Findings of the Survey on Prevention of Plagiarism in Lithuanian Research Journals

AbstractAt the end of 2011, the Association of Lithuanian Serials initiated a survey, which aimed to ascertain whether Lithuanian journal editors, reviewers and authors encountered plagiarism, self-plagiarism and how they understood originality of a paper. Additionally, the survey looked at methods used for plagiarism prevention by editors and reviewers as well as ways, in which editors managed issues related to plagiarism. The survey suggests that no unanimous decision exists regarding the originality of a manuscript and that editors expect reviewers to identify plagiarism with little use of technologies. While answering to survey questions, respondents provided numerous comments. This demonstrates that plagiarism is a burning issue and scientific misconduct policy is needed in Lithuania. The survey was conducted during the period when the Lithuanian Research Council initiated the procedure for establishing the Ombudsman position. The Lithuanian Research Council funded several projects in 2012 and 2013, the aim of which was to familiarise the Lithuanian academic community with plagiarism prevention technologies and ethical aspects in academic publishing. The projects administrated by the Association of Lithuanian Serials provide research journal publishers and researchers related to journal publishing with a possibility of using CrossCheck system and discussing editorial policies

BMJ Open

Introduction Neonatal sepsis outreaches all causes of neonatal mortality worldwide and remains a major societal burden in low and middle income countries. In addition to limited resources, endemic morbidities, such as malaria and prematurity, predispose neonates and infants to invasive infection by altering neonatal immune response to pathogens. Nevertheless, thoughtful epidemiological, diagnostic and immunological evaluation of neonatal sepsis and the impact of gestational malaria have never been performed. Methods and analysis A prospective longitudinal multicentre follow-up of 580 infants from birth to 3 months of age in urban and suburban Benin will be performed. At delivery, and every other week, all children will be examined and clinically evaluated for occurrence of sepsis. At delivery, cord blood systematic analysis of selected plasma and transcriptomic biomarkers (procalcitonin, interleukin (IL)-6, IL-10, IP10, CD74 and CX3CR1) associated with sepsis pathophysiology will be evaluated in all live births as well as during the follow-up, and when sepsis will be suspected. In addition, whole blood response to selected innate stimuli and extensive peripheral blood mononuclear cells phenotypic characterisation will be performed. Reference intervals specific to sub-Saharan neonates will be determined from this cohort and biomarkers performances for neonatal sepsis diagnosis and prognosis tested. Ethics and dissemination Ethical approval has been obtained from the Comité d’Ethique de la Recherche – Institut des Sciences Biomédicales Appliquées (CER-ISBA 85 - 5 April 2016, extended on 3 February 2017). Results will be disseminated through international presentations at scientific meetings and publications in peer-reviewed journals

Développement clinique d'un vaccin contre le paludisme associé à la grossesse : étude de la mémoire immunologique spécifique du candidat vaccin VAR2CSA

The aim of this work was to investigate the development of cellular immunological memory with specificity for a vaccine candidate targeting malaria during pregnancy. Two complementary studies (STOPPAM and PLACMALVAC) were implemented by different European and African consortia and the end result is the clinical development of pregnancy-associated malaria (PAM) vaccine. The STOPPAM project comprised a follow-up study of 1037 pregnant women and 222 of their children. We evaluated immunological and parasitological parameters during pregnancy in order to facilitate the identification of a PAM vaccine candidate. The PLACMALVAC project aimed to prepare the future clinical trial Phase II through a follow-up study conducted in a cohort of 50 primigravid women and also to perform a Phase I clinical trial with healthy adult volunteers. We started by investigating the impacts of PAM on the immunological responses of newborns of mothers in the STOPPAM cohort. Cytokine production in response to TLR stimulation was evaluated and ex vivo phenotyping of different subsets of lymphocytes and immune cells was performed. Our findings suggest that placental infection at delivery altered the neonatal innate and adaptive immune responses that may have consequences for the development of immune responses in infancy. Next we focused on the immunological memory aspects related to the VAR2CSA vaccine candidate for malaria during pregnancy. Two different studies were performed to evaluate : i) VAR2CSA-DBL5 domain-specific IFN-g-secreting T-cell frequencies and five cytokine responses quantified using flow cytometric techniques. The study was carried out in two subgroups of pregnant women early in pregnancy and at delivery. Our data showed that PBMC at delivery of mothers with a history of infection during pregnancy but who were uninfected at delivery displayed significantly increased production of IFN-g in response to both PHA and DBL-5 stimulation compared to uninfected women. ii) Memory B and T cell responses to the VAR2CSA sub-unit vaccine candidate (ID1-DBL2-ID2a) in a cohort of pregnant primigravid Beninese who were followed up throughout pregnancy. Mononuclear cells from peripheral blood collected on 4 occasions (first and fifth month of pregnancy, at delivery and 6 months post-delivery) were isolated and cryopreserved under liquid nitrogen. The concentrations of 6 cytokines produced in response to the vaccine antigen were quantified in supernatants of stimulated cells using cytometric bead array. The frequencies of vaccine antigen-specific antibody-secreting memory B cells were evaluated in the same cell samples using standard ELISPOT assays. We observed that the frequencies of memory B cells with specificity for the vaccine candidate increased as a function of gestational age (from the first month of pregnancy to delivery) and of infection with P. falciparum during pregnancy. The results suggest that the induction of the cellular immunological memory responses to VAR2CSA required for protection against PAM may occur during first pregnancies and requires contact with antigen arising from naturally-acquired infections during those pregnancies. All the work done in this thesis provides an understanding of the immunological mechanisms involved an increased susceptibility during childhood due to PAM and also the progressive induction of immune memory to the candidate VAR2CSA (ID1-DBL2-ID2a) vaccine for prevention of malaria during pregnancy.L'objectif général de ce travail était d'étudier des mécanismes immunologiques de la mise en place d'une mémoire spécifique et protectrice au candidat vaccin contre le paludisme associé à la grossesse (PAG). Deux projets complémentaires (STOPPAM et PLACMALVAC) ont été mis en place par des consortiums européens et africains en vue du développement d'un vaccin contre le PAG. Le projet STOPPAM est un suivi de cohortes de 1037 femmes enceintes et de 222 nouveau-nés avec comme objectif de caractériser les parasites de P. falciparum pour identifier un candidat vaccin contre le PAG et aussi d'étudier les conséquences du PAG sur la santé de la mère et du nouveau-né. L'objectif du projet PLACMALVAC est de réaliser un essai clinique de phase I chez des femmes volontaires saines et en parallèle préparer un essai clinique de phase II par une étude de faisabilité avec un suivi de cohorte de 50 femmes enceintes primigestes. Dans une première partie, nous avons étudié les conséquences du PAG sur les profils de réponses immunologiques des nouveau-nés de 0 à 12 mois. Deux études ont été ainsi réalisées chez les enfants issus des mères présentant différentes histoires palustres au cours de la grossesse et donc des contacts in utero avec des antigènes palustres à différents moments de la grossesse. Nous avons étudiés l'évolution de 0 à 12 mois : des réponses cytokiniques à des ligands de TLR ainsi que les fréquences des lymphocytes CD4, CD8, Treg, NK et NKT. Nos résultats montrent que ce sont les infections à l'accouchement qui pourraient modifier et altérer l'activation du système immunitaire inné et adaptative. Cette altération influencerait la mise en place d'une immunité protectrice chez les nouveau-nés pendant leurs premières années de vie. La deuxième partie de notre travail s'est intéressée à l'évaluation des réponses immunologiques des cellules T et B mémoires spécifiques du candidat vaccin VAR2CSA. Deux études ont été réalisées pour évaluer: i) les réponses des cellules T mémoires chez 2 sous groupes de femmes enceintes du projet STOPPAM prélevées au début de la grossesse et à l'accouchement. Nous avons caractérisé des réponses des cellules T mémoires spécifique du VAR2CSA-DBL5 via la fréquence des cellules T sécrétrices de l'IFN-g et la mesure de 5 cytokines dans les surnageants de culture après stimulation des cellules mononucléées. Nos résultats montrent que l'infection palustre au cours de la grossesse est associée à une plus forte production d'IFN-g à l'accouchement en réponse à la stimulation in vitro avec le VAR2CSA-DBL5 et la PHA. ii) les réponses des cellules T et B mémoires chez les primigestes du projet PLACMALVAC afin d'étudier la construction naturelle de la mémoire spécifique au VAR2CSA (ID1-DBL2-ID2a) durant la première grossesse. Les cellules mononucléées ont été isolées et congelées à partir des prélèvements du sang veineux collectés à 4 différents moments au cours du suivi (premier et cinquième mois de grossesse, à l'accouchement et 6 mois après accouchement). Nous avons quantifié les cellules B mémoires spécifiques de l'antigène vaccinal VAR2CSA et aussi mesuré les cytokines dans les surnageants de culture après stimulation des cellules. L'infection palustre au cours de la grossesse est associée à une augmentation de la fréquence des cellules B mémoires. Ces résultats suggèrent, l'acquisition via des infections naturelles au cours de la première grossesse, d'une mémoire anti-VAR2CSA protectrice pour la prévention du PAG. ? L'ensemble des travaux réalisés au cours de cette thèse a permis de mieux comprendre les mécanismes immunologiques impliqués dans la plus grande susceptibilité des nouveau-nés aux infections liées au PAG pendant l'enfance et aussi l'acquisition naturelle d'une mémoire immunologique contre le PAG spécifique du candidat vaccin actuel VAR2CSA (ID1-DBL2-ID2a) qui est en cours d'essai clinique de phase I au Bénin et en Allemagne

TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria

Abstract Background Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes. Methods The split-luciferase complementation assay (LCA) was used to investigate cell signaling mechanisms downstream of tumor necrosis factor receptor 1 (TNFR1) that could contribute to changes in neuronal excitability in eCM. Whole-cell patch-clamp electrophysiology was performed in brain slices from eCM mice to elucidate consequences of infection on CA1 pyramidal neuron excitability and cell signaling mechanisms that contribute to observed phenotypes. Involvement of identified signaling molecules in mediating behavioral changes and sickness behavior observed in eCM were investigated in vivo using genetic silencing. Results Exploring signaling mechanisms that underlie TNF-induced effects on neuronal excitability, we found that the complex assembly of fibroblast growth factor 14 (FGF14) and the voltage-gated Na+ (Nav) channel 1.6 (Nav1.6) is increased upon tumor necrosis factor receptor 1 (TNFR1) stimulation via Janus Kinase 2 (JAK2). On account of the dependency of hyperinflammatory experimental cerebral malaria (eCM) on TNF, we performed patch-clamp studies in slices from eCM mice and showed that Plasmodium chabaudi infection augments Nav1.6 channel conductance of CA1 pyramidal neurons through the TNFR1–JAK2–FGF14–Nav1.6 signaling network, which leads to hyperexcitability. Hyperexcitability of CA1 pyramidal neurons caused by infection was mitigated via an anti-TNF antibody and genetic silencing of FGF14 in CA1. Furthermore, knockdown of FGF14 in CA1 reduced sickness behavior caused by infection. Conclusions FGF14 may represent a therapeutic target for mitigating consequences of TNF-mediated neuroinflammation