The ‘KASCADE Cosmic ray Data Centre’ is a web portal (
https://kcdc.ikp.kit.edu
), where the data of the astroparticle physics experiment KASCADE-Grande are made available for the interested public. ...The KASCADE experiment was a large-area detector for the measurement of high-energy cosmic rays via the detection of extensive air showers. The multi-detector installations KASCADE and its extension KASCADE-Grande stopped the active data acquisition in 2013 after more than 20 years of data taking. In several updates since our first release in 2013 with KCDC we provide the public measured and reconstructed parameters of more than 433 million air showers. In addition, KCDC provides meta data information and documentation to enable a user outside the community of experts to perform their own data analysis. Simulation data from three different high energy interaction models have been made available as well as a compilation of measured and published spectra from various experiments. In addition, detailed educational examples shall encourage high-school students and early stage researchers to learn about astroparticle physics, cosmic radiation as well as the handling of Big Data and about the sustainable and public provision of scientific data.
To determine the contribution of herpes simplex type 2 (HSV-2) infection to the risk of human immunodeficiency virus (HIV) acquisition, a systematic review of literature and data synthesis were done. ...Thirty-one studies addressed the risk of HIV infection in HSV-2–seropositive persons. For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4–3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1–5.1), but the temporal sequence of the 2 infections cannot be documented. Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention
The optimal management of stage I follicular lymphoma, according to consensus guidelines, is based on uncontrolled experiences of select institutions. Diverse treatment approaches are used despite ...guidelines that recommend radiation therapy (XRT).
We analyzed outcomes of patients with stage I follicular lymphoma enrolled onto the National LymphoCare database.
Of 471 patients with stage I follicular lymphoma, 206 patients underwent rigorous staging as defined by both a bone marrow aspirate and biopsy and an imaging study (a computed tomography CT scan of the whole body, a positron emission tomography PET/CT scan, or both). Rigorously staged patients had superior progression-free survival (PFS) compared with nonrigorously staged patients (hazard ratio HR, 0.63). Treatments given to rigorously staged patients were rituximab/chemotherapy (R-chemo; 28%), XRT (27%), observation (17%), systemic therapy + XRT (13%), rituximab monotherapy (12%), and other (3%). With a median follow-up of 57 months for PFS, there were 44 progression events (in 21% of patients) for rigorously staged patients. For these patients, PFS was significantly improved with either R-chemo or systemic therapy + XRT compared with patients receiving XRT alone after adjustment for histology, LDH, and the presence of B symptoms. There were no differences in overall survival.
In this largest, prospectively enrolled group of patients with stage I follicular lymphoma, variable treatment approaches resulted in similar excellent outcomes, which challenges the paradigm that XRT should be standard for this presentation.
Summary
Background
Oligo‐astheno‐teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute ...to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options.
Materials and Methods
PubMed was searched for papers in English for articles with search terms: male infertility and oligo‐astheno‐teratozoospermia. For evidence‐based recommendations, the GRADE system was applied. Issues related to urogenital infections/inflammations have not been included in this document as they will be covered by separate guidelines.
Results
For men with oligo‐astheno‐teratozoospermia, the European Academy of Andrology recommends:
A general physical examination to assess signs of hypogonadism.
A scrotal physical examination to assess (i) the testes and epididymes for volume and consistency, (ii) deferent ducts for total or partial absence, and (iii) occurrence of varicocoele.
Performing two semen analyses, according to World Health Organization guidelines to define an oligo‐astheno‐teratozoospermia.
An endocrine evaluation.
A scrotal ultrasound as part of routine investigation.
Karyotype analysis and assessment of Yq microdeletions in infertile men with a sperm concentration ≤5 × 106/mL.
Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for incomplete congenital obstruction of the genital tract.
Against quitting physical activity to improve the chance of achieving pregnancy.
Against androgen replacement therapy to improve the chance of achieving pregnancy.
Assisted reproduction techniques to improve the chance of achieving pregnancy, in case other treatment options are not available or not efficient.
Androgen replacement therapy in patients with biochemical/clinical signs of hypogonadism, after completion of the fertility treatment.
Conclusion
These guidelines can be applied in clinical work and indicate future research needs.
We examined the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the United States and confirmed our ...results in an independent cohort of patients from France.
Patients with newly diagnosed DLBCL and treated with anthracycline-based immunochemotherapy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence and the Léon Bérard Cancer Center, Lyon, France. In those with relapse, details at relapse and outcomes were abstracted from records.
680 individuals with DLBCL were identified from the MER, 552 (81%) of whom achieved remission after induction. 112 of the 552 patients (20%) suffered a relapse. The majority (64%) of relapses were identified before a scheduled follow-up visit. Surveillance imaging detected DLBCL relapse before clinical manifestations in nine out of 552 patients (1.6%) observed after therapy. In the Lyon cohort, imaging identified asymptomatic DLBCL relapse in four out of 222 patients (1.8%). There was no difference in survival after DLBCL relapse in patients detected at scheduled follow-up versus before scheduled follow-up in both the MER (P = .56) and Lyon cohorts (P = .25).
The majority of DLBCL relapses are detected outside of planned follow-up, with no difference in outcome in patients with DLBCL detected at a scheduled visit compared with patients with relapse detected outside of planned follow-up. These data do not support the use of routine surveillance imaging for follow-up of DLBCL.
Optimal therapy of follicular lymphoma (FL) is not defined. We analyzed a large prospective cohort study to identify current demographics and patterns of care of FL in the United States.
The National ...LymphoCare Study is a multicenter, longitudinal, observational study designed to collect information on treatment regimens and outcomes for patients with newly diagnosed FL in the United States. Patients were enrolled between 2004 and 2007. There is no study-specific prescribed treatment regimen or intervention.
Two thousand seven hundred twenty-eight subjects were enrolled at 265 sites, including the 80% of patients enrolled from nonacademic sites. Using the Follicular Lymphoma International Prognostic Index (FLIPI), three distinct groups independent of histologic grade could be defined. Initial therapeutic strategy was: observation, 17.7%; rituximab monotherapy, 13.9%; clinical trial 6.1%; radiation therapy, 5.6%; chemotherapy only, 3.2%; chemotherapy plus rituximab, 51.9%. Chemotherapy plus rituximab regimens were: rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone, 55.0%; rituximab plus cyclophosphamide, vincristine, and prednisone, 23.1%; rituximab plus fludarabine based, 15.5%; other, 6.4%. The choice to initiate therapy rather than observe was associated with age, FLIPI, stage, and grade (P < .01). Significant differences in treatment (P < .01) across regions of the United States were noted. Contrary to practice guidelines, treatment of stage I FL frequently omits radiation therapy.
Widely disparate therapeutic approaches are utilized for FL. Initial therapy is deferred in a small subset of patients. There is no single standard of care for the treatment of de novo FL, although antibody use is ubiquitous when therapy is initiated. These disparate approaches to the initial care of patients with FL render a heterogeneous group of patients at relapse.
High-level microsatellite instability (MSI-H) has been reported as a prognostic marker in colon cancer. We here analysed the prognostic significance of MSI and mutations of the Beta2-Microglobulin ...(B2M) gene, which occur in about 30% of MSI-H colon cancer, in the cohort of the prospective FOGT-4 (Forschungsruppe Onkologie Gastrointestinale Tumoren, FOGT) trial.
Microsatellite instability status was determined using standard protocols (NCI/ICG-HNPCC panel and CAT25) in 223 colon cancer lesions. Beta2-Microglobulin mutation status was evaluated by exon-wise sequencing in all MSI-H lesions.
Patients with MSI-H (n=34) colon cancer presented with a significantly lower risk of relapse after 12 months of follow-up compared with MSS (n=189) colon cancer patients (5 year time to relapse: MSI-H 0.82 vs MSS 0.66, P=0.03). No significant difference in overall survival was detected. Beta2-Microglobulin mutations were identified in 10 (29.4%) out of 34 MSI-H colon cancers and were associated with a complete absence of disease relapse or tumour-related death events (P=0.09).
The risk of late disease relapse was significantly lower in patients with MSI-H compared with MSS colon cancer. Moreover, B2M mutations may contribute to the favourable outcome of MSI-H colon cancer patients and should therefore be evaluated as a potential prognostic marker in future clinical trials.
In the last two decades, remarkable advances have been made in the development of technologies used to engineer new aptamers and ribozymes. This has encouraged interest among researchers who seek to ...create new types of gene-control systems that can be made to respond specifically to small-molecule signals. Validation of the fact that RNA molecules can exhibit the characteristics needed to serve as precision genetic switches has come from the discovery of numerous classes of natural ligand-sensing RNAs called riboswitches. Although a great deal of progress has been made toward engineering useful designer riboswitches, considerable advances are needed before the performance characteristics of these RNAs match those of protein systems that have been co-opted to regulate gene expression. In this review, we will evaluate the potential for engineered RNAs to regulate gene expression and lay out possible paths to designer riboswitches based on currently available technologies. Furthermore, we will discuss some technical advances that would empower RNA engineers who seek to make routine the production of designer riboswitches that can function in eukaryotes.
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