EpiToolKit—a web server for computational immunomics

Predicting the T-cell-mediated immune response is an important task in vaccine design and thus one of the key problems in computational immunomics. Various methods have been developed during the last decade and are available online. We present EpiToolKit, a web server that has been specifically designed to offer a problem-solving environment for computational immunomics. EpiToolKit offers a variety of different prediction methods for major histocompatibility complex class I and II ligands as well as minor histocompatibility antigens. These predictions are embedded in a user-friendly interface allowing refining, editing and constraining the searches conveniently. We illustrate the value of the approach with a set of novel tumor-associated peptides. EpiToolKit is available online at www.epitoolkit.org

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

MEMORANDUMIntegrated conclusions of the International expert meeting held in Asolo

The papers presented at the symposium “Conservare il digitale”, held in Asolo on September 29, 2006, demonstrate the need for further reflection, the results of which will be submitted to national and international authorities and to the institutions and organizations involved in digital preservation. This reflection must start from some points of principle that all experts attending this international event share. They are expressed in the following agreed upon statements

Experiences of family caregivers 3-months after stroke: results of the prospective trans-regional network for stroke intervention with telemedicine registry (TRANSIT-Stroke)

Background Long-term support of stroke patients living at home is often delivered by family caregivers (FC). We identified characteristics of stroke patients being associated with receiving care by a FC 3-months (3 M) after stroke, assessed positive and negative experiences and individual burden of FC caring for stroke patients and determined factors associated with caregiving experiences and burden of FC 3 M after stroke. Methods Data were collected within TRANSIT-Stroke, a regional telemedical stroke-network comprising 12 hospitals in Germany. Patients with stroke/TIA providing informed consent were followed up 3 M after the index event. The postal patient-questionnaire was accompanied by an anonymous questionnaire for FC comprising information on positive and negative experiences of FC as well as on burden of caregiving operationalized by the Caregiver Reaction Assessment and a self-rated burden-scale, respectively. Multivariable logistic and linear regression analyses were performed. Results Between 01/2016 and 06/2019, 3532 patients provided baseline and 3 M-follow-up- data and 1044 FC responded to questionnaires regarding positive and negative caregiving experiences and caregiving burden. 74.4% of FC were older than 55 years, 70.1% were women and 67.5% were spouses. Older age, diabetes and lower Barthel-Index in patients were significantly associated with a higher probability of receiving care by a FC at 3 M. Positive experiences of FC comprised the importance (81.5%) and the privilege (70.0%) of caring for their relative; negative experiences of FC included financial difficulties associated with caregiving (20.4%). Median overall self-rated burden was 30 (IQR: 0–50; range 0–100). Older age of stroke patients was associated with a lower caregiver burden, whereas younger age of FC led to higher burden. More than half of the stroke patients in whom a FC questionnaire was completed did self-report that they are not being cared by a FC. This stroke patient group tended to be younger, more often male with less severe stroke and less comorbidities who lived more often with a partner. Conclusions The majority of caregivers wanted to care for their relatives but experienced burden at the same time. Elderly patients, patients with a lower Barthel Index at discharge and diabetes are at higher risk of needing care by a family caregiver. Trial registration The study was registered at “German Clinical Trial Register”: DRKS00011696. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS0001169

Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression

Immune-mediated effector molecules can limit cancer growth, but lack of sustained immune activation in the tumour microenvironment restricts antitumour immunity. New therapeutic approaches that induce a strong and prolonged immune activation would represent a major immunotherapeutic advance. Here we show that the arenaviruses lymphocytic choriomeningitis virus (LCMV) and the clinically used Junin virus vaccine (Candid# 1) preferentially replicate in tumour cells in a variety of murine and human cancer models. Viral replication leads to prolonged local immune activation, rapid regression of localized and metastatic cancers, and long-term disease control. Mechanistically, LCMV induces antitumour immunity, which depends on the recruitment of interferon-producing Ly6C(+) monocytes and additionally enhances tumour-specific CD8(+) T cells. In comparison with other clinically evaluated oncolytic viruses and to PD-1 blockade, LCMV treatment shows promising antitumoural benefits. In conclusion, therapeutically administered arenavirus replicates in cancer cells and induces tumour regression by enhancing local immune responses

Differential effects of methyl jasmonate on growth and division of etiolated zucchini cotyledons

Measurements of the jet energy calibration and transverse momentum resolution in CMS are presented, performed with a data sample collected in proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 36pb-1. The transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transverse momentum resolution. The results are presented for three different methods to reconstruct jets: a calorimeter-based approach, the "Jet-Plus-Track" approach, which improves the measurement of calorimeter jets by exploiting the associated tracks, and the "Particle Flow" approach, which attempts to reconstruct individually each particle in the event, prior to the jet clustering, based on information from all relevant subdetectors