Miracle-dz/UniFAR-FTUs huggingface dataset:
Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys

ABSTRACT Differences in clinical outcome of simian immunodeficiency virus (SIV) infection in disease-resistant African sooty mangabeys (SM) and disease-susceptible Asian rhesus macaques (RM) prompted us to examine the role of regulatory T cells (Tregs) in these two animal models. Results from a cross-sectional study revealed maintenance of the frequency and absolute number of peripheral Tregs in chronically SIV-infected SM while a significant loss occurred in chronically SIV-infected RM compared to uninfected animals. A longitudinal study of experimentally SIV-infected animals revealed a transient increase in the frequency of Tregs from baseline values following acute infection in RM, but no change in the frequency of Tregs occurred in SM during this period. Further examination revealed a strong correlation between plasma viral load (VL) and the level of Tregs in SIV-infected RM but not SM. A correlation was also noted in SIV-infected RM that control VL spontaneously or in response to antiretroviral chemotherapy. In addition, immunofluorescent cell count assays showed that while Treg-depleted peripheral blood mononuclear cells from RM led to a significant enhancement of CD4+ and CD8+ T-cell responses to select pools of SIV peptides, there was no detectable T-cell response to the same pool of SIV peptides in Treg-depleted cells from SIV-infected SM. Our data collectively suggest that while Tregs do appear to play a role in the control of viremia and the magnitude of the SIV-specific immune response in RM, their role in disease resistance in SM remains unclear.
Strong Seasonality and Interannual Recurrence in Marine Myovirus Communities

ABSTRACT The temporal community dynamics and persistence of different viral types in the marine environment are still mostly obscure. Polymorphism of the major capsid protein gene, g23, was used to investigate the community composition dynamics of T4-like myoviruses in a North Atlantic fjord for a period of 2 years. A total of 160 unique operational taxonomic units (OTUs) were identified by terminal restriction fragment length polymorphism (TRFLP) of the gene g23. Three major community profiles were identified (winter-spring, summer, and autumn), which resulted in a clear seasonal succession pattern. These seasonal transitions were recurrent over the 2 years and significantly correlated with progression of seawater temperature, Synechococcus abundance, and turbidity. The appearance of the autumn viral communities was concomitant with the occurrence of prominent Synechococcus blooms. As a whole, we found a highly dynamic T4-like viral community with strong seasonality and recurrence patterns. These communities were unexpectedly dominated by a group of persistently abundant viruses.
Intakes of Selected Nutrients, Foods, and Phytochemicals and Prostate Cancer Risk in Western New York

Abstract: A number of epidemiological studies have suggested that diet may affect the etiology of prostate cancer, but few have investigated the impact of phytochemical intakes on this cancer. We conducted a case-control study of diet and prostate cancer in western New York involving 433 men with primary, histologically confirmed prostate cancer and 538 population-based controls, frequency matched to cases on age and county of residence. Diet was assessed with a detailed food-frequency questionnaire. We calculated daily intakes of nutrients and the phytochemicals β-sitosterol, campesterol, stigmasterol, total phytosterols, total lignan precursors, quercetin, and kaempferol based on published food composition data. Odds ratios (ORs) and 95% confidence intervals (CIs) describing the association of prostate cancer risk with selected nutrients, phytochemicals, and food groups were estimated with unconditional logistic regression. Compared with men in the lowest quartile of intake, reduced risks were observed for men in the highest quartile of intake of vitamin C (OR = 0.49; 95% CI = 0.33-0.74), β-carotene (OR = 0.53; 95% CI = 0.36-0.79), α-carotene (OR = 0.67; 95% CI = 0.47-0.97), lutein (OR = 0.55; 95% CI = 0.37-0.81), lycopene (OR = 0.62; 95% CI = 0.42-0.92), total lignan precursors (OR = 0.66; 95% CI = 0.47-0.94), quercetin (OR = 0.64; 95% CI = 0.44-0.92), and total vegetables (OR = 0.53; 95% CI = 0.36-0.79), but weak increased risks were observed for snacks and sweets (OR = 1.46; 95% CI = 0.95-2.23). Estimates associated with nutrients and phytochemicals were attenuated after adjustment for total vegetable intake. Nevertheless, our results support the hypothesis that a phytochemical-rich, plant-based diet is of importance in reducing risks of hormone-related neoplasms.
Twin study on ocular pressure following topically applied dexamethasone. II. Inheritance of variation in pressure response.

A twin study was undertaken to reevaluate a widely held monogenic hypothesis relating to the ocular hypertensive steroid response. In the present (part II) analysis, intrapair differences for steroid response among the monozygotic (MZ) and dizygotic (DZ) samples were compared. Responsiveness was treated as both a qualitative and quantitative trait. For the parameter change in pressure, significant differences were never observed between the MZ and DZ samples and heritability index was consistently low. For final pressure, differences between the twin classes showed a mixed pattern of significance; the heritability index was low- to mid-range. Such observations do not support a predominant role of inheritance. It seems evident that a theory of simple monogenic determination can be questioned on the basis of these new findings.
Evaluation of Three Pichia pastoris-Expressed Plasmodium falciparum Merozoite Proteins as a Combination Vaccine against Infection with Blood-Stage Parasites

ABSTRACT Because invasion of erythrocytes by Plasmodium falciparum merozoites involves multiple receptor-ligand interactions, it may be necessary to develop a multivalent malaria vaccine that is comprised of distinct parasite ligands. PfAMA-1, PfMSP1, and PfEBA-175 are merozoite proteins that play important roles in invasion. We have constructed a PfCP-2.9 chimeric protein consisting of PfAMA-1 and PfMSP1 and tested it for immunogenicity in animal models and humans. The F2 subdomain of PfEBA-175 (PfEBA-175II F2) was identified as the binding domain for glycophorin A on erythrocytes. In this study, we used the codon frequencies of the yeast Pichia pastoris to redesign and synthesize a gene encoding the F2 domain. We found that the codon-optimized gene was expressed at a high level in P. pastoris as a soluble protein with a yield of about 300 mg/liter. The expressed protein was able to bind normal erythrocytes but not those treated with neuraminidase or trypsin. Moreover, the protein was recognized by the sera of malaria patients and was highly immunogenic in mice, rabbits, and rhesus monkeys. Immunoglobulin G isolated from both immunized rabbits and monkeys inhibited in vitro parasite growth. Immunization of animals with a combination of PfEBA-175II F2 and PfCP-2.9 did not result in antigen (Ag) competition in animals. Moreover, antibodies to both PfEBA-175II F2 and PfCP-2.9, isolated from rabbits immunized with both constructs, inhibited parasite growth in vitro. The combination of high yield, functional folding, antibody inhibition, and lack of Ag competition provides support for inclusion of these merozoite proteins in a combination vaccine against infection with blood-stage parasites.
Outcome of HCV/HIV‐Coinfected Liver Transplant Recipients: A Prospective and Multicenter Cohort Study

Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%[95% CI, 54–80]) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.
The effect of sedation on gastric emptying of a liquid marker in ponies.

OBJECTIVE The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. EXPERIMENTAL DESIGN Prospective randomized experimental study. ANIMALS Six adult ponies, 135 to 275 kg. METHODS Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group. RESULTS Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.
Risk-adapted transplant strategies for high-risk Hodgkin lymphoma: are we there?

Purpose of review The treatment of high-risk classic Hodgkin lymphoma (cHL) patients remains challenging, especially after autologous stem cell transplant (ASCT) failure. Moreover, the outcome of chemorefractory patients is still poor. Recent findings The development of novel targeted therapies has changed the therapeutic options for high-risk patients. To improve outcome, treatment algorithms should integrate up-front, newly established prognostic markers. Tandem ASCT instead of single ASCT has been proposed as an option to improve outcome for high-risk patients. Availability of less toxic reduced intensity conditioning regimens and recent development in haploidentical transplantation have widened applicability and improved outcomes of allo-hematopoietic cell transplantation. Their exact role in cHL is still controversial and there is no consensus on the optimal transplantation strategy. In this context, results of tandem ASCT should also be compared with those of the autologous/reduced intensity conditioning-allo tandem approach. In this review, we discuss how transplantation strategies (auto and allo) can fit into the salvage treatment plan for patients with relapsed/refractory cHL, taking into account the new drugs available and integrating modern risk assessment. Summary We speculated that improvements could be achieved by transplanting patients in earlier phases of their disease, if necessary after ‘bridging’ using the new drugs, and we propose an algorithm integrating the different treatment options.
Analysis of the steric strain in the polypeptide backbone of protein molecules

The extent to which local strain is present in the polypeptide backbone of folded protein molecules has been examined. The occurrence of steric strain associated with nonproline cis peptide bonds and energetically unfavorable main chain dihedral angles can be identified reliably from the well ordered parts of high resolution, refined crystal structures. The analysis reveals that there are relatively few sterically strained features. Those that do occur are located overwhelmingly in regions concerned with function. We attribute this to the greater precision necessary for ligand binding and catalysis, compared with the requirements of satisfactory folding.
Gender bias in physicians' management of neck pain: a study of the answers in a Swedish national examination.

BACKGROUND Research has raised concerns about gender bias in medicine; that is, are women and men being treated differently because of gender stereotyped attitudes among physicians? We investigated gender differences in the diagnosis and management of neck pain as proposed in a written test. The design eliminated differences related to communication and patient behavior. METHODS In a national examination for Swedish interns, using modified essay questions, the examinees were allocated to suggest management of neck pain in either a male or a female bus driver with a tense family situation. The case description was identical with the exception of patient gender. The open answers were coded for analysis. Two hundred thirty-nine interns (41% women) participated. Chi-square-tests were used to measure differences in proportions, and t test was used to evaluate differences in means. RESULTS In certain areas, significant gender differences were detected. Proposals of nonspecific somatic diagnoses, psychosocial questions, drug prescriptions, and the expressed need of diagnostic support from a physiotherapist and an orthopedist were more common with females. Laboratory tests were requested more often in males. Both male and female physicians contributed to the gender differences. When assessing the impact of the patient-doctor relationship for health outcome, male physicians underlined the importance of patient compliance foremost in female patients, and female physicians did the opposite. CONCLUSIONS The results suggest that physicians' gendered expectations are involved in creating gender differences in medicine. The inclusion of gender theory and discussions about gender attitudes into medical school curricula is recommended to bring about awareness of the problem.
Noise investigation of an active non-foster matching network for small antennas

Matching networks with Non-Foster elements seem to be useful for the matching of small antennas. This paper presents the advantages and disadvantages of such a non-Foster matching network with active elements. Therefore a comparison with a conventional matching network regarding signal performance only and in addition regarding signal-to noise (SNR) performance for automotive application in the FM frequency range is made. In contrast to other publications a severe SNR disadvantage of the non-Foster network results.
XYY chromosome abnormality in sexual homicide perpetrators

In a retrospective investigation of the court reports about sexual homicide perpetrators chromosome analysis had been carried out in 13 of 166 (7.8%) men. Three men (1.8%) with XYY chromosome abnormality were found. This rate is much higher than that found in unselected samples of prisoners (0.7–0.9%) or in the general population (0.01%). The three men had shown prepubescent abnormalities, school problems, and had suffered from physical abuse. The chromosome analysis in all cases had been carried out in connection with the forensic psychiatric court report due to the sexual homicide. However, two men had earlier psychiatric referrals. All were diagnosed as sexual sadistic, showed a psychopathic syndrome or psychopathy according to the Psychopathy Checklist‐Revised [Hare RD, 1991, The Hare Psychopathy Checklist‐Revised, Toronto, Ontario, Canada: Multi‐Health Systems]. Two were multiple murderers. Especially forensic psychiatrists should be vigilant of the possibility of XYY chromosome abnormalities in sexual offenders. © 2006 Wiley‐Liss, Inc.
Fractional Flow Reserve Returns to Its Origins: Quantitative Cardiac Positron Emission Tomography.

After the initial publication in April 19931 of the theoretical model and animal validation of fractional flow reserve (FFR), the second article in March 19942 extended the concept to humans using quantitative cardiac positron emission tomography (PET). Now, >22 years later, FFR has revolutionized interventional cardiology by moving the yardstick from anatomy to physiology through a series of randomized trials3–5 and observational data.6 As such, the article by Lee et al7 in this issue of Circulation: Cardiovascular Imaging provides a timely opportunity to revisit the basic links between FFR and quantitative cardiac PET. See Article by Lee at al The key concept behind FFR relates stenotic hyperemic flow to hypothetical maximal hyperemic flow in the absence of a stenosis. Therefore, FFR quantifies one flow relative to another flow, providing a unitless fraction and purposely discarding information about the level of absolute flow. Conceptually, it has been appreciated since the beginning of FFR that under certain assumptions (single vessel disease, uniform myocardial vasodilation, and accounting for distal myocardial mass by expressing flow per unit tissue or cc/min/g), its numeric value equaled relative flow reserve (hyperemic flow in the stenotic artery divided by hyperemic flow in a normal artery). 2 The current article by Lee et al7 confirms and extends work by several other groups that PET-derived RFR and invasive FFR have an extremely linear relationship. Figure 1 visually summarizes the published literature of almost 450 lesions, demonstrating that FFR indeed provides a metric of relative flow reserve. Deviations from perfect linearity arise from measurement uncertainty (≈20% for PET-derived flow8 and 2% for invasive FFR9) plus violations of the assumptions listed earlier (most commonly the lack of a truly normal reference vessel because of multivessel or diffuse atherosclerosis). As confirmation, Lee et …
Time Dependent Release of Allergens from Some Xerophilic Fungi

Particles smaller than 10 ^m, e.g. diaspores of species of the genera Aspergillus and Wallemia, may penetrate into the human airways in spite ofthe presence of mucous membranes. Within 1 h the inhaled material is returned to the pharynx by the aid of these mucous membranes (12). Therefore, substances responsible for allergic reactions must be released within 1 h. Fast release of allergens from pollen has been reported before (4, 5, 6, 7). A number of investigators have tried in vain to isolate one single substance responsible for the allergic reaction from several kinds of materials (1, 3, 9, 10, 11). The opinion has formed that more than one allergic factor must be involved in allergy. According to Berrens (1) there are two mechanisms: 1) the specific reaction between antigen and antibody; 2) the non-specific reaction between lysine-sugar compounds and the human complement. In this short communication we will study the effect of extraction time on recovery ofthe two types of allergic factors and hypothesise on their relevance to the allergic patient.
An overview of the evolution of enterovirus 71 and its clinical and public health significance.

Since its discovery in 1969, enterovirus 71 (EV71) has been recognised as a frequent cause of epidemics of hand-foot-and-mouth disease (HFMD) associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary oedema and high case-fatality rates. The emergence of large-scale epidemic activity in the Asia-Pacific region has been associated with the circulation of three genetic lineages that appear to be undergoing rapid evolutionary change. Two of these lineages (B3 and B4) have not been described previously and appear to have arisen from an endemic focus in equatorial Asia, which has served as a source of virus for HFMD epidemics in Malaysia, Singapore and Australia. The third lineage (C2) has previously been identified [Brown, B.A. et al. (1999) J. Virol. 73, 9969-9975] and was primarily responsible for the large HFMD epidemic in Taiwan during 1998. As EV71 appears not to be susceptible to newly developed antiviral agents and a vaccine is not currently available, control of EV71 epidemics through high-level surveillance and public health intervention needs to be maintained and extended throughout the Asia-Pacific region. Future research should focus on (1) understanding the molecular genetics of EV71 virulence, (2) identification of the receptor(s) for EV71, (3) development of antiviral agents to ameliorate the severity of neurological disease and (4) vaccine development to control epidemics. Following the successful experience of the poliomyelitis control programme, it may be possible to control EV71 epidemics if an effective live-attenuated vaccine is developed.
Surface modified poly(amido)amine dendrimers as diverse nanomolecules for biomedical applications

The unique properties of poly(amido)amine dendrimers such as nano size, multifunctional surface, ability to encapsulate and bind the guest molecules, efficient membrane transport and shelf-life stability have made them a promising carrier in drug delivery. The two key applications of dendrimers include increasing the solubility and sustained release of molecules, and drug targeting by grafting the cell-specific ligands on the surface. Despite their potential in drug delivery, inherent cytotoxicity, reticuloendothelial system uptake and hemolysis limit their use in clinical applications. Research groups have been working on surface modification methods to mitigate these problems. Herein we present a brief discussion on current surface modification approaches to: i) increase targeting efficiency; ii) increase the cellular permeability for enhanced absorption; iii) increase gene transfection efficiency; and iv) decrease the toxicity of the dendrimers, with a few classic examples. As the knowledge of relationship between the dendrimer surface chemistry and its mode of interactions with cell membrane is developed, so do the modifications of dendrimer structure to render them nontoxic, biocompatible, biodegradable and improve their pharmacodynamic and pharmacokinetic properties. Development of multifunctional dendrimers with each functional unit imparting a distinct characteristic feature such as target cell recognition, enhanced cellular transport, reduction in reticuloendothelial system uptake and stability in in vivo environment holds a great potential for future biomedical applications.