Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitating the Magnitude of the Lymphocytic Choriomeningitis Virus-Specific CD8 T-Cell Response: It Is Even Bigger than We Thought

ABSTRACT Measuring the magnitudes and specificities of antiviral CD8 T-cell responses is critical for understanding the dynamics and regulation of adaptive immunity. Despite many excellent studies, the accurate measurement of the total CD8 T-cell response directed against a particular infection has been hampered by an incomplete knowledge of all CD8 T-cell epitopes and also by potential contributions of bystander expansion among CD8 T cells of irrelevant specificities. Here, we use several techniques to provide a more complete accounting of the CD8 T-cell response generated upon infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV). Eight days following infection, we found that 85 to 95% of CD8 T cells exhibit an effector phenotype as indicated by granzyme B, 1B11, CD62L, CD11a, and CD127 expression. We demonstrate that CD8 T-cell expansion is due to cells that divide >7 times, whereas heterologous viral infections only elicited <3 divisions among bystander memory CD8 T cells. Furthermore, we found that approximately 80% of CD8 T cells in spleen were specific for ten different LCMV-derived epitopes at the peak of primary infection. These data suggest that following a single LCMV infection, effector CD8 T cells divide ≥15 times and account for at least 80%, and possibly as much as 95%, of the CD8 T-cell pool. Moreover, the response targeted a very broad array of peptide major histocompatibility complexes (MHCs), even though we examined epitopes derived from only two of the four proteins encoded by the LCMV genome and C57BL/6 mice only have two MHC class I alleles. These data illustrate the potential enormity, specificity, and breadth of CD8 T-cell responses to viral infection and demonstrate that bystander activation does not contribute to CD8 T-cell expansion.
Expression of Prototype Foamy Virus Pol as a Gag-Pol Fusion Protein Does Not Change the Timing of Reverse Transcription

ABSTRACT Foamy viruses are retroviruses whose Pol protein is synthesized without Gag from a spliced mRNA. Unlike orthoretroviruses, reverse transcription occurs during viral assembly, leading to DNA-containing virions. When prototype foamy virus Pol is expressed as an orthoretroviral-like Gag-Pol fusion protein, reverse transcription also occurs late in viral replication, as measured by the timing of reverse transcriptase sensitivity to the inhibitor 3′-azido-3′deoxythymidine (AZT). Thus, timing of reverse transcription is intrinsic to Pol itself.
Outdoor allergenic fungal spores: comparison between an urban and a rural area in northern Portugal.

BACKGROUND The frequency and concentration of many airborne fungal spores associated with respiratory allergy symptoms are influenced by geographical and climatic characteristics. OBJECTIVE The aim of this work was to monitor the distribution of 11 potentially allergenic fungal spore types in 2 regions with different urbanization levels in Northern Portugal: Porto (urban area) and Amares (rural area). METHODS Airborne fungal spore levels were monitored from 2005 to 2007 using Hirst-type spore traps. The Spearman correlation test was used to analyze the influence of meteorological factors (temperature, relative humidity, and rainfall) on spore concentration. Meteorological data from both areas were compared using the t test, and spore concentrations were compared using the sign test. RESULTS In both areas, Cladosporium, Agaricus, Aspergillus/Penincillium, Altemaria, Coprinus, and rusts were the most abundant fungal types observed. Most of the analyzed spore types presented maximum values during the summer months, with the exception of Polythrincium, Stemphylium, and Torula, which reached a peak earlier in the year, whereas Aspergillus/Penicillium and Botrytis showed a wider distribution. Temperature had a positive effect on most spore concentrations, and relative humidity and rainfall negatively influenced concentrations ofAlternaia, Cladosporium, Epicoccum, and Torula. CONCLUSIONS The concentration of all selected spore types was higher in the rural than in the urban area, with higher values registe summer and autumn and lower values found during winter and spring. rainfall, influence airborne concentrations of major allergenic fungal spores.
Siderophore production by Pseudomonas pseudomallei

Eighty-four strains of Pseudomonas pseudomallei isolated from patients with melioidosis were examined for siderophore production. All the strains were shown to produce siderophore both on chrome azurol S agar plates and in liquid medium under iron-deficient conditions. Chemical assays indicated that the siderophore belongs to the hydroxamate class. Addition of iron to the culture medium resulted in increased culture growth with markedly decreased yield of siderophore. Siderophore produced by strain U7 was purified by gel filtration chromatography, and the molecular weight was estimated to be 1,000. When this partially purified siderophore was added to culture medium, it promoted iron uptake by P. pseudomallei in the presence of EDTA and enhanced growth of the organism in the presence of transferrin. We have given this siderophore the trivial name malleobactin.
Analyzing epigenetic control of galectin expression indicates silencing of galectin‐12 by promoter methylation in colorectal cancer

Galectins, a class of lectins with specificity for ß‐galactoside containing glycoconjugates, modulate several cellular processes that are involved in the control of normal cell growth, differentiation, cell‐cell, and cell matrix interactions. Pathological alterations of the galectin expression pattern have been implicated in the development and progression of cancer. We therefore analyzed epigenetic mechanisms for control of galectin expression in 9 colorectal cancer (CRC) cell lines. Our data demonstrate that expression of galectins‐1, −2, −7, −8, and −9 can be regulated by histone acetylation in CRC cell lines. In addition, the same set of galectins was also found to be modulated by DNA methylation. Of particular note, galectin‐12 is silenced in all tested CRC cell lines but known to be re‐expressed upon butyrate‐induced differentiation and present in normal colonic mucosa. Loss of galectin‐12 expression in undifferentiated CRC cells is associated with promoter hypermethylation and for the first time we provide detailed methylation analysis of the promoter region. In CRC tumor tissue, galectin‐12 expression was downregulated in 66% of CRC tissue specimens as compared to adjacent normal tissue hinting to a possible tumor‐suppressing function in CRC. © 2017 IUBMB Life, 69(12):962–970, 2017
Vancomycin Intermittent Dosing versus Continuous Infusion for Treatment of Ventilator-associated Pneumonia in Trauma Patients

Current guidelines for the empiric treatment of ventilator-associated pneumonia (VAP) recommend that vancomycin is dosed 15 mg/kg and administered twice daily for a target trough level of 15 to 20 mg/mL. This study compared conventional intermittent vancomycin infusion (IVI) with continuous vancomycin infusion (CVI). Our prospective, randomized study compared CVI with IVI in trauma patients with suspected VAP. The primary outcome measure was a serum vancomycin level within the target level 48 hours after initiation of therapy. Treatment groups were compared using standard statistical methods. The study included 73 patients, 36 IVI and 37 CVI. Eighteen patients were withdrawn from the study as a result of discontinuation of the drug before 48 hours or failure to draw levels at the appropriate time, resulting in 27 IVI and 28 CVI study patients. There were no differences between treatment groups in gender (P = 0.97), Injury Severity Score (P = 0.70), total body weight (P = 0.36), or age (P = 0.81). The mean serum vancomycin level for the IVI group was 8.9 ± 3.9 mg/mL, and the CVI level was 19.8 ± 6.13 mg/mL (P < 0.0001). Two patients in the IVI group (7.4%) were in the therapeutic range compared with 16 (57.1%) in the CVI group (P < 0.0001). Six patients in the CVI group (21.4%) and none of the IVI patients had supratherapeutic levels. Four patients developed renal insufficiency, three IVI (11.1%) and one CVI (3.6%) (P = 0.36). The current American Trauma Society dosing recommendations for vancomycin for presumptive VAP treatment are inadequate. Continuous vancomycin infusion should be adopted as the standard dosing strategy.
A genomic region encompassing a cluster of olfactory receptor genes and a myosin light chain kinase (MYLK) gene is duplicated on human chromosome regions 3q13-q21 and 3p13.

The olfactory receptor (OR) multigene family is widely distributed in the human genome. We characterize here a new cluster of four OR genes (HGMW-approved symbols OR7E20P, OR7E6P, OR7E21P, and OR7E22P) on human chromosome 3p13 that is contained in an approximately 250-kb region. This region has been physically mapped, and a 106-kb portion containing the OR genes has been sequenced. All the OR sequences are disrupted by frameshifts and stop codons and appear to have arisen through local duplications. A myosin light chain kinase pseudogene (HGMW-approved symbol MYLKP) lies at one end of the OR gene cluster. Sequences spanning the entire region are also present at 3q13-q21, the site of the functional MYLK gene. This region duplicated locally before the divergence of primates, and the two paralogous copies were later separated to sites on either side of the centromere. This study increases our understanding of the evolution of the human genome. The 3p13 cluster is the first example of a tandem array of OR pseudogenes, and duplications of such clusters may account for the accumulation of a large number of pseudogenes in the human genome.
Transfusion of platelet concentrates – clinical evaluation of two preparations

Abstract: The aim of this study was to compare the clinical effect of transfusion of platelet concentrates (PC) prepared from pooled buffy coats (BC) and PCs collected from a single donor (SD) by an apheresis technique. The influence of storage time and various clinical conditions was also studied. Thirty‐two patients suffering from haematological malignancies were given a total of 326 platelet concentrates; 180 BC‐PCs and 146 SD‐PCs, median 7 transfusions per patient. BC‐PCs contained 312±52×109 and SD‐PCs 383 ± 133 × 109 platelets/unit (mean ± SD). The mean storage time of BC‐PC was 3 d and that of SD‐PC 1 d. The mean platelet count of the patients before transfusion was 11 ± 8 ×109/L. Regression analysis showed a significant decrease of the post‐transfusion platelet corrected count increment (CCI) during storage of PCs for 1–5 d (BC‐PC: p <0.01; SD‐PC: p <0.05). There was no difference in platelet increment between BC‐PC and SD‐PC. Human leukocyte antigen (HLA) alloimmunization was the major cause of clinical refractoriness to random donor platelet transfusions but splenomegaly also caused low CCI values.
Cardiac retransplantation for graft vasculopathy in children: should we continue to do it?

BACKGROUND Cardiac transplantation (CTx) has been established as an effective therapy for a variety of inoperable cardiac conditions in infants and children. However, graft vasculopathy (GV) has emerged as the main limiting factor to long-term survival of CTx recipients. The only treatment of severe GV is cardiac retransplantation (re-Tx). Controversy exists regarding the use of scarce donor organs for cardiac re-Tx. OBJECTIVE To compare the outcome of cardiac re-Tx for GV with that of primary CTx in children. DESIGN A 12-year retrospective cohort review. SETTING A university-affiliated children's hospital. PATIENTS All infants and children who underwent CTx (group 1, n = 322) had complete follow-up of 1389.7 patient-years. Graft vasculopathy was confirmed in 32 recipients (1.1-8.2 years after undergoing CTx). Thirteen patients died suddenly, 3 died waiting for cardiac re-Tx (1-17 days after relisting), 4 are pending cardiac re-Tx, and 12 (group 2) underwent cardiac re-Tx. INTERVENTION Cardiac re-Tx at a mean (+/- SD) interval from the first CTx of 6.3 +/- 1.8 years (range, 2.2-9.4 years). Two patients required additional aortic arch aneurysm repair with cardiac re-Tx. RESULTS When group 1 was compared with group 2, there was no significant difference in operative mortality (9.0% vs 8.3%; P = .9), rejection rate (0.98 vs 0.86; P = .1), and hospital stay (23.0 +/- 18.8 days vs 20.5 +/- 11.6 days; P = .65). Actuarial survival for groups 1 and 2 at 1 and 4 years was 84.3% vs 83.3% (P = .59) and 74.4% vs 83.3% (P = .85), respectively. CONCLUSIONS The surgical outcome and intermediate survival of cardiac re-Tx for GV and primary CTx are similar. Children with severe cardiac GV are at risk of sudden death and can benefit from early cardiac re-Tx.
Brain volumes in relatives of patients with schizophrenia: a meta-analysis.

CONTEXT Smaller brain volumes have consistently been found in patients with schizophrenia, particularly in gray matter and medial temporal lobe structures. Although several studies have investigated brain volumes in nonpsychotic relatives of patients with schizophrenia, results have been inconsistent. OBJECTIVE To determine the magnitude and extent of brain volume differences in first-degree relatives of schizophrenic patients. DATA SOURCES A systematic search was conducted to identify relevant studies. Computer searches of the MEDLINE database were performed for English-language articles published before July 2005. Relevant abstracts published in 2005 were also selected. STUDY SELECTION Magnetic resonance imaging studies that examined differences in brain volumes between first-degree relatives of patients with schizophrenia and healthy control subjects were obtained through computerized databases, including MEDLINE. Studies had to report sufficient data for computation of effect sizes. DATA EXTRACTION For each study, the Cohen d was calculated. Data extraction and calculation of the effect size were performed by 2 authors (H.B.M.B. and A.A.) who reached a consensus in cases of uncertainty and discrepancies. All analyses were performed using the random-effects model. DATA SYNTHESIS Twenty-five studies were identified as suitable for analysis and included 1065 independent first-degree relatives of patients, 679 patients with schizophrenia, and 1100 healthy control subjects. The largest difference between relatives and healthy control subjects was found in hippocampal volume, with relatives having smaller volumes than controls (d = 0.31; 95% confidence interval [CI], 0.13-0.49; 9 effect sizes). Gray matter was smaller (d = 0.18; 95% CI, 0.02-0.33; 7 effect sizes) and third-ventricle volume was larger (d = 0.21; 95% CI, 0.03-0.40; 7 effect sizes) in relatives compared with healthy control subjects. CONCLUSION Brain abnormalities are present in nonpsychotic first-degree relatives of patients with schizophrenia and are most pronounced in the hippocampus.
The Effects of TSH level on the Results of F-18 FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma Patients with Elevated Serum Thyroglobulin Level and Negative I-131 WBS.

Purpose : To assess the effects of TSH level on F-18 FDG PET-CT results & its impact on serum thyroglobulin (TG) cut off point and management in recurrent DTC patients with elevated TG level & negative I-131 WBS. Material and Methods: This prospective work involved 38 histopathologically proved DTC patients underwent total thyroid ablation with elevated serum TG and negative I-131 WBS during follow up. F-18 FDG was done in all patients using standard technique. Results: Patients divided into two groups: (I) Stimulated TSH group (i.e. TSH level > 30 IU/L, 60 ± 20 IU/L): 20 patients. (II) Suppressed TSH group (i.e. TSH level <0.1 IU/L, 0.007 ± 0.003IU/L): 18 patients. Significantly higher overall accuracy, sensitivity & NPV were found in stimulated group (98.5%, 88.6%, 62% respectively) compared to the suppressed group (66%, 62% & 31.5% respectively) that was more obvious in nodal rather than pulmonary deposits (P<0.05). However no significant difference was demonstrated in specificity & PPV between both groups. Significantly lower TG cut off point was demonstrated in stimulated group (15 ng/ml) compared to suppressed group (21 ng/ml) (P<0.05). Moreover significantly higher impact of F-18 FDG PET-CT in TSH stimulated (40%) was demonstrated compared to TSH suppressed (11.2%) group on
On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus

1 Histaminergic depression of excitatory synaptic transmission in the rat dentate gyrus was investigated using extracellular and whole‐cell patch‐clamp recording techniques in vitro. 2 Application of histamine (10 μm, 5 min) depressed synaptic transmission in the dentate gyrus for 1 h. This depression was blocked by the selective antagonist of histamine H3 receptors, thioperamide (10 μm). 3 The magnitude of the depression caused by histamine was inversely related to the extracellular Ca2+ concentration. Application of the N‐type calcium channel blocker ω‐conotoxin (0.5 or 1 μm) or the P/Q‐type calcium channel blocker ω‐agatoxin (800 nm) did not prevent depression of synaptic transmission by histamine. 4 The potassium channel blocker 4‐aminopyridine (4‐AP, 100 μm) enhanced synaptic transmission and reduced the depressant effect of histamine (10 μm). 4‐AP reduced the effect of histamine more in 2 mm extracellular calcium than in 4 mm extracellular calcium. 5 Histamine (10 μm) did not affect the amplitude of miniature excitatory postsynaptic currents (mEPSCs) and had only a small effect on their frequency. 6 Histaminergic depression was not blocked by an inhibitor of serine/threonine protein kinases, H7 (100 μm), or by an inhibitor of tyrosine kinases, Lavendustin A (10 μm). 7 Application of adenosine (20 μm) or the adenosine A1 agonist N6‐cyclopentyladenosine (CPA, 0.3 μm) completely occluded the effect of histamine (10 μm). 8 We conclude that histamine, acting on histamine H3 receptors, inhibits glutamate release by inhibiting presynaptic calcium entry, via a direct G‐protein‐mediated inhibition of multiple calcium channels. Histamine H3 receptors and adenosine A1 receptors act upon a common final effector to cause presynaptic inhibition.
Positivity and incidence of human papillomavirus in women attending gynecological department of a major comprehensive hospital in Kunming, China 2012–2014

HPV DNA testing is receiving increasing popularity in cervical cancer screening. There is a lack of universal guidelines on HPV testing. Our study aimed to assess age‐specific and year‐on‐year trend of HPV positivity and incidence and HPV retesting among 26,457 individual women attending the gynecological department at the First People's Hospital of Yunnan Province (FPHY) who had an HPV testing between January 1, 2012 and December 31, 2014. HPV 16, HPV 52, and cp8304 ranked among top 5 with regard to positivity in each year and overall incidence. The positivity of various HPV types peaked among women aged 15–19 years, then sharply decreased with age, stabilized among women aged 25–49 years and then surged again among women aged 50 years and older. The positivity of high‐risk (HR) HPV types, including HPV 16, 18, 31, 33, 56 and 58, were on the rise during the time period (P < 0.05 for all). HR HPV types tended to be more likely to persist than LR HPV types (P < 0.05). Additionally, the incidence rate for any HR HPV type was also significantly higher than that for any LR HPV type (42.8 vs. 12.6 per 100 person‐years, P < 0.001). The majority (57.3–77.5%) of women detected with HR HPV types did not retest within 12 months. Clinical guidelines on HPV DNA testing are needed and education, and counseling about HPV infection and its implications for women detected with HPV at clinical settings, are warranted. J. Med. Virol. 88:703–711, 2016. © 2015 Wiley Periodicals, Inc.
Title : The role of ghrelin signalling in second-generation antipsychotic-induced weight gain

Based on clinical and animal studies, this review suggests a tri-phasic effect of second-generation antipsychotics (SGAs) on circulating ghrelin levels: an initial increase exerted by the acute effect of SGAs; followed by a secondary decrease possibly due to the negative feedback from the SGA-induced body weight gain or hyperphagia; and a final re-increase to reach the new equilibrium. Moreover, the results can also vary depending on individual SGAs, other hormonal states, dietary choices, and other confounding factors including medical history, co-treatments, age, gender, and ghrelin measurement techniques. Interestingly, rats treated with olanzapine, an SGA with high weight gain liabilities, are associated with increased hypothalamic ghrelin receptor (GHS-R1a) levels. In addition, expressions of downstream ghrelin signalling parameters at the hypothalamus, including neuropeptide Y (NPY)/agouti-related peptide (AgRP) and proopiomelanocortin (POMC) are also altered under SGA treatments. Thus, understanding the role of ghrelin signalling in antipsychotic drug-induced weight gain should offer potential novel pharmacological targets for tackling the obesity side-effect of SGAs and its associated metabolic syndrome.
Outcomes of Small Cell Lung Cancer Patients Treated With Cisplatin-Etoposide Versus Carboplatin-Etoposide

Purpose:This descriptive study compares overall survival (OS) and locoregional control (LRC) rates between cisplatin-etoposide (EP) and carboplatin-etoposide (EC) at a population level in patients with limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC). Materials and Methods:All patients diagnosed with SCLC from January 2004 to December 2008 were identified. Patients with LD SCLC treated with EP or EC and concurrent or sequential radiotherapy and those with ED SCLC treated with EP or EC were included for analysis. A retrospective review examining prognostic features and outcomes was performed. OS and LRC curves were calculated using the Kaplan-Meier method and compared with the log-rank test. Results:A total of 249 patients with LD SCLC and 287 patients with ED SCLC were identified. Patients treated with EC were significantly older for both LD (median 62 vs. 72, P<0.001) and ED (median 62 vs. 73, P<0.001). Median follow-up times were 37 and 22 months for LD and ED SCLC, respectively. Median OS for EP and EC in LD SCLC patients were 23 and 18 months (P=0.10). LRC rates at 12 months were 81% for the EP group and 68% for the EC group (P=0.97). Median OS for the EP and EC patients with ED SCLC was 10 and 11 months, respectively, (P=0.24). Conclusion:Despite the preferential use of EC in an older population, median OS and LRC rates were not significantly different for patients treated with EP for both LD and ED SCLC.