Glycan analysis as biomarkers for testicular cancer

The U.S. Preventive Services Task Force does not recommend routine screening for testicular cancer (TC) in asymptomatic men, essentially because serological testicular cancer (TC) biomarkers are not reliable. The main reason is that two of the most important TC biomarkers, ?-fetoprotein (AFP) and human chorionic gonadotropin (hCG), are not produced solely due to TC. Moreover, up to 40% of patients with TC do not have elevated serological biomarkers, which is why serial imaging with CT is the chief means of monitoring progress. On the other hand, exposure to radiation can lead to an increased risk of secondary malignancies. This review provides the first comprehensive account of the applicability of protein glycoprofiling as a promising biomarker for TC with applications in disease diagnostics, monitoring and recurrence evaluation. The review first deals with the description and classification of TC. Secondly, the limitations of current TC biomarkers such as hCG, AFP and lactate dehydrogenase are provided together with an extensive overview of the glycosylation of hCG and AFP related to TC. The final part of the review summarises the potential of glycan changes on either hCG and AFP as TC biomarkers for diagnostics and prognostics purposes, and for disease recurrence evaluation. Finally, an analysis of glycans in serum and tissues as TC biomarkers is also provided. - 2019 by the authors.Funding: The authors wish to acknowledge the financial support received from the Slovak Research and Development Agency APVV 17-0300. This work was supported by the Ministry of Health of the Slovak Republic under project registration no. 2018/23-SAV-1. P.K. expresses thanks that this work was also made possible by NPRP grants NPRP 6-381-1-078 and NPRP-9-219-2-105 from the Qatar National Research Fund (A Member of The Qatar Foundation). The findings achieved herein are solely the responsibility of the authors.Scopu

Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states.

The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generate a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells, and develop a network-graph approach to examine the atlas at multiple spatial scales. We uncover highly connected promoter hubs that change substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merge to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. We identify widespread state-specific differences in enhancer activity and interactivity that correspond with an extensive reconfiguration of OCT4, SOX2 and NANOG binding and target gene expression. These findings provide multilayered insights into the chromatin-based gene regulatory control of human pluripotent states

Sharp and fuzzy observables on effect algebras

Observables on effect algebras and their fuzzy versions obtained by means of confidence measures (Markov kernels) are studied. It is shown that, on effect algebras with the (E)-property, given an observable and a confidence measure, there exists a fuzzy version of the observable. Ordering of observables according to their fuzzy properties is introduced, and some minimality conditions with respect to this ordering are found. Applications of some results of classical theory of experiments are considered.Comment: 23 page

Assessing the conservation value of waterbodies: the example of the Loire floodplain (France)

In recent decades, two of the main management tools used to stem biodiversity erosion have been biodiversity monitoring and the conservation of natural areas. However, socio-economic pressure means that it is not usually possible to preserve the entire landscape, and so the rational prioritisation of sites has become a crucial issue. In this context, and because floodplains are one of the most threatened ecosystems, we propose a statistical strategy for evaluating conservation value, and used it to prioritise 46 waterbodies in the Loire floodplain (France). We began by determining a synthetic conservation index of fish communities (Q) for each waterbody. This synthetic index includes a conservation status index, an origin index, a rarity index and a richness index. We divided the waterbodies into 6 clusters with distinct structures of the basic indices. One of these clusters, with high Q median value, indicated that 4 waterbodies are important for fish biodiversity conservation. Conversely, two clusters with low Q median values included 11 waterbodies where restoration is called for. The results picked out high connectivity levels and low abundance of aquatic vegetation as the two main environmental characteristics of waterbodies with high conservation value. In addition, assessing the biodiversity and conservation value of territories using our multi-index approach plus an a posteriori hierarchical classification methodology reveals two major interests: (i) a possible geographical extension and (ii) a multi-taxa adaptation

diverse human vh antibody fragments with bio therapeutic properties from the crescendo mouse

Abstract We describe the 'Crescendo Mouse', a human VH transgenic platform combining an engineered heavy chain locus with diverse human heavy chain V, D and J genes, a modified mouse Cγ1 gene and complete 3' regulatory region, in a triple knock-out (TKO) mouse background devoid of endogenous immunoglobulin expression. The addition of the engineered heavy chain locus to the TKO mouse restored B cell development, giving rise to functional B cells that responded to immunization with a diverse response that comprised entirely 'heavy chain only' antibodies. Heavy chain variable (VH) domain libraries were rapidly mined using phage display technology, yielding diverse high-affinity human VH that had undergone somatic hypermutation, lacked aggregation and showed enhanced expression in E. coli. The Crescendo Mouse produces human VH fragments, or Humabody® VH, with excellent bio-therapeutic potential, as exemplified here by the generation of antagonistic Humabody® VH specific for human IL17A and IL17RA

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy

\ua9 2022 The Authors. Purpose: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. Methods and Materials: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. Results: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients’ symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. Conclusions: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy

Metal Bioavailability in the Sava River Water

Metals present one of the major contamination problems for freshwater systems, such as the Sava River, due to their high toxicity, persistence, and tendency to accumulate in sediment and living organisms. The comprehensive assessment of the metal bioavailability in the Sava River encompassed the analyses of dissolved and DGT-labile metal species of nine metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) in the river water, as well as the evaluation of the accumulation of five metals (Cd, Cu, Fe, Mn, and Zn) in three organs (liver, gills, and gastrointestinal tissue) of the bioindicator organism, fish species European chub (Squalius cephalus L.).This survey was conducted mainly during the year 2006, in two sampling campaigns, in April/May and September, as periods representative for chub spawning and post-spawning. Additionally, metal concentrations were determined in the intestinal parasites acanthocephalans, which are known for their high affinity for metal accumulation. Metallothionein concentrations were also determined in three chub organs, as a commonly applied biomarker of metal exposure. Based on the metal concentrations in the river water, the Sava River was defined as weakly contaminated and mainly comparable with unpolluted rivers, which enabled the analyses of physiological variability of metal and metallothionein concentrations in the chub organs, as well as the establishment of their constitutive levels

Socially and biologically inspired computing for self-organizing communications networks

The design and development of future communications networks call for a careful examination of biological and social systems. New technological developments like self-driving cars, wireless sensor networks, drones swarm, Internet of Things, Big Data, and Blockchain are promoting an integration process that will bring together all those technologies in a large-scale heterogeneous network. Most of the challenges related to these new developments cannot be faced using traditional approaches, and require to explore novel paradigms for building computational mechanisms that allow us to deal with the emergent complexity of these new applications. In this article, we show that it is possible to use biologically and socially inspired computing for designing and implementing self-organizing communication systems. We argue that an abstract analysis of biological and social phenomena can be made to develop computational models that provide a suitable conceptual framework for building new networking technologies: biologically inspired computing for achieving efficient and scalable networking under uncertain environments; socially inspired computing for increasing the capacity of a system for solving problems through collective actions. We aim to enhance the state-of-the-art of these approaches and encourage other researchers to use these models in their future work

Pot, kettle: Nonliteral titles aren’t (natural) science

© 2020 The Author. Published by MIT Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1162/qss_a_00078Researchers may be tempted to attract attention through poetic titles for their publications, but would this be mistaken in some fields? Whilst poetic titles are known to be common in medicine, it is not clear whether the practice is widespread elsewhere. This article investigates the prevalence of poetic expressions in journal article titles 1996-2019 in 3.3 million articles from all 27 Scopus broad fields. Expressions were identified by manually checking all phrases with at least 5 words that occurred at least 25 times, finding 149 stock phrases, idioms, sayings, literary allusions, film names and song titles or lyrics. The expressions found are most common in the social sciences and the humanities. They are also relatively common in medicine, but almost absent from engineering and the natural and formal sciences. The differences may reflect the less hierarchical and more varied nature of the social sciences and humanities, where interesting titles may attract an audience. In engineering, natural science and formal science fields, authors should take extra care with poetic expressions, in case their choice is judged inappropriate. This includes interdisciplinary research overlapping these areas. Conversely, reviewers of interdisciplinary research involving the social sciences should be more tolerant of poetic licens