bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control
Authors: Steffensen Maria A. , Pedersen Louise H. , Jahn Marie L. , Nielsen Karen N. , Christensen Jan P. , Thomsen Allan R. 
Published: February 2016

Abstract
As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag to a vaccine expressing the same Ag without its immunodominant epitope. We found that removal of the dominant epitope allowed the induction of CD8+ T cell responses targeting at least two otherwise subdominant epitopes. Importantly, the overall magnitude of the induced T cell responses was similar, allowing us to directly compare the efficiency of these vaccines. Doing this, we observed that mice vaccinated with the vaccine expressing unmodified Ag more efficiently controlled an acute viral challenge. In the course of a more chronic viral infection, mice vaccinated using the vaccine targeting subdominant epitopes caught up with the conventionally vaccinated mice, and analysis of the breadth of the CD8+ T cell response revealed that this was notably greater in the former mice. However, under the conditions of our studies, we never saw any functional advantage of this. This may represent a limitation of our model, but clearly our findings underscore the importance of carefully weighing the pros and cons of changes in epitope targeting before any implementation.
Rapid Evolution of the CD8+ TCR Repertoire in Neonatal Mice
Authors: Carey Alison J. , Gracias Donald T. , Thayer Jillian L. , Boesteanu Alina C. , Kumova Ogan K. , Mueller Yvonne M. , Hope Jennifer L. , Fraietta Joseph A. , van Zessen David B. H. , Katsikis Peter D. 
Published: February 2016

Abstract
Currently, there is little consensus regarding the most appropriate animal model to study acute infection and the virus-specific CD8+ T cell (CTL) responses in neonates. TCRβ high-throughput sequencing in naive CTL of differently aged neonatal mice was performed, which demonstrated differential Vβ family gene usage. Using an acute influenza infection model, we examined the TCR repertoire of the CTL response in neonatal and adult mice infected with influenza type A virus. Three-day-old mice mounted a greatly reduced primary NP(366–374)–specific CTL response when compared with 7-d-old and adult mice, whereas secondary CTL responses were normal. Analysis of NP(366–374)-specific CTL TCR repertoire revealed different Vβ gene usage and greatly reduced public clonotypes in 3-d-old neonates. This could underlie the impaired CTL response in these neonates. To directly test this, we examined whether controlling the TCR would restore neonatal CTL responses. We performed adoptive transfers of both nontransgenic and TCR-transgenic OVA(257–264)-specific (OT-I) CD8+ T cells into influenza-infected hosts, which revealed that naive neonatal and adult OT-I cells expand equally well in neonatal and adult hosts. In contrast, nontransgenic neonatal CD8+ T cells when transferred into adults failed to expand. We further demonstrate that differences in TCR avidity may contribute to decreased expansion of the endogenous neonatal CTL. These studies highlight the rapid evolution of the neonatal TCR repertoire during the first week of life and show that impaired neonatal CTL immunity results from an immature TCR repertoire, rather than intrinsic signaling defects or a suppressive environment.
Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication
Authors: Kohler Stephanie L. , Pham Michael N. , Folkvord Joy M. , Arends Tessa , Miller Shannon M. , Miles Brodie , Meditz Amie L. , McCarter Martin , Levy David N. , Connick Elizabeth 
Published: February 2016

Abstract
HIV-1 replication is concentrated within CD4+ T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus–producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5highPD-1high) and CXCR5+programmed cell death-1 (PD-1)low cells were GFP+ than non-GC TFH (CXCR5+PD-1intermediate) or extrafollicular (EF) (CXCR5−) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5+PD-1low or EF cells, suggesting that many GC TFH transition to a CXCR5+PD-1low phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1–infected individuals without AIDS revealed higher frequencies of HIV-1 RNA+ cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1–infected individuals’ lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5+CD4+ cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5+ subsets harbored 11–66-fold more HIV-1 RNA than CXCR5− subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1–producing cells in chronic asymptomatic HIV-1 infection.
Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans
Authors: Cuesta Marc , Boudreau Philippe , Dubeau-Laramée Geneviève , Cermakian Nicolas , Boivin Diane B. 
Published: February 2016

Abstract
Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5–6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep–wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers.
Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans
Authors: Currie Silke M. , Gwyer Findlay Emily , McFarlane Amanda J. , Fitch Paul M. , Böttcher Bettina , Colegrave Nick , Paras Allan , Jozwik Agnieszka , Chiu Christopher , Schwarze Jürgen , Davidson Donald J. 
Published: February 2016

Abstract
Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection in infants, causing significant morbidity and mortality. No vaccine or specific, effective treatment is currently available. A more complete understanding of the key components of effective host response to RSV and novel preventative and therapeutic interventions are urgently required. Cathelicidins are host defense peptides, expressed in the inflamed lung, with key microbicidal and modulatory roles in innate host defense against infection. In this article, we demonstrate that the human cathelicidin LL-37 mediates an antiviral effect on RSV by inducing direct damage to the viral envelope, disrupting viral particles and decreasing virus binding to, and infection of, human epithelial cells in vitro. In addition, exogenously applied LL-37 is protective against RSV-mediated disease in vivo, in a murine model of pulmonary RSV infection, demonstrating maximal efficacy when applied concomitantly with virus. Furthermore, endogenous murine cathelicidin, induced by infection, has a fundamental role in protection against disease in vivo postinfection with RSV. Finally, higher nasal levels of LL-37 are associated with protection in a healthy human adult RSV infection model. These data lead us to propose that cathelicidins are a key, nonredundant component of host defense against pulmonary infection with RSV, functioning as a first point of contact antiviral shield and having additional later-phase roles in minimizing the severity of disease outcome. Consequently, cathelicidins represent an inducible target for preventative strategies against RSV infection and may inform the design of novel therapeutic analogs for use in established infection.
Bangkok Men’s Attitudes towards Marital Rape
Authors: Jermsittiparsert Kittisak , Kasemsukphaisit Paranee 
Published: February 2016

<p class="Body">This research aims (i) to explore Bangkok men’s understandings of section 276 of the criminal code; (ii) to examine the attitudes on marital rape as perceived by men in Bangkok and to conduct a comparative study on the observed attitudes using various demographic assessment factors, namely, age, marital status, occupation, and income level; (iii) to investigate the correlations between the level of understandings of the relevant law and the attitudes of men living in Bangkok on marital rape by employing quantitative research method, with the use of questionaries that would collect data from 280 research subjects. The data analysis is carried out using frequency, mean, percentage, one-way analysis of variance, least significant difference (LSD), and Pearson product-moment correlation coefficient analysis with significance level 0.5.</p><p class="Body">The research findings indicates that the subjects possess the least understandings of section 276 of the criminal code ( = .15) and contain average level of attitudes with respect to the issue of marital rape ( = 3.19). When examining with different assessment factors, it is found that the subjects bare an attitude of cognition at low level ( = 2.22), of feelings at average level ( = 3.36), and of action tendency at considerable level ( = 3.98). Results from the comparative analysis on different levels of attitudes over the issue of marital rape, using different demographic assessment factors, reveal that the difference in income generates different level of attitudes whereas the differences in age, marital status and occupation bare relatively similar level of attitudes. Lastly, no correlation is found when looking at the outcome of the correlation analysis between level of understandings and attitudes perceived.</p>
Comparison of classic terminology with the FIGO PALM‐COEIN system for classification of the underlying causes of abnormal uterine bleeding
Authors: Töz Emrah , Sancı Muzaffer , Özcan Aykut , Beyan Emrah , İnan Abdurrahman H 
Published: February 2016

AbstractObjectiveTo compare classic terminology and the PALM‐COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory disorders, endometrium, iatrogenic, and not classified) classification system among women who underwent surgery for abnormal uterine bleeding (AUB), and to subclassify the components of the PALM group for future studies.MethodsIn a retrospective study, data were obtained for nonpregnant women aged 18–55 years who underwent hysterectomy, myomectomy, or polypectomy for AUB at a center in Turkey in 2014. The patients were retrospectively classified according to the PALM‐COEIN system, and the two terminologies were compared.Results: A total of 471 women were included. The term “hypermenorrhea” covered 15 different pathology combinations, “menorrhagia” nine, “metrorrhagia” 14, and “menometrorrhagia” 18. Of 92 patients with polyp, 5 (5.4%) had two polyps and 1 (1.1%) had three. Of 146 patients with adenomyosis, 131 (89.7%) had diffuse adenomyosis and 12 (8.2%) had adenomyoma. Of 309 patients with myoma uteri, 108 (34.9%) had submucous myoma and 201 (65.1%) had other types of myoma.ConclusionClassic terminology for AUB is insufficient and confusing with respect to etiologic pathologies among nonpregnant women of reproductive age. Widespread adoption of the PALM‐COEIN system for AUB classification will facilitate more meaningful communication among both clinicians and investigators, and clarify the populations that should be evaluated in clinical trials, thereby enhancing communication with patients.
Multicenter analysis comparing robotic, open, laparoscopic, and vaginal hysterectomies performed by high‐volume surgeons for benign indications
Authors: Lim Peter C. , Crane John T. , English Eric J. , Farnam Richard W. , Garza Devin M. , Winter Marc L. , Rozeboom Jerry L. 
Published: February 2016

AbstractObjectiveTo compare perioperative outcomes between robotic‐assisted benign hysterectomies and abdominal, vaginal, and laparoscopic hysterectomies when performed by high‐volume surgeons.MethodsA multicenter data analysis compared 30‐day outcomes from consecutive robotic‐assisted hysterectomies performed by high‐volume surgeons (≥ 60 prior procedures) at nine centers with records retrieved from the Premier Perspective database for abdominal, vaginal, and laparoscopic hysterectomies performed by high‐volume gynecologic surgeons. Data on benign hysterectomy disorders from January 1, 2012 to September 30, 2013 were included.ResultsData from 2300 robotic‐assisted, 9745 abdominal, 8121 vaginal, and 11 952 laparoscopic hysterectomies were included. The robotic‐assisted patient cohort had a significantly higher rate of adhesive disease compared with the vaginal (P < 0.001) and laparoscopic cohorts (P < 0.001), a significantly higher rate of morbid obesity than the vaginal (P < 0.001) or laparoscopic cohorts (P < 0.001), and a significantly higher rate of large uteri (> 250 g) than the abdominal (P < 0.001), vaginal (P < 0.001), or laparoscopic cohorts (P = 0.017). The robotic‐assisted cohort experienced significantly fewer intraoperative complications than the abdominal (P < 0.001) and vaginal cohorts (P < 0.001), and experienced significantly fewer postoperative complications compared with all the comparator cohorts (P < 0.001).ConclusionWhen performed by gynecologic surgeons with relevant high‐volume experience, robotic‐assisted benign hysterectomy provided improved outcomes compared with abdominal, vaginal, and laparoscopic hysterectomy.
Prevalence of and Risk Factors for Skin Diseases Among Army Personnel and Flood Victims During the 2011 Floods in Thailand
Authors: Thongtaeparak Wittaya , Pratchyapruit Walai-orn , Kotanivong Settha , Sirithanakit Nimit , Thunyaharn Sudaluck , Rangsin Ram , Chaikaew Phachara , Wongyongsin Pitee , Pinyoboon Pongpak , Sutthiwan Phatcharaphan , Theethansiri Witchwaree , Janthayanont Dusit , Mungthin Mathirut 
Published: February 2016

AbstractObjectiveThis study aimed to determine the prevalence of and risk factors for skin problems among flood victims and army personnel during the 2011 floods in Thailand.MethodsTo determine the prevalence of and risk factors for skin symptoms, standardized questionnaires were used to collect demographic data, current skin symptoms, history of water exposure, and sanitary behaviors. A certified dermatologist evaluated those who presented with skin problems and provided diagnoses. Univariate and multivariate analyses were performed to assess independent risk factors for skin symptoms.ResultsThe most prevalent skin disease was irritant contact dermatitis. Flood victims showed a higher prevalence of skin symptoms compared with army personnel. Development of skin symptoms after exposure to floodwater was also observed earlier among flood victims. Having a history of skin diseases and delayed skin cleaning after exposure were also significant risk factors for the development of skin symptoms.ConclusionThis information might be used as guidelines for protecting military personnel and to educate the general public regarding flood disaster management. (Disaster Med Public Health Preparedness. 2016;10:570–575)
The Justification of Punishment: A Comment on Retribution and Deterrence
Authors: Gur-Arye Miriam 
Published: February 2016

In this comment I wish to defend Antony Duff's final conclusion; namely, that punishment is to be seen as a deterrent system constrained by requirements of justice. I shall do this, however, mainly by using John Kleinig's arguments. My aim is to show that although Kleinig himself rejects deterrence as part of punishment's justification, some of his arguments can best be defended if deterrence is taken into account. In the final section of the comment I shall return to Duff's arguments in this context, but only in order to raise some doubts as to their underlying assumption.Before doing so, let me compare, briefly, Duff's and Kleinig's attitudes which seem to be relevant to the purpose of this comment.Both Kleinig and Duff believe that, ideally, punishment is to be justified by retributive considerations. According to Kleinig, even in such an imperfect society as ours, punishment should still remain retributive.
The Current Profile of Capital Punishment
Authors: Mosk Stanley 
Published: February 2016

In a way, I suppose, everything has been said about the death penalty that can be said. Yet we continue to discuss the penalty, the legal processes involved, the actual means of execution, the crimes for which death is to be imposed, and at the cornerstone, the moral justification for society deliberately taking human lives.At the risk of appearing immodest, I claim to be peculiarly equipped to enter into this discussion because I have been on all sides of the issue — not, I hasten to explain, because of unconcern or ambivalence. First, as an idealistic young man, I debated for abolition of the death penalty. Then, as executive secretary to the Governor of California, I had the duty of actually interviewing, in prison, men — and one woman — under sentence of death and making a report to the Governor. He, in turn, had the responsibility of commuting some sentences to life and allowing others to go to their death.
Reflections on Capital Punishment
Authors: Schwarzschild Henry 
Published: February 2016

I, too, want to express my gratitude to Mishkenot Sha'ananim and to Ms. Karin Moses for their organization of this Conference and for their accommodating hospitality, and to Prof. Igor Primoratz of the Hebrew University for his thoughtful invitation to me to participate and for his almost inexhaustible patience in waiting for my paper.I should mention also the pleasure of being with so many distinguished scholars from Israel, Europe and America, some of them old comrades (or antagonists) in the work for social justice, all of them, I fear, the intellectual betters of someone who, like myself, is (as it were) a professional activist rather than a systematic thinker. I am honoured to be in their company.
Punishment and its Alternatives — A Comment
Authors: Sebba Leslie 
Published: February 2016

The papers presented in this last session of the Conference — by Marc Galanter and Richard Abel — tend towards a quasi-sociological perspective, emphasizing the limits of the applicability of the criminal law and its implementation, and drawing attention to alternative normative systems — whether extra-penal or extra-legal.The papers differ, however, in at least two important respects. The first difference is in tone and orientation. While Galanter is essentially pragmatic, Abel's perspective is radical. On this point it is interesting to observe that Abel's radical criticisms are directed primarily at the inadequacies of the law in the context of the protection of the weaker members of society. Until recently, the radical thrust was generally directed at the overuse of the law against the underprivileged. Recently conducted victim surveys have pointed to the victimization of the poor by offenders rather than as offenders, and this information clearly forms part of the backdrop to Abel's analysis.
Punishment: Civil Style
Authors: Galanter Marc 
Published: February 2016

Discussions of punishment and its role in modern societies often proceed as if punishment is co-extensive with the criminal justice system. Instead, I want to begin with the observation that a large part of punishment as a social institution is outside the criminal law — indeed much of it lies outside the legal system. To understand the working of punishment in our societies and what the law can do with it and about it requires that we examine the entire span of punishment, not just that part which epitomizes it in legal theory.What is punishment? I hesitate to get into a definitional struggle on what must be well-worn turf. It seems to me that we can identify a core idea of “bad for bad” — i.e., the imposition of a harm, injury, deprivation or other bad thing on someone on the ground of the commission of some offence. The infliction of harm on the offender may be viewed as a goal (or as proximate to a goal of justice) or it may be viewed instrumentally as a means to social betterment, through rehabilitation, incapacitation, deterrence, reassurance, and so forth. Thus, the harm may be thought to redound to the offender's ultimate benefit or that of the society.
Ocular pathological changes in hamsters experimentally infected withSchistosoma mansoni
Authors: Ismail H.I.H. , Ashour D.S. , Abou Rayia D.M. , Ali A.L. 
Published: February 2016

AbstractOcular lesions have been reported in patients with schistosomiasis; however, the problem with studying schistosomal infection of the human eye is that biopsies are almost impossible to take, and histopathological examination of suspicious lesions can only be undertaken post-mortem or after enucleation. This work aimed to study the possible effects and pathogenesis of schistosomiasis on the eye. This study involved 55 hamsters; five hamsters remained non-infected and the remaining 50 hamsters were infected withSchistosoma mansonicercariae. Infected hamsters were sacrificed on weeks 8, 12, 16 and 20 post-infection (pi). Eye sections were prepared and stained for histopathological and immunohistochemical studies. Histopathological changes detected in hamsters infected after 16 and 20 weeks included looseness and oedema of the innermost retinal layers together with hyperplastic polypoid growth. Neither eggs nor granulomata were detected in eye sections throughout the experimental period. Deposition ofS. mansoniantigen was revealed in 35% of infected hamsters. Later, on weeks 16 and 20 pi, moderate subepithelial conjuctival deposits and marked subchoroidal and scleral deposition were detected. In conclusion, the deposition of schistosomal antigen and immune complexes may play a pivotal role in the ocular changes that occur in schistosomiasis, even in the absence of detectableSchistosomaeggs. Schistosomiasis should be suspected in cases with unexplained ophthalmological findings, especially in endemic areas.