABSTRACT Nanotechnology enables development and production of novel silver-based composite materials. We used in vitro tests to demonstrate the antimicrobial activity of a silver-silica nanocomposite compared to the activities of conventional materials, such as silver nitrate and silver zeolite. A silver-silica-containing polystyrene material was manufactured and shown to possess strong antimicrobial properties.
Processing of Recombinant Listeria monocytogenes Proteins for MHC Class I Presentation Follows a Dedicated, High-Efficiency Pathway

CD8+ T lymphocytes recognize short peptides of ∼8–10 aa bound to MHC class I molecules (pMHC) on the surface of APCs. These peptides can be generated from either endogenous proteins synthesized by the biosynthetic machinery of the presenting cell or from exogenously sourced proteins. Because much of the research characterizing the MHC class I processing pathway has focused on endogenously synthesized proteins, it is not known whether differences exist in the processing pathway followed by endogenously synthesized versus exogenously sourced proteins. To highlight potential differences in the processing of endogenous versus exogenous proteins, we developed a model system to measure the efficiency of pMHC generation from nearly identical recombinant proteins expressed from vaccinia virus and Listeria monocytogenes. In these experiments, we uncovered a striking difference in the way recombinant Listeria Ags are processed and presented when compared with endogenously synthesized viral proteins. Specifically, we find that pMHC production from secreted Listeria proteins occurs at the same rate, independent of the cellular half-life of the protein from which it is derived, whereas the rate of pMHC production from endogenously synthesized viral proteins is absolutely dependent on its protein half-life. Accordingly, our data demonstrate the existence of a distinct and highly efficient MHC class I presentation pathway used for the processing of at least some exogenously synthesized proteins.
Translational and emerging clinical applications of metabolomics in cardiovascular disease diagnosis and treatment

Numerous molecular screening strategies have recently been developed to measure the chemical diversity of a population’s biofluids with the ultimate aim to provide clinicians, medical scientists and epidemiologists with a clearer picture of the presence and severity of cardiovascular disease; prognosis; and response to treatment. Current cardiology practice integrates clinical history and examination with state-of-the-art imaging, invasive measures, and electrical interrogation. Biomarkers in common clinical use are relatively limited to troponin and brain natriuretic peptide, dependent on damage to heart muscle, or myocyte ‘stretch’ respectively. Although they have been recently applied to risk stratification in asymptomatic individuals at higher risk, the development of markers capable of detecting earlier phases of disease development would facilitate targeted strategies to prevent pathological complications in the general community. Metabolomics is the systematic study of small molecules in biological fluids. Profiling strategies aim to comprehensively measure and quantify such biomarkers in a fast, cost-effective and clinically informative manner. Techniques tend to be applied in an unbiased fashion, with advanced statistical methods allowing for identification of signature profiles in particular cohorts. In this manner, metabolomics has the potential to identify new pathophysiological pathways, and thus therapeutic targets, as well as assist in improved risk-stratification and personalized cardiovascular medicine. The latter has great potential in the primary and secondary cardiovascular disease prevention settings, integrating known and as yet unidentified host and environmental factors. The current review discusses applications of metabolomic techniques relevant to both the research and the clinical cardiologist.
Socioeconomic Status Moderates the Association Between John Henryism and NEO PI-R Personality Domains

Objective: To investigate associations between John Henryism (JH) and NEO Personality Inventory-Revised (PI-R) personality domains. JH—a strong behavioral predisposition to engage in high-effort coping with difficult psychosocial and economic stressors—has been associated with poor health, particularly among persons in lower socioeconomic (SES) groups. Unfavorable personality profiles have also been frequently linked to poor health; however, no studies have yet examined what global personality traits characterize JH. Methods: Hypotheses were examined, using data from a sample of 233 community volunteers (mean age, 33 years; 61% black and 39% white) recruited specifically to represent the full range of the SES gradient. Personality (NEO PI-R) and active coping (12-item JH scale) measures and covariates were derived from baseline interviews. Results: In a multiple regression analysis, independent of SES, JH was positively associated with Conscientiousness (C) (p < .001) and Extraversion (E) (p < .001), whereas the combination of low JH and high SES was associated with Neuroticism (N) (p = .02) When examining associations between JH and combinations of NEO PI-R domains called “styles,” high JH was most strongly associated with a high E/high C “Go-Getters” style of activity, whereas low JH was associated with the low E/high Openness (O) “Introspectors” style. In facet level data, the most robust associations with JH were found for five C and five E facets. Conclusions: High JH was associated with higher scores on C and E, but the combination of low JH and high SES was associated with higher scores on N. SES = socioeconomic status; JH = John Henryism; N = Neuroticism; C = Conscientiousness; E = Extraversion; A = Agreeableness; O = Openness.
The emerging role of exosome and microvesicle‐ (EMV‐) based cancer therapeutics and immunotherapy

There is an urgent need to develop new combination therapies beyond existing surgery, radio‐ and chemo‐therapy, perhaps initially combining chemotherapy with the targeting specificities of immunotherapy. For this, strategies to limit inflammation and immunosuppression and evasion in the tumour microenvironment are also needed. To devise effective new immunotherapies we must first understand tumour immunology, including the roles of T cells, macrophages, myeloid suppressor cells and of exosomes and microvesicles (EMVs) in promoting angiogenesis, tumour growth, drug resistance and metastasis. One promising cancer immunotherapy discussed uses cationic liposomes carrying tumour RNA (RNA‐lipoplexes) to provoke a strong anti‐viral‐like (cytotoxic CD8+) anti‐tumour immune response. Mesenchymal stem cell‐derived EMVs, with their capacity to migrate towards inflammatory areas including solid tumours, have also been used. As tumour EMVs clearly exacerbate the tumour microenvironment, another therapy option could involve EMV removal. Affinity‐based methods to deplete EMVs, including an immunodepletion, antibody‐based affinity substrate, are therefore considered. Finally EMV and exosome‐mimetic nanovesicles (NVs) delivery of siRNA or chemotherapeutic drugs that target tumours using peptide ligands for cognate receptors on the tumour cells are discussed. We also touch upon the reversal of drug efflux in EMVs from cancer cells which can sensitize cells to chemotherapy. The use of immunotherapy in combination with the advent of EMVs provides potent therapies to various cancers.
Evaluation of the Anti-Leishmania Major Activity of Satureja Bakhtiarica Essential Oil in Vitro

Leishmaniasis is a painless chronic skin disease that is caused by the protozoan parasite Leishmania. Due to the importance of this disease and the side effects of chemical drugs, use of drugs of plant origin to treat Leishmaniasis is very important. In the present study, the chemical composition and the anti-Leishmania major activity of the essential oils obtained from Satureja bakhtiarica were evaluated in vitro. The oils were extracted using a Clevenger apparatus and then the chemical composition was analyzed by GC-MS. Promastigotes of L. major were cultured in both N.N. N and RPMI1640 media. GC-MS analysis showed 13 compounds, in which the major components were the phenolic (37.4%) compounds, thymol (22.6%) and p-cymene (19.3%). The essential oil of S. bakhtiarica showed higher activity against L. major than the standard anti-Leishmania drug, glucantime,. Perhaps because of the high concentration of phenolic compounds in the essential oil, all the parasites were killed after 24 hours. The essential oil from S. bakhtiarica is a potential plant drug against leishmaniasis. Further studies are necessary to evaluate this oil in animal models (in vivo) for future drug applications.
The ‘Act When Mild’ (AwM) Study: A Step Forward in Our Understanding of Early Treatment in Acute Migraine

An important issue in the management of migraine is the advice given to patients as to when to take their treatment in the course of the attack. While it seems common sense almost to take treatment early in the attack, the evidence base for that advice is not as robust as could be expected. The ‘Act when Mild’ (AwM) Study was a randomized, four-arm, multicentre, multinational, double-blind, placebo-controlled trial of almotriptan (12.5 mg) to compare outcomes after administration of treatment when pain intensity was mild and within 1 h of headache onset (mild/early) with outcomes when pain had become moderate or severe. Of 491 migraineurs enrolled, 403 were evaluable with an intention-to-treat population (ITT) of 404. At the primary end-point, 2 h pain free, on the ITT analysis 49% of patients in the almotriptan 12.5 mg treat early/mild group and 40% in the treat moderate/severe group had responded (P = 0.21). Of these patients, 43 did not take medication according to their randomly allocated baseline pain intensity (mild or moderate/severe) and were subsequently reassigned, prior to study unblinding, to the appropriate group (AwM population) for re-analysis of the primary outcome measure: 2-h pain-free rates. In the almotriptan arms, 53% of the mild/early group and 37.5% of the moderate/severe group were pain free at 2 h (P = 0.02; AwM population). The corresponding proportions in the placebo groups were 24.7% and 17.5% (significantly lower than the respective almotriptan arms; P ≤ 0.01). Considering the ITT population, secondary end-points were also significantly in favour of treatment with almotriptan in the mild/early vs. the moderate/severe stage, including: sustained pain-free, 45.6% vs. 30.5% (P = 0.02); headache recurrence at 24 h, 6% vs. 24% (P = 0.0124). Adverse events were reported in < 5% of patients, with no significant differences between almotriptan and placebo and no serious events in any group. Treatment with almotriptan while migraine pain is still mild and within 1 h of onset provides statistically significant and clinically relevant enhancements in efficacy compared with waiting until pain has reached higher severity levels.
The emergence of segmental accuracy in young cochlear implant recipients

Abstract In the first steps toward intelligible speech, children must match sounds they can produce with salient word targets from their environment. Differences in auditory history between normal-hearing children (NH) and children receiving cochlear implants (CI) before the age of 24 months afford examination of the production system and auditory perceptual effects on the emergence of early segmental accuracy. Consonant and vowel inventories, accuracy and error patterns during the single-word period were examined in four NH and four CI children. NH and CI groups differed significantly on consonant accuracy, shifting from omissions to correct productions. Vowel productions improved from partially correct to correct. Both groups improved over time and showed similar patterns for segmental accuracy. Results suggest resilience of the production system to differences in auditory history. Copyright © 2008 John Wiley & Sons, Ltd.
Role of non‐capsulated Haemophilus influenzae as a respiratory pathogen in children

During a 12‐month surveillance period from 1981‐1982, non‐capsulated Haemophilus influenzae was detected in nasopharyngeal aspirates from 64 (14%) of the 449 children hospitalized for middle or lower respiratory infection. An antibody response to H. influenzae was indicated in 15(23%) of the 64 patients with H. influenzae present in nasopharyngeal aspirate and in 10(3%) of the 385 patients with a negative finding. Thus, serological evidence of H. influenzae infection was demonstrated in 25(6%) of all the 449 children with respiratory infection. Of 13 patients with cultures positive for H. influenzae acute otitis media, an antibody response was seen in only 4(30%) patients. H. influenzae infection was associated with infections caused by other microbes in 20 children (80%), with viral infections in 60% and with pneumococcal infections in 24% of cases. An infection focus was present in 15(79%) of the 25 patients with H. influenzae infection; pneumonia was present in 10 cases and acute otitis media in 9 cases. Non‐specific laboratory evidence of bacterial infection was seen in 11 patients (58%); C‐reactive protein was increased in 7 and erythrocyte sedimentation rate in 9 patients. It is concluded that non‐capsulated H. influenzae is a genuine respiratory pathogen in children. H. influenzae infections appear to be secondary to preceding viral or other bacterial infections in children who are carriers of this strain.
Health Disparities

The existence of significant health disparities beyond those associated with race/ethnicity, poverty, and lack of health care has drawn the attention of researchers to the “challenge of the gradient. ” Studies progressed from describing cross-sectional associations between disease risk and a single aspect of social disadvantage to identifying mechanisms by which these associations occur, encompassed objective and subjective measures of social status and stress processes, and used multilevel, dynamic models over the life course. The next stage is developing effective interventions targeting both the bases of disadvantage and the mediating pathways to reduce persistent disparities.
Should the 'bleach microscopy method' be recommended for improved case detection of tuberculosis? Literature review and key person analysis.

SETTING It has been proposed that the sensitivity of direct sputum smear microscopy can be improved if sputum is liquefied with sodium hypochlorite (NaOCl or household bleach), and concentrated by centrifugation before acid-fast staining. OBJECTIVE To summarise the results of the studies of the bleach method for improved sensitivity of sputum microscopy and to describe the opinions and knowledge of key persons in National Tuberculosis Control Programmes (NTPs) about this method. DESIGN We searched Medline, EMBASE and Web of Science for studies comparing the bleach method to direct sputum smear microscopy in low- or middle-income countries. Each study was assessed regarding methodology and field applicability. We also sent out questionnaires concerning the bleach method to key persons in NTPs in 85 countries. RESULTS In 15 of the 19 studies identified there was a statistically significant improvement in the proportion of positive tests or sensitivity ranging from 7-253%. The majority (73%) of the key persons had heard of the bleach method. Forty-four per cent thought it could improve case detection in their countries, while 49% did not know; 93% of them would promote the bleach method; the most common reasons for doing so would be recommendations from the WHO or the IUATLD, or favourable studies performed in their own country. The bleach method was used routinely in only three countries. CONCLUSION There is enough evidence to recommend the evaluation and introduction of the bleach method in most settings where mycobacterial culture is not performed routinely.
Estimate of bottom and surface stress during a spring-neap tide cycle by dynamical assimilation of tide gauge observations in the Chesapeake Bay

Dynamical assimilation of surface elevation from tide gauges is investigated to estimate the bottom drag coefficient and surface stress as a first step in improving modeled tidal and wind-driven circulation in the Chesapeake Bay. A two-dimensional shallow water model and an adjoint variational method with a limited memory quasi-Newton optimization algorithm are used to achieve this goal. Assimilation of tide gauge observations from 10 permanent stations in the Bay and use of a two-dimensional model adequately estimate the bottom drag coefficient, wind stress, and surface elevation at the Bay mouth. Subsequent use of these estimates in the circulation model considerably improves the modeled surface elevation in the entire Bay. Assimilation of predicted tidal elevations yields a drag coefficient, defined in the hydraulic way, varying between 2.5 x 10 -4 and 3.1 x 10 -3 . The bottom drag coefficient displays a periodicity corresponding to the spring-neap tide cycle with a maximum value during neap tide and a minimum value during spring tide. From assimilation of actual tide gauge observations, it is found that the fortnightly modulation is altered during frontal passage. Furthermore, the response of the sea surface to the wind forcing is found to be more important in the lower Bay than in the upper Bay, where the barometric pressure effect seems to be more important.
Femoral trochlear dysplasia: MR findings.

PURPOSE To establish quantitative and qualitative magnetic resonance (MR) criteria for the diagnosis of trochlear dysplasia. MATERIALS AND METHODS MR images were analyzed in 16 consecutive patients with and 23 without trochlear dysplasia. The standard of reference was a true lateral radiograph of the knee. Quantitative and qualitative MR criteria were assessed. RESULTS In patients with trochlear dysplasia, the trochlear groove was significantly less deep than that in control subjects. The most accurate measurement was 3 cm above the femorotibial joint space (P: <.001), where a trochlear depth of 3 mm or less had a sensitivity of 100% and a specificity of 96%. The ventral trochlear prominence between the supratrochlear femoral cortex and the most ventral point of the trochlear floor (midsagittal section) was always larger than 6.9 mm in dysplastic trochleae. A facet ratio of less than 2:5 (medial to lateral) 3 cm above joint space level had a sensitivity of 100% and a specificity of 96%. A nipplelike anterior prominence at the superior end of the femoral trochlea on midsagittal images was a specific (91%) qualitative criterion. CONCLUSION Dysplasia of the femoral trochlea can be diagnosed reliably by using quantitative or qualitative criteria on midsagittal or transverse MR images obtained 3 cm above the femorotibial joint space.
Rosmarinic acid administration attenuates diabetes‐induced vascular dysfunction of the rat aorta

Oxidative stress as well as inflammation processes are engaged in diabetic vascular complications. Rosmarinic acid, a natural phenol antioxidant carboxylic acid, was found to have multiple biological activity, including anti‐inflammatory and antitumour effects, which are a consequence of its inhibition of the inflammatory processes and of reactive oxygen species scavenging. The aim of this work was to study effects of rosmarinic acid administration on vascular impairment induced by experimental diabetes in rats.
Parental decisions following prenatal diagnosis of sex chromosome aneuploidy in Hong Kong

According to the published work, pregnancy termination rates due to prenatal diagnosis of fetal sex chromosome aneuploidies (SCA) vary widely. Some potentially modifiable and non‐modifiable factors have been reported to be associated with parental decision. This study aimed to evaluate the rate of pregnancy termination for fetal SCA and the factors influencing parents' decisions in Hong Kong.