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SummaryTo inform immunotherapy approaches in children, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve pediatric nervous system tumours (pedNST) spanning 12 cancer types from three public data sets. Within pedNST, we uncovered four broad immune clusters: Pediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Excluded (17%). We validated these clusters using immunohistochemistry, methylation immune inference, and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune-cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters. Given the heterogeneity within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.

Summary The development of effective and safe COVID‐19 vaccines is a major move forward in our global effort to control the SARS‐CoV‐2 pandemic. The aims of this study were (1) to develop an inactivated whole‐virus SARS‐CoV‐2 candidate vaccine named BIV1‐CovIran and (2) to determine the safety and potency of BIV1‐CovIran inactivated vaccine candidate against SARS‐CoV‐2. Infectious virus was isolated from nasopharyngeal swab specimen and propagated in Vero cells with clear cytopathic effects in a biosafety level‐3 facility using the World Health Organization’s laboratory biosafety guidance related to COVID‐19. After characterisation of viral seed stocks, the virus working seed was scaled‐up in Vero cells. After chemical inactivation and purification, it was formulated with alum adjuvant. Finally, different animal species were used to determine the toxicity and immunogenicity of the vaccine candidate. The study showed the safety profile in studied animals including guinea pig, rabbit, mice and monkeys. Immunisation at two different doses (3 or 5 μg per dose) elicited a high level of SARS‐CoV‐2 specific and neutralising antibodies in mice, rabbits and nonhuman primates. Rhesus macaques were immunised with the two‐dose schedule of 5 or 3 μg of the BIV1‐CovIran vaccine and showed highly efficient protection against 104 TCID50 of SARS‐CoV‐2 intratracheal challenge compared with the control group. These results highlight the BIV1‐CovIran vaccine as a potential candidate to induce a strong and potent immune response that may be a promising and feasible vaccine to protect against SARS‐CoV‐2 infection.

This paper is aimed at discussing a series of energy sustainability solutions proposed by a master class of students in environmental engineering using analytical and visual collaborative tools. The activities described are part of the class “Sustainability and renewable sources” at the University of Modena and Reggio Emilia. Six groups of 3-4 students worked on six energy efficiency and sustainability projects chosen from a remote area of the Apennines in Emilia Romagna. The specificity of the case-study framework allowed the implementation of projects where different sustainability aspects are integrated using tools of transitional thinking: agro-food production, use of renewable energy sources, waste management and social integration were considered. Each group identified the key actors for each project, allowing them to approach sustainability from a multilevel perspective. Net Present Value analyses were applied to evaluate economic viability of each project. Photovoltaic power plants and boilers fueled with local wood are the main renewable energy source identified to promote energy sustainability in each project. As result, the combination of the six works creates a powerful tool to demonstrate possible best practices for remote mountain areas.

Prior to 1994, the media operated in an environment that can best be described as ‘suppressed’. Diversity of thoughts, views and opinions on media platforms were non-existent as the regime, at the time, ruled with an iron-fist. A variety of print media outlets sought to reflect reality, but it was a steady struggle especially for those with meagre resources, and exacerbated by the constant clampdowns. The state-run broadcaster, if anything, entrenched discriminatory principles and practices. Given our precarious past, the birth of democracy proved to be the perfect panacea for a promising pathway for the media fraternity. Transformation, in more ways than one, permeated the sector. Reflections of the South African Media: 1994-2019 is a compilation by authors who have peculiar insight of and excelled in the different areas of the fast-developing industry in the first 25 years of South Africa’s democracy. And they are no ordinary authors. Every chapter contributed came from women and men who had, through the years, a direct link with ML Sultan Technikon, Technikon Natal, Durban Institute of Technology (DIT) or Durban University of Technology (DUT) * either as a student, lecturer, visiting professor, speaker or associate. Compiling and editing this book has been an incredibly invigorating experience. It was never in doubt whose image will adorn the cover of the book, so it was beautifully uplifting that many authors, not knowing my choice, gave Nelson Mandela due recognition. My brief to the authors was simple: let me have your personal lookback in your own style on the topic that you are most comfortable with. All of them stepped up to the plate, and the vast array of content in the book bares strong testimony. A section titled Journeys in Journalism encapsulates input from alumni of DUT Journalism – they were afforded free reign to trace the territory they traversed. I’m indebted to each and every contributor for generously volunteering their precious time and talent to the book. They were simply magnificent. It has to be said that this publication far exceeded my expectations as it, initially, was a humble idea to celebrate 25 years of the media industry with a handful of contributions. Little did I realise that my desk will be flooded with 40 pieces of excellence and a Foreword penned by the brilliant Jeremy Thompson. My eternal gratitude must also be extended to the small team of assistants for understanding my vision upfront and rallying remarkably throughout. Once you’ve enjoyed the read, I invite you to share Reflections of the South African Media: 1994-2019 with whoever you believe can benefit from its rich and diverse content!

INTRODUCTION: Recent clinical trials of immune checkpoint inhibitors indicated 5-11% response rate in pediatric patients depending on cancer type and expression of target proteins. Currently, a systematic analysis characterizing the immune microenvironment of childhood tumors is lacking. The main objective of this study is to uncover the features of immune microenvironment in pediatric nervous system tumors (pedNST). METHODS: We compiled transcriptomes of 925 tumors from three initiatives, Therapeutically Applicable Research To Generate Effective Treatments (TARGET, n = 149), International Cancer Genome Consortium (ICGC, n = 195) and Children Brain Tumor Tissue Network (CBTN, n = 581). We analyzed the performance of immune deconvolution tools and used publicly available datasets to define immune genesets. We conducted a consensus analysis to assign genes to cell-types and identify immunological groups. RESULTS: We found wide variability in immune infiltration across and within cancer types ranging from cold tumors such as medulloblastoma (2.7% infiltrate) to infiltrated entities such as neurofibroma (22.6%). Consensus clustering revealed four distinct immune clusters. The pediatric inflamed group (10%) included MYCN non-amplified neuroblastoma and ATRT. The myeloid-predominant group (30%) showed decreased infiltration of lymphoid cells but enrichment of myeloid cell genesets. The pediatric-cold group (42%) harbored no enrichment of immune genesets and included 72% of ependymomas and 65% of medulloblastomas. The immune excluded group (18%) showed depletion of immune cell-types and included sonic-hedgehog medulloblastoma. 71% of pedNST belonged to the lymphocyte depleted or immunologically quiet clusters, indicating the cold immune microenvironment in pedNST compared to adult cancers. CONCLUSION: We report characteristics of the immune microenvironment in pedNST. We found an overall cold microenvironment with low lymphocyte infiltration in this population compared to common adult cancers. We identified ~10% of tumors harboring a relatively inflamed microenvironment. Our data uncover characteristics of immune infiltration in pediatric tumors with potential implications to guide therapy.

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy., Hypermutation and microsatellite burden determine responses and long-term survival following PD-1 blockade in children and young adults with refractory cancers resulting from germline DNA replication repair deficiency.

Background Programmed death-ligand 1 (PD-L1), also called B7 homolog 1 (B7-H1), is a human protein playing an important biomarker role in highly proliferation cells (like cancer cells) which is encoded by the CD274 gene. The interaction between PD-1 and PD-L1 inhibits T cell growth and cytokine secretion. Therefore, PD-L1 negatively regulates immune responses and permits tumor cells to evade immune surveillance. Thus, PD-L1 seems to be a suitable target for designing the immune-therapeutics. Results The predicted structure of this protein indicated that the chains were linked by (Gly4Ser)3 linker. In that line, using different simulation software, the structure of Granzyme B (GrB), a serine protease exists in cytotoxic lymphocytes granules as an apoptosis mediator, was attached to its specific antibody structure (Atezolizumab) via an adaptor sequence. Evaluation of accuracy, energy minimization and characterization of biological properties of the final processed structure were done. Our computational outcomes showed that the method of employed structure prediction has been successfully managed to design the immunotoxin structure. Conclusion It is necessary to mention that the precise and accurate design of the immune-therapeutic agents against cancer cells, can be confirmed by employed in-silico approach. So, using this method, we have designed a capable immunotoxin targeting the PD-L1 in an accurate orientation and cause the cancer cell destruction by its toxin domain.

In this study, the factors that affect the selection of the types and characteristics of drilling fluids that were used while drilling nine wells in the Egyptian Western Desert were investigated. This study proves that the selection of drilling fluid type is not only based on the applications of drilling fluids, cost of drilling fluid or previous experience but also on other factors combined together such as geology of the area, potential problems for each section, make up base fluids availability, waste management techniques, environmental regulations, rig and drilling equipments and drilling data. In this study also, the evaluation of the designed characteristics of the selected types of drilling fluids was made to achieve the required functions such as good hole cleaning, well control, hole stability and to reduce lost circulation problem.