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https://www.readbyqxmd.com/read/29399414/virus-like-particle-display-of-her2-induces-potent-anti-cancer-responses
#1
Arianna Palladini, Susan Thrane, Christoph M Janitzek, Jessica Pihl, Stine B Clemmensen, Willem Adriaan de Jongh, Thomas M Clausen, Giordano Nicoletti, Lorena Landuzzi, Manuel L Penichet, Tania Balboni, Marianna L Ianzano, Veronica Giusti, Thor G Theander, Morten A Nielsen, Ali Salanti, Pier-Luigi Lollini, Patrizia Nanni, Adam F Sander
Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms. Using a novel virus-like particle (VLP) based vaccine platform we show that directional, high-density display of human HER2 on the surface of VLPs, allows induction of therapeutically potent anti-HER2 autoantibody responses...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29378797/clinical-outcomes-of-submicroscopic-infections-and-correlates-of-protection-of-var2csa-antibodies-in-a-longitudinal-study-of-pregnant-women-in-colombia
#2
Kenneth Gavina, Sedami Gnidehou, Eliana Arango, Chloe Hamel-Martineau, Catherine Mitran, Olga Agudelo, Carolina Lopez, Aisha Karidio, Shanna Banman, Jaime Carmona-Fonseca, Ali Salanti, Nicaise Ndam, Michael Hawkes, Amanda Maestre, Stephanie K Yanow
BACKGROUND: Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium (P.) falciparum and P. vivax co-circulate. METHODS: A cohort of 187 pregnant women living in Puerto Libertador in Northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, RT-qPCR, and placental histopathology...
January 29, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29368665/dismantling-cognitive-behaviour-therapy-for-panic-disorder-a-systematic-review-and-component-network-meta-analysis
#3
Alessandro Pompoli, Toshi A Furukawa, Orestis Efthimiou, Hissei Imai, Aran Tajika, Georgia Salanti
Cognitive-behaviour therapy (CBT) for panic disorder may consist of different combinations of several therapeutic components such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure and/or in vivo exposure. It is therefore important both theoretically and clinically to examine whether specific components of CBT or their combinations are superior to others in the treatment of panic disorder. Component network meta-analysis (NMA) is an extension of standard NMA that can be used to disentangle the treatment effects of different components included in composite interventions...
January 25, 2018: Psychological Medicine
https://www.readbyqxmd.com/read/29330216/is-placebo-response-in-antidepressant-trials-rising-or-not-a-reanalysis-of-datasets-to-conclude-this-long-lasting-controversy
#4
REVIEW
Toshi A Furukawa, Andrea Cipriani, Stefan Leucht, Lauren Z Atkinson, Yusuke Ogawa, Nozomi Takeshima, Yu Hayasaka, Anna Chaimani, Georgia Salanti
It had long been believed that placebo response rates in antidepressant trials have been increasing and that they were responsible for rising numbers of so-called failed antidepressant trials. Two recent systematic reviews examined this issue and reached completely opposite findings. Furukawa and colleagues in a paper published in 2016 found that the placebo response rates are stable since 1991 and the apparent increase up to 2000 was confounded by changes in trial design features. By contrast, Khan and colleagues more recently concluded that placebo response rates had grown steadily in the past 30 years...
February 2018: Evidence-based Mental Health
https://www.readbyqxmd.com/read/29289944/causal-inference-from-experiment-and-observation
#5
Marcel Zwahlen, Geogia Salanti
Results from well-conducted randomised controlled studies should ideally inform on the comparative merits of treatment choices for a health condition. In the absence of this, one attempts to use evidence from the impact of treatment when administered according to decisions of the physicians and the patients (observational evidence). Naïve comparisons between treatment options using observational evidence will lead to biased results. Under certain conditions, however, it is possible to obtain valid estimates of the comparative merits of different treatments from observational data...
February 2018: Evidence-based Mental Health
https://www.readbyqxmd.com/read/29233084/a-model-for-meta-analysis-of-correlated-binary-outcomes-the-case-of-split-body-interventions
#6
Orestis Efthimiou, Dimitris Mavridis, Adriani Nikolakopoulou, Gerta Rücker, Sven Trelle, Matthias Egger, Georgia Salanti
In several areas of clinical research, it is common for trials to assign different sites of the participants' bodies to different interventions. For example, a randomized controlled trial comparing surgical techniques for correcting myopia may randomize each eye of a participant to a different operation. Under such bilateral ('split-body') interventions, the observations from each participant are correlated. It is challenging to account for these correlations at the meta-analysis level, especially when the outcome is rare...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/29089635/a-versatile-high-through-put-bead-based-phagocytosis-assay-for-plasmodium-falciparum
#7
Yukie M Lloyd, Elise P Ngati, Ali Salanti, Rose G F Leke, Diane W Taylor
Antibody-mediated phagocytosis is an important immune effector mechanism against Plasmodium falciparum-infected erythrocytes (IE); however, current phagocytosis assays use IE collected from infected individuals or from in vitro cultures of P. falciparum, making them prone to high variation. A simple, high-throughput flow cytometric assay was developed that uses THP-1 cells and fluorescent beads covalently-coupled with the malarial antigen VAR2CSA. The assay is highly repeatable, provides both the overall percent phagocytosis and semi-quantitates the number of antigen-coupled beads internalized...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29064911/efficacy-of-antidepressants-over-placebo-is-similar-in-two-armed-versus-three-armed-or-more-armed-randomized-placebo-controlled-trials
#8
Yusuke Ogawa, Toshi A Furukawa, Nozomi Takeshima, Yu Hayasaka, Lauren Z Atkinson, Shiro Tanaka, Andrea Cipriani, Georgia Salanti
Previous studies have reported that effect sizes of antidepressants were larger in two-armed than in three-armed or more-armed (multiarmed) randomized trials, where the probability of being allocated to placebo is lower. However, these studies have not taken into account the publication bias, differences among antidepressants, or covariance in multiarmed studies, or examined sponsorship bias. We searched published and unpublished randomized-controlled trials that compared placebo with 21 antidepressants for the acute treatment of major depression in adults...
October 23, 2017: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29062332/a-var2csa-csp-conjugate-capable-of-inducing-dual-specificity-antibody-responses
#9
Matondo Sungwa, Thrane Susan, Janitzek Christoph Mikkel, Kavishe Reginald Adolph, Mwakalinga Steven Boniface, Theander Thor Grundtvig, Salanti Ali, Nielsen Morten Agertoug, Sander Adam Frederik
BACKGROUND: Vaccine antigens targeting specific P. falciparum parasite stages are under pre-clinical and clinical development. It seems plausible that vaccine with multiple specificities will offer higher protection. With this hypothesis, we exploited the Spy-Tag/SpyCatcher conjugation system to make a, post expression, dual antigen conjugate vaccine, comprising two clinically tested antigen candidates (CSP and VAR2CSA). METHODS: The DBL1x-DBL2x-ID2a region of VAR2CSA was genetically fused with SpyTag at N-terminus...
June 2017: African Health Sciences
https://www.readbyqxmd.com/read/29029247/plasmodium-falciparum-infection-early-in-pregnancy-has-profound-consequences-for-foetal-growth
#10
Christentze Schmiegelow, Sungwa Matondo, Daniel T R Minja, Mafalda Resende, Caroline Pehrson, Birgitte Bruun Nielsen, Raimos Olomi, Morten A Nielsen, Philippe Deloron, Ali Salanti, John Lusingu, Thor G Theander
Malaria during pregnancy constitutes a large health problem in endemic areas. WHO recommends that interventions are initiated at the first antenatal visit, and these improve pregnancy outcomes. This study evaluated foetal growth by ultrasound and birth outcomes in women who were infected prior to the first antenatal visit (gestational age, GA<120 days) and not later in pregnancy. Compared to uninfected controls, women with early P. falciparum exposure had retarded intrauterine growth between a GA of 212 and 253 days (mean weight gain reduction: 107g [26;188], P=0...
October 6, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28962616/statistical-prediction-of-immunity-to-placental-malaria-based-on-multi-assay-antibody-data-for-malarial-antigens
#11
Chathura Siriwardhana, Rui Fang, Ali Salanti, Rose G F Leke, Naveen Bobbili, Diane Wallace Taylor, John J Chen
BACKGROUND: Plasmodium falciparum infections are especially severe in pregnant women because infected erythrocytes (IE) express VAR2CSA, a ligand that binds to placental trophoblasts, causing IE to accumulate in the placenta. Resulting inflammation and pathology increases a woman's risk of anemia, miscarriage, premature deliveries, and having low birthweight (LBW) babies. Antibodies (Ab) to VAR2CSA reduce placental parasitaemia and improve pregnancy outcomes. Currently, no single assay is able to predict if a woman has adequate immunity to prevent placental malaria (PM)...
September 29, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28912004/living-systematic-reviews-3-statistical-methods-for-updating-meta-analyses
#12
Mark Simmonds, Georgia Salanti, Joanne McKenzie, Julian Elliott
A living systematic review (LSR) should keep the review current as new research evidence emerges. Any meta-analyses included in the review will also need updating as new material is identified. If the aim of the review is solely to present the best current evidence standard meta-analysis may be sufficient, provided reviewers are aware that results may change at later updates. If the review is used in a decision-making context, more caution may be needed. When using standard meta-analysis methods, the chance of incorrectly concluding that any updated meta-analysis is statistically significant when there is no effect (the type I error) increases rapidly as more updates are performed...
November 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28912002/living-systematic-review-1-introduction-the-why-what-when-and-how
#13
REVIEW
Julian H Elliott, Anneliese Synnot, Tari Turner, Mark Simmonds, Elie A Akl, Steve McDonald, Georgia Salanti, Joerg Meerpohl, Harriet MacLehose, John Hilton, David Tovey, Ian Shemilt, James Thomas
Systematic reviews are difficult to keep up to date, but failure to do so leads to a decay in review currency, accuracy, and utility. We are developing a novel approach to systematic review updating termed "Living systematic review" (LSR): systematic reviews that are continually updated, incorporating relevant new evidence as it becomes available. LSRs may be particularly important in fields where research evidence is emerging rapidly, current evidence is uncertain, and new research may change policy or practice decisions...
September 11, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28903924/multivariate-and-network-meta-analysis-of-multiple-outcomes-and-multiple-treatments-rationale-concepts-and-examples
#14
Richard D Riley, Dan Jackson, Georgia Salanti, Danielle L Burke, Malcolm Price, Jamie Kirkham, Ian R White
No abstract text is available yet for this article.
September 13, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28739577/common-pitfalls-and-mistakes-in-the-set-up-analysis-and-interpretation-of-results-in-network-meta-analysis-what-clinicians-should-look-for-in-a-published-article
#15
Anna Chaimani, Georgia Salanti, Stefan Leucht, John R Geddes, Andrea Cipriani
OBJECTIVE: Several tools have been developed to evaluate the extent to which the findings from a network meta-analysis would be valid; however, applying these tools is a time-consuming task and often requires specific expertise. Clinicians have little time for critical appraisal, and they need to understand the key elements that help them select network meta-analyses that deserve further attention, optimising time and resources. This paper is aimed at providing a practical framework to assess the methodological robustness and reliability of results from network meta-analysis...
July 24, 2017: Evidence-based Mental Health
https://www.readbyqxmd.com/read/28646922/an-investigation-of-the-impact-of-using-different-methods-for-network-meta-analysis-a-protocol-for-an-empirical-evaluation
#16
Amalia Emily Karahalios, Georgia Salanti, Simon L Turner, G Peter Herbison, Ian R White, Areti Angeliki Veroniki, Adriani Nikolakopoulou, Joanne E Mckenzie
BACKGROUND: Network meta-analysis, a method to synthesise evidence from multiple treatments, has increased in popularity in the past decade. Two broad approaches are available to synthesise data across networks, namely, arm- and contrast-synthesis models, with a range of models that can be fitted within each. There has been recent debate about the validity of the arm-synthesis models, but to date, there has been limited empirical evaluation comparing results using the methods applied to a large number of networks...
June 24, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28578824/improving-the-malaria-transmission-blocking-activity-of-a-plasmodium-falciparum-48-45-based-vaccine-antigen-by-spytag-spycatcher-mediated-virus-like-display
#17
Susheel K Singh, Susan Thrane, Christoph M Janitzek, Morten A Nielsen, Thor G Theander, Michael Theisen, Ali Salanti, Adam F Sander
Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However, it remains essential to identify an optimal vaccine formulation that can facilitate induction of a long-lasting TB anti-Pfs48/45 response. Here we report on the development and evaluation of two Pfs48/45-based virus-like particle (VLP) vaccines generated using the AP205 SpyTag/Catcher VLP system...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28548690/rainbow-trout-oncorhynchus-mykiss-immune-response-towards-a-recombinant-vaccine-targeting-the-parasitic-ciliate-ichthyophthirius-multifiliis
#18
L von Gersdorff Jørgensen, P W Kania, K J Rasmussen, A H Mattsson, J Schmidt, A Al-Jubury, A Sander, A Salanti, K Buchmann
The protective effect in rainbow trout (Oncorhynchus mykiss) of an experimental subunit vaccine targeting antigens in the parasite Ichthyophthirius multifiliis has been evaluated and compared to effects elicited by a classical parasite homogenate vaccine. Three recombinant parasite proteins (two produced in E. coli and one in insect cells) were combined and injected i.p., and subsequently, protection and antibody responses were analysed. Both the experimental and the benchmark vaccine induced partial but significant protection against I...
May 26, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28541090/sixty-years-of-placebo-controlled-antipsychotic-drug-trials-in-acute-schizophrenia-systematic-review-bayesian-meta-analysis-and-meta-regression-of-efficacy-predictors
#19
REVIEW
Stefan Leucht, Claudia Leucht, Maximilian Huhn, Anna Chaimani, Dimitris Mavridis, Bartosz Helfer, Myrto Samara, Matteo Rabaioli, Susanne Bächer, Andrea Cipriani, John R Geddes, Georgia Salanti, John M Davis
OBJECTIVE: Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. METHOD: The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects...
October 1, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28527688/clinical-development-of-a-var2csa-based-placental-malaria-vaccine-pamvac-quantifying-vaccine-antigen-specific-memory-b-t-cell-activity-in-beninese-primigravidae
#20
Komi Gbédandé, Nadine Fievet, Firmine Viwami, Sem Ezinmegnon, Saadou Issifou, Jean-Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise Ndam, Willem Adriaan de Jongh, T Max M Søgaard, Ali Salanti, Morten A Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J F Luty
BACKGROUND: The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond...
May 17, 2017: Vaccine
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