XIth EPR Workshop on Applications of EPR in Biology and Medicine.

We are pleased and honored to present this special issue for CBBI on the broad topic of biomedical EPR. The papers herein resulted from the most recent October 2019 EPR Workshop in Kraków that encompasses work from outstanding researchers in the field. Before describing the range of articles, we have briefly summarized the history of these workshops and the publications that resulted.

Frontiers in Molecular Evolutionary Medicine.

This paper surveys some of the important insights that molecular evolution has contributed to evolutionary medicine; they include phage therapy, cancer biology, helminth manipulation of the host immune system, quality control of gametes, and pathogen outbreaks. Molecular evolution has helped to revolutionize our understanding of cancer, of autoimmune disease, and of the origin, spread, and pathogenesis of emerging diseases, where it has suggested new therapies, illuminated mechanisms, and revealed historical processes: all have practical therapeutic implications. While much has been accomplished, much remains to be done.

Tracking tumor biology with radiomics: A systematic review utilizing a radiomics quality score.

INTRODUCTION: In this review we describe recent developments in the field of radiomics along with current relevant literature linking it to tumor biology. We furthermore explore the methodologic quality of these studies with our in-house radiomics quality scoring (RQS) tool. Finally, we offer our vision on necessary future steps for the development of stable radiomic features and their links to tumor biology. METHODS: Two authors (S.S. and H.W.) independently performed a thorough systematic literature search and outcome extraction to identify relevant studies published in MEDLINE/PubMed (National Center for Biotechnology Information, NCBI), EMBASE (Ovid) and Web of Science (WoS). Two authors (S.S, H.W) separately and two authors (J.v.T and E.d.J) concordantly scored the articles for their methodology and analyses according to the previously published radiomics quality score (RQS). RESULTS: In summary, a total of 655 records were identified till 25-09-2017 based on the previously specified search terms, from which n = 236 in MEDLINE/PubMed, n = 215 in EMBASE and n = 204 from Web of Science. After determining full article availability and reading the available articles, a total of n = 41 studies were included in the systematic review. The RQS scoring resulted in some discrepancies between the reviewers, e.g. reviewer H.W scored 4 studies ≥50%, reviewer S.S scored 3 studies ≥50% while reviewers J.v.T and E.d.J scored 1 study ≥50%. Up to nine studies were given a quality score of 0%. The majority of studies were scored below 50%. DISCUSSION: In this study, we performed a systematic literature search linking radiomics to tumor biology. All but two studies (n = 39) revealed that radiomic features derived from ultrasound, CT, PET and/or MR are significantly associated with one or several specific tumor biologic substrates, from somatic mutation status to tumor histopathologic grading and metabolism. Considerable inter-observer differences were found with regard to RQS scoring, while important questions were raised concerning the interpretability of the outcome of such scores.

Usos de referências biológicas em publicações de Saúde Mental Global / Uses of biological references in publications related to Global Mental Health

Resumo Desde sua emergência em 2007, o campo da Saúde Mental Global se depara com críticas que costumam advir das Ciências Sociais e Psiquiatria Transcultural. Um ponto criticado, que se supõe caracterizar o campo, é sua tendência a se pautar em explicações biológicas para problemas de saúde mental, que teriam assim quaisquer outras dimensões relegadas a segundo plano. A fim de analisar o quanto o movimento do Global Mental Health se baseia em explicações biológicas de transtornos mentais, no período de 2014 foi realizada uma pesquisa cruzando expressões ligadas à biologia e a de “global mental health” na base de dados PubMed, além de publicações mais recentes associadas ao movimento. No presente artigo, são apresentadas as conclusões sobre a incorporação de referências biológicas em textos recentes associados ao campo da Saúde Mental Global. Embora haja poucos textos com referências diretas à biologia, nota-se que elas parecem ocorrer para justificar a necessidade de políticas de saúde mental.

Abstract Since its emergence in 2007, the field of Global Mental Health has faced constant criticism by Transcultural Psychiatry and the Social Sciences. A main issue is the field's supposed tendency to make use of biological explanations so as to explain mental disorders, which would then have any other dimensions relegated to background. In order to analyze to what extent Global Mental Health relies on biological explanations, we searched during July of 2014 for expressions related to biology and “global mental health” in PubMed database and in recent publications associated with the field. In this article we present some conclusions about the incorporation of biological references in recent publications associated with Global Mental Health. Although there are very few explicit biological references in those texts, they seem to be used in order to justify the need for mental health policy. We also make some remarks about a context-specific view of biology.

Biological causal links on physiological and evolutionary time scales.

Correlation does not imply causation. If two variables, say A and B, are correlated, it could be because A causes B, or that B causes A, or because a third factor affects them both. We suggest that in many cases in biology, the causal link might be bi-directional: A causes B through a fast-acting physiological process, while B causes A through a slowly accumulating evolutionary process. Furthermore, many trained biologists tend to consistently focus at first on the fast-acting direction, and overlook the slower process in the opposite direction. We analyse several examples from modern biology that demonstrate this bias (codon usage optimality and gene expression, gene duplication and genetic dispensability, stem cell division and cancer risk, and the microbiome and host metabolism) and also discuss an example from linguistics. These examples demonstrate mutual effects between the fast physiological processes and the slow evolutionary ones. We believe that building awareness of inference biases among biologists who tend to prefer one causal direction over another could improve scientific reasoning.

In vivo crystallography at X-ray free-electron lasers: the next generation of structural biology?

The serendipitous discovery of the spontaneous growth of protein crystals inside cells has opened the field of crystallography to chemically unmodified samples directly available from their natural environment. On the one hand, through in vivo crystallography, protocols for protein crystal preparation can be highly simplified, although the technique suffers from difficulties in sampling, particularly in the extraction of the crystals from the cells partly due to their small sizes. On the other hand, the extremely intense X-ray pulses emerging from X-ray free-electron laser (XFEL) sources, along with the appearance of serial femtosecond crystallography (SFX) is a milestone for radiation damage-free protein structural studies but requires micrometre-size crystals. The combination of SFX with in vivo crystallography has the potential to boost the applicability of these techniques, eventually bringing the field to the point where in vitro sample manipulations will no longer be required, and direct imaging of the crystals from within the cells will be achievable. To fully appreciate the diverse aspects of sample characterization, handling and analysis, SFX experiments at the Japanese SPring-8 angstrom compact free-electron laser were scheduled on various types of in vivo grown crystals. The first experiments have demonstrated the feasibility of the approach and suggest that future in vivo crystallography applications at XFELs will be another alternative to nano-crystallography.

Mitochondria in biology and medicine--2012.

As the understanding of mitochondria and their importance for the cell and organism is developing, increasing evidence is demonstrating the organelle to be intricately involved in an extensive range of pathologies. This range of pathologies include general signs of premature aging, neuro-muscular dysfunctions, cancer, diabetes, various heart diseases, inflammation and other conditions not previously known to be related to mitochondrial function. A better understanding of mitochondria therefore allows a better understanding of related pathologies. It enables the usage of mitochondrial function as biomarkers for the diseases and most important, it opens the possibility of a treatment or a cure for a disease. "Mitochondria in Biology and Medicine" was the title of the second annual conference of Society of Mitochondrial Research and Medicine-India. The conference was organized by Rana P. Singh, Keshav Singh and Kumarasamy Thangaraj, and was held at the newly opened School of Life Sciences, Central University of Gujarat (CUG), Gandhinagar, India, during 2-3 November 2012. The conference featured talks from internationally renowned scientists within the field of mitochondrial research and offered both students and fellow researchers a comprehensive update to the newest research within the field. This paper summarizes key outcomes of the presentations.

Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

Can we change the disease biology of multiple myeloma?

Despite improvements in disease management, multiple myeloma (MM) remains incurable. Conventional treatment methods are unsatisfactory, leading to a pattern of regression and remission, and ultimately failure. This pattern suggests that one of the possible strategies for improving outcomes is continuous therapy to maintain suppression of the surviving tumor cells. Optimal management of MM requires potent agents and modalities with direct tumoricidal activity, which can also provide continuous suppression of the residual tumor to prevent disease relapse. Immunomodulatory agents exert immunomodulatory and tumoricidal effects, and cause disruption of stromal cell support from the bone marrow microenvironment. Therefore continuous therapy with immunomodulatory agents may be able to provide both tumor reduction and tumor suppression, enabling physicians to consider the possibility of incorporating continuous therapy into the treatment paradigm of patients with MM.

'Hearts and bones': the ups and downs of 'plasticity' in stem cell biology.

More than a decade ago, 'plasticity' suddenly became a 'fashionable' topic with overemphasized implications for regenerative medicine. The concept of 'plasticity' is supported by old transplantation work, at least for embryonic cells, and metaplasia is a classic example of plasticity observed in patients. Nevertheless, the publication of a series of papers showing rare conversion of a given cell type into another unrelated cell raised the possibility of using any unaffected tissue to create at will new cells to replace a different failing tissue or organ. This resulted in disingenuous interpretations and a reason not to fund anymore research on embryonic stem cells (ESc). Moreover, many papers on plasticity were difficult to reproduce and thus questioned; raising issues about plasticity as a technical artefact or a consequence of rare spontaneous cells fusion. More recently, reprogramming adult differentiated cells to a pluripotent state (iPS) became possible, and later, one type of differentiated cell could be directly reprogrammed into another (e.g. fibroblasts into neurons) without reverting to pluripotency. Although the latter results from different and more robust experimental protocols, these phenomena also exemplify 'plasticity'. In this review, we want to place 'plasticity' in a historical perspective still taking into account ethical and political implications.

Ceramide synthases at the centre of sphingolipid metabolism and biology.

Sphingolipid metabolism in metazoan cells consists of a complex interconnected web of numerous enzymes, metabolites and modes of regulation. At the centre of sphingolipid metabolism reside CerSs (ceramide synthases), a group of enzymes that catalyse the formation of ceramides from sphingoid base and acyl-CoA substrates. From a metabolic perspective, these enzymes occupy a unique niche in that they simultaneously regulate de novo sphingolipid synthesis and the recycling of free sphingosine produced from the degradation of pre-formed sphingolipids (salvage pathway). Six mammalian CerSs (CerS1-CerS6) have been identified. Unique characteristics have been described for each of these enzymes, but perhaps the most notable is the ability of individual CerS isoforms to produce ceramides with characteristic acyl-chain distributions. Through this control of acyl-chain length and perhaps in a compartment-specific manner, CerSs appear to regulate multiple aspects of sphingolipid-mediated cell and organismal biology. In the present review, we discuss the function of CerSs as critical regulators of sphingolipid metabolism, highlight their unique characteristics and explore the emerging roles of CerSs in regulating programmed cell death, cancer and many other aspects of biology.