Miracle-dz/UniFAR-FTUs huggingface dataset:
Processing and Presentation of Exogenous HLA Class I Peptides by Dendritic Cells from Human Immunodeficiency Virus Type 1-Infected Persons

ABSTRACT Dendritic cells (DCs) loaded with viral peptides are a potential form of immunotherapy of human immunodeficiency virus type 1 (HIV-1) infection. We show that DCs derived from blood monocytes of subjects with chronic HIV-1 infection on combination antiretroviral drug therapy have increases in expression of HLA, T-cell coreceptor, and T-cell activation molecules in response to the DC maturation factor CD40L comparable to those from uninfected persons. Mature DCs (mDCs) loaded with HLA A*0201-restricted viral peptides of the optimal length (9-mer) were more efficient at activating antiviral CD8+ T cells than were immature DCs or peptide alone. Optimal presentation of these exogenous peptides required uptake and vesicular trafficking and was comparable in DCs derived from HIV-1-infected and uninfected persons. Furthermore, DCs from HIV-1-infected and uninfected persons had similar capacities to process viral peptides with C-terminal and N-terminal extensions through their proteasomal and cytosolic pathways, respectively. We conclude that DCs derived from HIV-1-infected persons have similar abilities to process exogenous peptides for presentation to CD8+ T cells as those from uninfected persons. This conclusion supports the use of DCs loaded with synthetic peptides in immunotherapy of HIV-1 infection.
Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group.

PURPOSE In 1984, the Department of Veterans Affairs Cooperative Studies Program began a trial in which patients with resectable squamous cell carcinoma of the larynx were randomized to receive standard surgery followed by radiation therapy or to receive neoadjuvant therapy with cisplatin and fluorouracil (5-FU) followed by radiation therapy for those achieving a greater than 50% tumor response to chemotherapy. This analysis reviews the tumor responses, toxicity, compliance, and long-term survival for those patients randomized to the chemotherapy arm. PATIENTS AND METHODS One hundred sixty-six patients were randomized to the chemotherapy arm. Standard tumor response data, chemotherapy toxicity, and survival have been examined using standard statistical methods. RESULTS The high response rates and acceptable toxicity to cisplatin and 5-FU of previously untreated patients were confirmed. Long-term disease-free survival was more likely to occur in patients who achieved a complete response to chemotherapy, particularly in those who had a confirmed histologic response to chemotherapy. Pretreatment histologic growth patterns were highly predictive of responses to chemotherapy. CONCLUSION Neoadjuvant chemotherapy was well tolerated and did not negatively affect the definitive treatment that followed. The survival of nonresponding patients who underwent prompt salvage surgery was also not impaired. The role of organ preservation should be explored in other head and neck sites.
Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis.

RATIONALE The kinetics of Mycobacterium tuberculosis-specific Th1-type T-cell responses after M. tuberculosis infection are likely to be important in determining clinical outcome. OBJECTIVE To investigate the kinetics of T-cell responses, in the context of a point-source school tuberculosis outbreak, in three groups of contacts who differed by preventive treatment status and tuberculin skin test (TST) results: 38 treated TST-positive students, 11 untreated TST-positive staff, and 14 untreated students with negative or borderline TST results. METHODS We used the ex vivo IFN-gamma enzyme-linked immunospot assay (ELISpot) to track T cells specific for two region of difference 1 (RD1) antigens, early secretory antigenic target 6 and culture filtrate protein 10, for 18 mo after cessation of tuberculosis exposure. MAIN RESULTS The treated TST-positive students had an average 68% decline in frequencies of RD1-specific IFN-gamma-secreting T cells per year (p < 0.0001) and 6 of 38 students had no detectable RD1-specific T cells by 18 mo. No change in frequencies of these cells was observed in the untreated TST-positive staff (p = 0.38) and none were ELISpot-negative at 18 mo. Of the 14 untreated students, 7 were persistently ELISpot-positive (all of whom had borderline TST results), and 7 became ELISpot-negative (all but one had negative TST results) during follow-up. CONCLUSIONS The decrease in M. tuberculosis-specific T cells and their disappearance in a proportion of treated students likely reflect declining antigenic and bacterial load in vivo induced by antibiotic treatment. The observed disappearance of M. tuberculosis-specific T cells in the untreated TST-negative contacts suggests that an acute resolving infection may occur in some contacts.
Correlation Between Serum 25‐Hydroxyvitamin D and Virulence Genes of Staphylococcus aureus Isolates Colonizing Children with Atopic Dermatitis

The skin of children with atopic dermatitis (AD) is colonized with Staphylococcus aureus more frequently than that of their peers. We investigated the prevalence of skin and nares colonization by S. aureus in children with AD, the virulence genes of the isolates, and their association with allergy, AD severity, and serum vitamin D (25(OH)D). This was an observational, cross‐sectional study in a sample of children diagnosed with AD in two settings in Spain. The samples were collected in 2012. Swabs from affected skin and nares were taken for microbiologic culture. The prevalence of S. aureus and presence of 17 staphylococcal virulence genes were studied using polymerase chain reaction. A total of 114 patients with a mean age of 5.7 ± 4.1 (range 3 mos to 14 yrs) were included in the study. Swabs were taken from the skin of 113 individuals with AD and from the nares of 85; 28.3% had S. aureus on the skin, which was significantly associated with positive allergen‐specific immunoglobulin E antibodies and higher Scoring Atopic Dermatitis (SCORAD) scores in the multivariate analysis. The presence of virulence factors tsst‐1, eta, cna, aur, and sec in cutaneous S. aureus isolates was associated with lower serum levels of 25(OH)D. S. aureus on nasal swabs correlated with its presence on the skin and was associated with lower 25(OH)D levels. In conclusion, S. aureus colonization is associated with allergy and severity in AD, whereas certain virulence genes are associated with lower serum 25(OH)D levels.
Culture-Dependent and Culture-Independent Characterization of Microbial Assemblages Associated with High-Temperature Petroleum Reservoirs

ABSTRACT Recent investigations of oil reservoirs in a variety of locales have indicated that these habitats may harbor active thermophilic prokaryotic assemblages. In this study, we used both molecular and culture-based methods to characterize prokaryotic consortia associated with high-temperature, sulfur-rich oil reservoirs in California. Enrichment cultures designed for anaerobic thermophiles, both autotrophic and heterotrophic, were successful at temperatures ranging from 60 to 90°C. Heterotrophic enrichments from all sites yielded sheathed rods (Thermotogales), pleomorphic rods resemblingThermoanaerobacter, and Thermococcus-like isolates. The predominant autotrophic microorganisms recovered from inorganic enrichments using H2, acetate, and CO2 as energy and carbon sources were methanogens, including isolates closely related to Methanobacterium,Methanococcus, and Methanoculleus species. Two 16S rRNA gene (rDNA) libraries were generated from total community DNA collected from production wellheads, using either archaeal or universal oligonucleotide primer sets. Sequence analysis of the universal library indicated that a large percentage of clones were highly similar to known bacterial and archaeal isolates recovered from similar habitats. Represented genera in rDNA clone libraries includedThermoanaerobacter, Thermococcus,Desulfothiovibrio, Aminobacterium,Acidaminococcus, Pseudomonas,Halomonas, Acinetobacter,Sphingomonas, Methylobacterium, andDesulfomicrobium. The archaeal library was dominated by methanogen-like rDNAs, with a lower percentage of clones belonging to the Thermococcales. Our results strongly support the hypothesis that sulfur-utilizing and methane-producing thermophilic microorganisms have a widespread distribution in oil reservoirs and the potential to actively participate in the biogeochemical transformation of carbon, hydrogen, and sulfur in situ.
Impact of postoperative cusp configuration on midterm durability after aortic root reimplantation.

BACKGROUND AND AIM OF THE STUDY The study aim was to examine the echocardiographic features associated with recurrent aortic regurgitation (AR) after valve-preserving aortic root reconstruction surgery. METHODS Echocardiographic data from 86 patients who underwent aortic root replacement with or without cusp repair were retrospectively reviewed. An analysis was conducted of the height difference between the level of the ventriculoaortic junction (VAJ) and the central free margin of the cusp, defined as the effective height (EH), and the length from the aortic annulus to the edge of the body of Arantius, defined as the geometric height (GH), in addition to root dimensions (diameter of VAJ, sinus of Valsalva, and sinotubular junction). RESULTS All patients presented with < or = mild AR at discharge. After a median follow up duration of 46.4 months, the development of moderate AR or greater was observed in 14 patients. The overall actuarial freedom from moderate AR or greater, and freedom from reoperation at three and five years were 86.2 +/- 4.4% and 81.8 +/- 5.2%, and 94.0 +/- 3.0% and 91.8 +/- 3.6%, respectively. The postoperative EH (7.47 +/- 3.3 mm in > mild AR group, versus 8.81 +/- 2.1 mm in < or = mild AR group, p = 0.049), the incidence of postoperative eccentric jet (57.1% in > mild AR group versus 12.5% in < or = mild AR group, p = 0.0005) and cusp billowing (78.6% in > mild AR group versus 20.8% in < or = mild AR group, p < 0.0001) were significantly correlated with > mild AR in the follow up. There was also correlation between postoperative EH and the severity of recurrent AR at follow up (p = -0.33, p = 0.0019). CONCLUSION Objective information on cusp configuration, such as EH, should play an important role in stabilizing the outcome of valve-sparing surgery.
Intergenerational Disadvantage: Learning About Equal Opportunity from Social Assistance Receipt

We use variation in the extent of generational persistence across social assistance payments to shed light on the factors leading to intergenerational disadvantage. Our administrative data come from the Australian social security system and provide us with detailed social assistance trajectories – across the entire social safety net – for a birth cohort of young people and their families over an 18-year period. We find that young people are 1.8 times more likely to need social assistance if their parents have a history of receiving social assistance themselves. These young people also receive more intensive support; an additional $12,000 over an 8-year period. The intergenerational correlation is particularly strong in the case of disability payments, payments for those with caring responsibilities, and parenting payments for single parents. Disadvantage stemming from parents’ poor labor market outcomes seems to be easier for young people to overcome. This suggests that parental disadvantage may be more harmful to children’s later life outcomes if it is more strongly driven by circumstances rather than personal choice.
Proinflammatory Responses and Higher IL-10 Production by T Cells Correlate with Protection against Malaria during Pregnancy and Delivery Outcomes

Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been properly addressed whether similar changes occur in tropical areas with high infection pressure and whether these changes render women more susceptible to infectious diseases. We compared the frequencies of T cell subsets, including regulatory T cells, in pregnant and nonpregnant women from Papua New Guinea, a high malaria transmission area, and from Spain, a malaria-free country. We also assessed the relationship among these cellular subsets, malaria infection, and delivery outcomes. CD4+FOXP3+CD127low T cells (Tregs) were decreased in pregnant women in both countries but were not associated with malaria infection or poor delivery outcomes. An expansion of IFN-γ–producing cells and intracytoplasmic IFN-γ levels was found in pregnant compared with nonpregnant women only in Papua New Guinea. Increased CD4+IL-10+IFN-γ+ frequencies and Treg–IFN-γ production were found in women with current Plasmodium falciparum infection. Higher CD4+IL-10−IFN-γ+ T cells frequencies and production of proinflammatory cytokines (including TNF and IL-2) at recruitment (first antenatal visit) had a protective association with birth weight and future (delivery) P. falciparum infection, respectively. Higher intracellular IL-10 levels in T cells had a protective association with future P. falciparum infection and hemoglobin levels at delivery. The protective associations were found also with nonmalaria-specific T cell responses. Treg frequencies positively correlated with plasma eotaxin concentrations, but this subset did not express eotaxin receptor CCR3. Thus, an activated immune system during pregnancy might contribute to protection against malaria during pregnancy and poor delivery outcomes.
Prostacyclin Deficiency and Reduced Fetoplacental Blood Flow in Pregnancy-Induced Hypertension and Preeclampsia

Background: Low endothelial generation of prostacyclin (PGI2) is a typical feature of pregnancy-induced hypertensive disorders. The aim of the current study was to establish whether changes in PGI2 are accompanied by alterations in fetoplacental blood flow and to test the hypothesis that PGI2 deficiency contributes to reduced fetoplacental perfusion in pregnancy-induced hypertension (PIH) and preeclampsia. Methods: The study included 11 women with normal pregnancies, 12 with PIH/preeclampsia, and 7 with otherwise complicated pregnancies. Fetoplacental blood flow was assessed both by umbilical artery Doppler sonography measuring the resistance index (RI) and by means of neonatal birth weight. PGI2 formation was measured in umbilical arteries prepared immediately after birth. PGI2, RI and birth weight were correlated with and without correction for gestational age. Furthermore, data from patients with PIH/preeclampsia were compared with normal pregnancies as controls. Results: A significant inverse correlation was found between umbilical PGI2 formation and umbilical RI and between birth weight and RI, whereas PGI2 and birht weight were directly related. Patients with PIH/preeclampsia showed reduced PGI2 formation, markedly increased gestational age-corrected RI and significantly reduced percentile birth weight. Conclusions: These results provide evidence showing that PGI2 is a relevant mediator of fetoplacental blood flow and suggest an important role of PGI2 deficiency in PIH/preeclampsia.
Differential processing of sindbis virus glycoprotein PE2 in cultured vertebrate and arthropod cells

A step in the maturation of Sindbis virus glycoproteins is the cleavage of the precursor glycoprotein PE2 into E3 and E2 by furin or a furin-like host cell protease. The results presented here suggest that PE2 cleavage is an obligatory event for Sindbis virus maturation in C6/36 cells and demonstrate that certain mutants display a cell-specific PE2 cleavage phenotype. We previously have described Sindbis virus variants which fail to cleave PE2 because of incorporation of a signal for N-linked glycosylation immediately adjacent to the PE2 cleavage site but are viable in BHK-21 cells by virtue of an additional mutation at E2 216 or E2 191 (TRSB-NE2G216 and TRSB-NE2T191, respectively) (H. W. Heidner, K. L. McKnight, N. L. Davis, and R. E. Johnston, J. Virol. 68:2683-2692, 1994). Other viable PE2 cleavage-defective mutants were constructed by substituting the parental residue at E2 position 1 (Arg), with Leu or Val (TRSB-E2L1 and TRSB-E2V1, respectively) (H.W. Heidner and R. E. Johnston, J. Virol. 68:8064-8070, 1994). When grown in BHK-21 cells, all four of these viruses replicated normally and incorporated PE2 in place of E2 in released virions. However, growth of TRSB-NE2G216 and TRSB-NE2T191 was severely restricted in cultured arthropod cells (C6/36 cells). Analysis of infected C6/36 cells by flow cytometry demonstrated that the restricted growth of TRSB-NE2G216 and TRSB-NE2T191 was not due to an impaired ability to initiate infection. In addition, TRSB-NE2G216 and TRSB-NE2T191 remained growth restricted in C6/36 cells following introduction of in vitro transcriptions by electroporation. In contrast, the PE2 cleavage defect of TRSB-E2L1 and TRSB-E2V1 was cell type specific. In C6/36 cells, the majority of PE2 was converted to E2, and these viruses replicated normally in C6/36 cells. These results demonstrated a consistent link between expression of a PE2 cleavage defect and restricted growth in C6/36 cells and suggest that cleavage of PE2 is required for maturation of Sindbis virus late in infection of C6/36 cells.
Limbic Encephalitis Associated With Elevated Antithyroid Antibodies

Immune-mediated limbic encephalitis affects both adults and children. Patients typically present with seizures, memory problems, and imaging changes in the medial temporal lobes. Both paraneoplastic and nonparaneoplastic forms have been described in which the antibody to the voltage-gated potassium channel-complex associated protein, leucine-rich glioma-inactivated 1, is most commonly reported. Elevated antithyroid antibodies have also been reported in a range of neurological syndromes with encephalopathy, such as limbic encephalitis, often collectively termed Hashimoto encephalopathy, a condition whereby corticosteroids responsiveness with a complete recovery is commonly observed. Here we describe 3 children presenting with limbic encephalitis with elevated thyroid antibodies that did not respond to corticosteroids alone and required more aggressive immunotherapy, mirroring the slower treatment response that is more frequently seen in other immune-mediated forms of limbic encephalitis.
Mental disorders in the entrepreneurship context : When Being Different Can Be an Advantage

Mental disorders are prevalent, place considerable burden on the economy and lead to suffering for those with the disorders and their loved ones. However, there is a flipside. Evidence suggests that people with mental disorders can flourish and productively contribute to society through entrepreneurship. This paper explores the relationship between mental disorders and entrepreneurship. It builds a research agenda to propose that researchers explore the role of mental disorders in the entrepreneurial context. We show how such research will advance this new field of research, but also how it can develop novel insights and theories in entrepreneurship and contribute to theories on the psychology of work, career choice, and clinical psychology.
Ultrafast Papanicolaou Stain Modified for Developing Countries: Efficacy and Pitfalls

Objective: To study the efficacy of the ultrafast Papanicolaou (UFP) staining technique for immediate cytologic diagnosis, to check specimen adequacy during radiologically guided fine needle aspiration cytology (FNAC) procedures and to objectively assess the quality of UFP stain and factors affecting it. Study Design: Serial and random samples of cytologic material from 347 patients during a 2-year period were divided in 3 groups. Group I included 238 outpatient FNACs, group II included 59 radiologically guided FNACs, and group III included 50 cases of intraoperative cytology. After staining air-dried smears with UFP stain, immediate diagnosis was given. In group II, material adequacy was also conveyed to the radiologist. Results: Overall diagnosis was possible in 297 (85.6%) cases. Only 8 (2.3%) cases could not be diagnosed due to staining difficulties. The overall concordance rate was 98%. Seventy-five percent of cases showed ‘excellent’ and ‘good’ morphology, allowing easy diagnosis. In 25% of ‘fair’ cases diagnosis was still possible, although with some difficulties. Factors affecting the quality of staining are discussed. Conclusion: The UFP staining technique is an accurate and reliable method for rapid cytology reporting. It significantly reduces total turn around time of the test result, thereby having the potential to be cost-effective, both for the patient and the hospital.
Connecting organisational culture and quality of care in the hospital: is job burnout the missing link?

PURPOSE To date, relatively little evidence has been published as to what represents an effective and efficient way to improve quality of care and safety in hospitals. In addition, the initiatives that do exist are rarely designed or developed with regard to the individual and organisational factors that determine the success or failure of such initiatives. One of the challenges in linking organisational culture to quality of care is to identify the focal point at which a deficient hospital culture and inadequate organisational resources are most evident. The accumulated evidence suggests that such a point is physician burnout. This paper sets out to examine this issue. DESIGN/METHODOLOGY/APPROACH The paper reviews the existing literature on organisational culture, burnout and quality of care in the healthcare sector. A new conceptual approach as to how organisational culture and quality of care can be more effectively linked through the physician experience of burnout is proposed. FINDINGS Recommendations are provided with regard to how future research can approach quality of care from a bottom-up organisational change perspective. In addition, the need to widen the debate beyond US and North European experiences is discussed. ORIGINALITY/VALUE The present paper represents an attempt to link organisational culture, job burnout and quality of care in a more meaningful way. A conceptual model has been provided as a way to frame and evaluate future research.
Stool viruses among paediatric patients from a Nairobi clinic, Kenya.

OBJECTIVE To document the clinical presentation and prevalence of stool viruses among children presenting with symptoms of acute gastroenteritis (AGE) at Gertrude's Garden Children's Hospital, Nairobi, Kenya. DESIGN Retrospective case-control study. SETTING A private paediatric clinic in Nairobi. RESULTS Viral antigen was detectable in the stool samples of 21 (rotavirus alone in ten cases, adenovirus alone in seven cases, and both viruses in four cases). Diarrhoea was almost universally present (20/21 cases) and was reported more frequently than in a control group of ten children with clinical acute gastroenteritis whose stools tested negative for viruses. Fever, an elevated total leukocyte count, and neutrophilia were commonly observed in patients with viral gastroenteritis. Eight children with viral AGE were treated with antibiotics and eight children were admitted to hospital. CONCLUSION A viral etiology can frequently be identified among children in Nairobi with AGE. Fever, an elevated leukocyte count, and neutrophilia were not helpful in differentiating viral from non-viral AGE in this series. Supportive management consisting of outpatient oral rehydration therapy without antibiotic treatment should be considered in the non-toxic child with AGE.
Bone mineral density in patients with Crohn's disease during long‐term treatment with azathioprine

Florén C‐H, Ahrén B, Bengtsson M, Bartosik J, Obrant K (Lund University, Malmö, Sweden). Bone mineral density in patients with Crohn's disease during long‐term treatment with azathioprine. J Intern Med 1998; 243: 123–26.