Hematology Research Research Articles

Kuruyemiş Alerjisi Olan Çocuklarda Klinik Bulgular ve Doğal Seyrin Değerlendirilmesi

Amac : Kuruyemis alerjileri (KA), anafilaksi gibi agir reaksiyonlara neden olabilmeleri ve yasla duzelme sikliklarinin az olmasi nedeni ile onemli bir saglik sorunudur. Calismamizda kuruyemis alerjilerinin klinik ozellikleri ve tolerans gelisiminin degerlendirilmesi amaclanmistir. Gerec ve Yontemler: Calismamizda T.C. Saglik Bilimleri Universitesi Ankara Cocuk Sagligi ve Hastaliklari Hematoloji Onkoloji Egitim ve Arastirma Hastanesi Cocuk Alerji Klinigi’nde 2010-2017 yillarinda kuruyemis alerjisi nedeni ile izlenen hastalarin klinik ozellikleri, laboratuvar bulgulari ve prognozu degerlendirildi. Bulgular: Calismaya ortanca yasi 2.5 yil (min-maks: 1-17) olan yuz yirmi sekiz (%73.4 erkek) hasta alindi. Hastalarin 109’unda (%85.2) findik, 60’inda (%46.8) ceviz 47’sinde (%36.7) antep fistigi, 37’sinde (28.9) badem, 22’sinde (%17.2) kaju fistigi alerjisi vardi. Kirk yedi (%36.7) hastada basvuru reaksiyonu anafilaksiydi. Takip suresi ortanca 56.3 (min-maks:16.3-134.2) aydi. Yuz yirmi sekiz hastanin 37’sinde (%29) tum KA’leri duzelmisken, 9’unda (%7) bazi KA’leri duzelmis 70 (%54.6) hastada ise KA devam etmistir. On iki hasta (%9.4) degerlendirilemedi. Tekli KA’li hastalarin %42’si, coklu KA’li hastalarin %31.5’i takip suresi icinde tolerans gelistirmistir. Sonuc: Kuruyemis alerjilerine tolerans gelisimi cesaret verici gorunuyor. Bu nedenle bu hastalarin duzenli takibi onemlidir.

Perspectives on Geriatric Hematology Research presented at the 2020 American Society of Hematology Annual Meeting: Young International Society of Geriatric Oncology report

The 2020 American Society of Hematology (ASH) Annual Meeting was held from December 5–8, 2020 virtually due to the COVID-19 pandemic. A scientific workshop on hematology and aging was held on Thursday, December 3, 2020. Topics discussed included biomarkers, clonal hematopoiesis of indeterminate potential (CHIP), chimeric antigen receptor T-cell (CAR-T) therapy, and thrombosis. A poster walk on “Hematology and Aging” was held December 10, 2020. We present a summary of selected oral and poster abstracts relevant to geriatric hematology, discussed by disease type.

Survival Factors ID'd for Patients with Blood Cancer + COVID-19.

Researchers launched the American Society of Hematology Research Collaborative COVID-19 Registry for Hematology in April to gather real-time data on patients with hematologic malignancies who develop COVID-19. Now, an analysis of the data reveals that 33% of patients with blood cancers who were hospitalized for COVID-19 died. Risk factors included older age, forgoing intensive treatment, and poor prognosis before infection.

Label-Free White Blood Cell Classification Using Refractive Index Tomography and Deep Learning.

Objective and Impact Statement. We propose a rapid and accurate blood cell identification method exploiting deep learning and label-free refractive index (RI) tomography. Our computational approach that fully utilizes tomographic information of bone marrow (BM) white blood cell (WBC) enables us to not only classify the blood cells with deep learning but also quantitatively study their morphological and biochemical properties for hematology research. Introduction. Conventional methods for examining blood cells, such as blood smear analysis by medical professionals and fluorescence-activated cell sorting, require significant time, costs, and domain knowledge that could affect test results. While label-free imaging techniques that use a specimen's intrinsic contrast (e.g., multiphoton and Raman microscopy) have been used to characterize blood cells, their imaging procedures and instrumentations are relatively time-consuming and complex. Methods. The RI tomograms of the BM WBCs are acquired via Mach-Zehnder interferometer-based tomographic microscope and classified by a 3D convolutional neural network. We test our deep learning classifier for the four types of bone marrow WBC collected from healthy donors (): monocyte, myelocyte, B lymphocyte, and T lymphocyte. The quantitative parameters of WBC are directly obtained from the tomograms. Results. Our results show >99% accuracy for the binary classification of myeloids and lymphoids and >96% accuracy for the four-type classification of B and T lymphocytes, monocyte, and myelocytes. The feature learning capability of our approach is visualized via an unsupervised dimension reduction technique. Conclusion. We envision that the proposed cell classification framework can be easily integrated into existing blood cell investigation workflows, providing cost-effective and rapid diagnosis for hematologic malignancy.

A toolkit for the collection of thrombosis-related data elements in COVID-19 clinical studies.

Thrombosis has emerged as an important complication of coronavirus disease 2019 (COVID-19), particularly among individuals with severe illness. However, the precise incidence of thrombotic events remains uncertain due to differences in study design, patient populations, outcome ascertainment, event definitions, and reporting. In an effort to overcome some of these challenges and promote standardized data collection and reporting in clinical studies, the American Society of Hematology Research Collaborative COVID-19 Non-Malignant Hematology Task Force, in collaboration with the International Society on Thrombosis and Haemostasis COVID-19 Task Force, developed sets of data elements in the following domains: venous thromboembolism, myocardial infarction, stroke/transient ischemic attack, peripheral arterial thrombosis, bleeding, laboratory investigations, and antithrombotic therapy. Data elements in each of these domains were developed with 3 levels of detail to facilitate their incorporation into studies evaluating a range of interventions and outcomes. Previously published data elements were included where possible. The use of standardized variables in a range of clinical studies can enhance the quality of data collection, create efficiency, enhance comparison of results across studies, and facilitate future pooling of data sets.

The hematology laboratory's response to the COVID-19 pandemic: A scoping review.

The ongoing COVID-19 pandemic has had a profound worldwide impact on the laboratory hematology community. Nevertheless, the pace of COVID-19 hematology-related research has continued to accelerate and has established the role of laboratory hematology data for many purposes including disease prognosis and outcome. The purpose of this scoping review was to assess the current state of COVID-19 laboratory hematology research. A comprehensive search of the literature published between December 1, 2019, and July 3, 2020, was performed, and we analyzed the sources, publication dates, study types, and topics of the retrieved studies. Overall, 402 studies were included in this scoping review. Approximately half of these studies (n=202, 50.37%) originated in China. Retrospective cohort studies comprised the largest study type (n=176, 43.89%). Prognosis/ risk factors, epidemiology, and coagulation were the most common topics. The number of studies published per day has increased through the end of May. The studies were heavily biased in favor of papers originating in China and on retrospective clinical studies with limited use of and reporting of laboratory data. Despite the major improvements in our understanding of the role of coagulation, automated hematology, and cell morphology in COVID-19, there are gaps in the literature, including biosafety and the laboratory role in screening and prevention of COVID-19. There is a gap in the publication of papers focused on guidelines for the laboratory. Our findings suggest that, despite the large number of publications related to laboratory data and their use in COVID-19 disease, many areas remain unexplored or under-reported.

Trial in Progress: Glad-AML - a Randomized, Phase 2 Trial of Glasdegib with Two Standard Decitabine Regimens for Older Patients with Newly-Diagnosed, Poor-Risk Acute Myeloid Leukemia

Trial in Progress: Glad-AML - a Randomized, Phase 2 Trial of Glasdegib with Two Standard Decitabine Regimens for Older Patients with Newly-Diagnosed, Poor-Risk Acute Myeloid Leukemia

Diffuse Large B Cell Lymphoma Genetic Classification By Targeted Sequencing and Associations with Immunochemotherapy-Treated Patients' Clinical Outcome

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease with variable prognosis associated with clinical features, cell-of-origin and genetic aberrations. The main problems for DLBCL patients are that a substantial percentage of them (30-40%) are refractory to treatment or relapse and the lack of accurate predictive markers that adequately determine which patients will benefit from immunochemotherapy. Several recent deep-sequencing studies have proposed new genetic subtypes based on the DLBCL genomic profile (Wright et al., 2020; Lacy et al. 2020) and associated with clinical outcome. However, a consensus and validated classification is still needed. The aim was to determine whether genetic alterations of individual genes or genes clustered in pathways are associated with clinical outcome in immunochemotherapy-treated patients. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicentric cohort of patients with DLBCL treated with rituximab-containing therapies with a median follow up of 6 years. A two-step genetic classifier was built with mutation information from 27 genes and BCL2/BCL6 translocations, based on recently proposed genetic subtypes (Wright et al., 2020; Lacy et al. 2020). Logistic regression and Kaplan-Meier analyses for survival and risk of relapse were performed to assess the potential clinical value of the classifier. Moreover, this two-step classifier was validated in an external cohort and its specificity and sensitivity were tested to determine its accuracy in classifying patients compared to the previous approaches. We found that the most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B, PRDM1, and NOTCH2 were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, PRDM1, and TNFAIP3 had significantly shorter survival. Analyzing the impact of gene mutations on predefined gene sets related to lymphomagenesis revealed that mutations in genes involved in B-cell development, and BCR-PI3K and MAPK-ERK pathways were significantly associated with a higher risk of relapse and/or shorter overall survival. These results confirmed the current landscape of genetic alterations in DLBCL. According to the two-step classifier, we categorized the samples into MCD, BN2, EZB, ST2, and N1 genetic subgroups (Figure). We tested the accuracy of our classification in an external series (UK population-based Haematological Malignancy Research Network cohort [HMRN]) to determine its specificity and sensitivity compared with their own classification (Lacy et al. 2020) and the LymphGen algorithm (Wright et al., 2020). The comparison demonstrated (Wright et al., 2020; Lacy et al. 2020), a specificity and sensitivity higher than 85% for each subtype, except for BN2. This controversy may be explained by the fact that BN2 is less strongly defined than the other subtypes. We then tested their clinical impact and found the EZB and ST2 subtypes to have a better clinical course and a lower risk of relapse. The BN2 group had the worst clinical outcome of our series, unlike other published studies (Figure). These results were validated in the HMRN cohort, in which N1 showed a higher risk of relapse and shorter overall survival, whereas ST2 is the group with the most favorable outcome. Although N1 was not included for clinical outcome analysis in our cohort due to the small number of cases, the validation of our classifier defined N1 as the most aggressive subtype. In summary, we propose and validate a feasible genetic DLBCL classifier based on an optimized panel of genes that unifies previous genetic classification algorithms in such a way as to facilitate its implementation as part of pathology laboratories for routine patient management. This genetic classifier, combined with clinical data and other molecular characteristics, should eventually help develop improved risk models for DLBCL patients, and guide precision therapy. Figure Disclosures Perez Callejo: F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company.

Characterization of the Immunoglobulin Heavy- and Light-Chain Repertoires in a Single Reaction

Background B cell repertoire analysis by next-generation sequencing (NGS) has shown particular utility in the field of hematological oncology research. Some advantages provided by NGS-based techniques include a lower limit-of-detection and simpler paths to standardization compared to flow-based methods, and the elimination of specifically designed primers often required for qPCR-based methods. Owing to primer-primer interactions and incompatibility of reaction conditions, current multiplex PCR assays require separate PCR reactions to survey each immunoglobulin chain (IGH, IGK, IGL), often leading to a longer time-to-answer for samples in which no marker is initially detected. We have developed an assay for receptor analysis based on Ion AmpliSeq technology to circumvent these issues, allowing the effective use of up to thousands of primers in a single reaction. The highly multiplexed, pan-clonality NGS assay provides for efficient detection of IGH, IGK, and IGL chain rearrangements in a single reaction. Methods We developed a single primer panel targeting the framework 3 (FR3) portion of the variable gene and the joining gene region of heavy- and light-chain loci (IGH, IGK, IGL) for all alleles found within the IMGT database, enabling readout of the complementary-determining region 3 (CDR3) sequence of each immunoglobulin chain. To maximize sensitivity, we included primers to amplify IGK loci rearrangements involving Kappa deletion and C intron elements. To evaluate performance, we conducted clonality assessment and limit-of-detection testing used gDNA from a total of 45 research samples representing common B cell malignancies. We included samples derived from peripheral blood, bone marrow, and FFPE-preserved tissues at input levels ranging from 100ng to 2µg. Finally, we further characterized the samples via a separate AmpliSeq-based multiplex PCR assay targeting rearranged TCRB and TCRG chains. Sequencing and clonality analysis was performed using the Ion GeneStudio S5 System and Ion Reporter 5.16. Results Clonality assessments carried out using gDNA collected from both cell line and clinical research samples (CLL, B-ALL, Multiple Myeloma, Burkitt's Lymphoma, NHL, and DLBCL) show a >90% overall positive detection rate. Assessment of linearity-of-response and limit-of-detection was carried out using cell lines diluted in PBL to between 10-3 and 10-6 by mass. The multi-receptor assay performs as expected, with linear response to the cell line frequency across the range tested, including the ability to detect clones of interest at 10-6. Conclusions These results demonstrate the robustness of our newly developed Ion AmpliSeq-assay for B cell receptor heavy and light chains. We expect this assay to simplify the workflow for clonality assessment and rare clone detection in B cell malignancy research. For research use only. Disclosures No relevant conflicts of interest to declare.

Increased Productivity and Efficiency Among Cancer Center Clinical Trials Workforce during the COVID-19 Pandemic

Increased Productivity and Efficiency Among Cancer Center Clinical Trials Workforce during the COVID-19 Pandemic

Somatic Mutations Associated with IgVH4-34 FR1 Region Unmutated QW and Avy Motifs in DLBCL Patients

There is increasing evidence for antigen-driven B-cell receptor (BCR) signalling in diffuse large B-cell lymphoma (DLBCL) and other lymphoid malignancies. This includes antigens from infections e.g.Helicobacter pyloriand Hepatitis C virus, but it is theorised that self-antigens may play a major role in some cases of lymphoid malignancy. IgVH4-34 demonstrates intrinsic autoreactivity to self-antigens on red cells, which appears to be largely mediated by two motifs within the first framework region (FR1); Q6W7 and A24V25Y26. These motifs work together to for a hydrophobic patch which determines red cell antigen binding and are frequently mutated away from self-reactivity in normal B cells. IgVH4-34 has been reported to be over-represented in DLBCL compared with expression in normal B cells. We therefore sought to identify IgVH4-34 DLBCL cases from a local cohort and to screen them for Q6W7 and A24V25Y26 motifs expecting them to be less frequently mutated in DLBCL compared with normal B cells.We also aimed to screen V4-34 cases for associated somatic mutations in other genes using high-throughput sequencing. DLBCL patient samples were obtained via the Haematology Research Tissue Bank (HRTB) in Canberra, Australia, and the Victoria Cancer BioBank. Forty-eight Formalin-Fixed, Paraffin-Embedded (FFPE) samples and 26 fresh frozen samples were screened. All samples were collected at the time of diagnosis. Patients were treated with standard chemoimmunotherapy approaches. IgVH 4-34 gene sequences were determined using an IgVH4 family-specific leader primer in combination with a JH consensus reverse primer. The IgVH region was then sequenced using Sanger sequencing. Sequences were analyzed using the IgBLAST database (National Centre for Biotechnology Information). DNA extracted from FFPE samples generally proved to have low concentration and fragmented DNA. Only 1 IgVH4-34 sequence was obtained from FFPE tissue. Five samples sequenced from fresh tissue were identified as using IgVH4-34. Using Hans criteria, it was possible to classify 3 of the 6 cases as germinal center (GC) and 1 as non-GC origin. Using fresh samples, we estimated the frequency of IgVH4-34 cases at 23%. Within FR1, Q6W7 was unmutated in all 6 samples. One sample had mutations in the A24V25Y26 motif resulting in a change to A24V25F26. The other 5 samples (83.3%) had unmutated AVY motifs. We extracted genomic DNA from and performed next generation sequencing on the 5 samples with unmutated Q6W7 and A24V25Y26 motifs using a customized capture library (SureSelectXT Target Enrichment System, Aqilent Technologies) covering genes involved in lymphomagenesis. The purified libraries were sequenced on the Illumina NextSeq500 platform at AGRF (Australian Genome Research Facility, Australia). Several genes (FCGR3A,NOTCH2andNOTCH2NLR) had mutations in all 5 samples.FCGR3Ais an IgG Fc receptor gene, and mutations inFCGR3Ahave previously been linked to systemic lupus erythematosus (SLE).NOTCH2pathway genes are frequently mutated in DLBCL.CREBBPwas mutated in four of the five samples. Mutations inCREBBPhave previously been linked with DLBCL development and regulation of immune responses. We identified high rates of IgVH4-34 (23%) in our cohort of fresh samples as previously reported. Further, we noted preservation of the Q6W7 and A24V25Y26 motifs in IgVH4-34-expressing DLBCL. This over-representation of unmutated FR1 motifs suggests that the ability to recognise self-antigens likely provides important ongoing BCR signalling that promotes survival in DLBCL. This study also highlights the difficulties in conducting DNA-based research on FFPE clinical samples which have not been collected for research purposes and the importance of tissue banking fresh samples. Studies are currently being conducted into the efficacy of BCR pathway inhibitors e.g. ibrutinib in the treatment of DLBCL and testing for unmutated IgVH4-34 FR1 motifs may present a method to predict patients who are more likely to respond. Mutations in genes such as FCGR3A,NOTCH2andCREBBPmay work in conjunction with the preserved QW and AVY motifs to promote lymphomagenesis in IgVH4-34-expressing B cells and may present targets for future research into treatment therapies. Figure Disclosures Talaulikar: Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Amgen:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda:Research Funding.

Outcomes of COVID-19 Infection in Patients with Hematologic Malignancies

The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic on March 11, 2020. This novel virus can cause a rapid progression from cough to acute respiratory distress syndrome and death. Cancer patients infected with COVID-19 were reported to have a 39% incidence of severe events, including admission to intensive care unit (ICU), mechanical ventilation, or death. Patients with hematologic malignancies, especially those undergoing treatment, are a particularly at-risk population due to disease-related impairment of the immune system and chemotherapy-induced neutropenia. The goal of this study is to analyze outcomes of COVID-19 infected patients with hematologic malignancies in order to better understand the impact of SARS-CoV-2 on this vulnerable population.MethodsWe performed a retrospective analysis on 26 COVID-19 positive patients with hematologic malignancies identified at our center. On July 22, 2020, there were 264 COVID-19 positive patients with hematologic malignancies (including our center's 26 patients) reported to the American Society of Hematology Research Collaborative COVID-19 Registry (ASH RC), a global public reference tool. We extracted our patient's data from each category reported to the ASH RC and compared hospitalization, ICU admissions, and mortality rates between our cohort and the remaining 238 cases. Chi-square test was used for analyses. We also performed a subgroup analysis comparing demographics; type and status of hematologic malignancy, as well as COVID-19 directed treatments between our center's patients and the patients reported to the ASH RC.ResultsBetween March and June 2020, a total of 1265 COVID-19 positive patients were hospitalized at our institution. A significantly higher percentage of COVID-19 patients with hematologic malignancies were hospitalized at our institution compared to the ASH RC (61.5% versus 35.3%, P=. 009). There was no difference in ICU admission rate at our center compared to the ASH RC (23.1% versus 30.2%, P=.45). Significantly less COVID-19 directed therapies were administered at our center compared to the ASH RC (46.2% versus 66.4%, P=.041). Our patients received: 7.7% Remdesivir, 11.5% Tocilizumab, 15.4% hydroxychloroquine, 11.5% azithromycin, 0% convalescent plasma, compared to the ASH RC: 1.7% Remdesivir, 5.5% Tocilizumab, 30.3% hydroxychloroquine, 25.6% azithromycin, 4.6% convalescent plasma. Lastly, our institution had a significantly decreased mortality rate compared to the ASH RC (11.5% versus 29.8%, P=.049). Demographics as well as type and status of hematologic malignancy comparing the two cohorts are shown in Table 1.ConclusionsIn our comparative analysis, we found that our center’s patients were hospitalized significantly more than the ASH RC cohort yet had lower mortality rates. These differences were seen despite similar distribution of malignancy types between the two groups. It should be noted that more patients in our cohort were in remission and none presented at initial cancer diagnosis at the time of infection, which may have contributed to better outcomes. The difference in mortality rates may also be attributed to variance in provider experience, higher percentage of patients >80 years of age reported to the ASH RC, and closer patient monitoring at our center due to a higher hospitalization rate. Differences in ICU admissions were not significant, suggesting a similar rate of severe COVID-19 infection between the two cohorts. Our demographics reflect the urban population we serve with more African Americans and Hispanics compared to the ASH RC. The greater number of COVID-19 directed therapies in the ASH RC cohort compared to ours is likely attributed to the use of convalescent plasma, which was not commonly used as COVID-19 directed treatment at our institution. Limitations of our study include a restricted time frame, small sample size, and the possibility of incomplete datasets within the ASH RC, as stated on the registry’s website. In conclusion, we recommend close monitoring and a lower threshold for hospitalizing patients with hematologic malignancies in the setting of COVID-19 infection; however, additional prospective studies are needed to confirm our findings, and further investigate the complications and outcomes of SARS-CoV-2 on this at-risk population.DisclosuresUstun:Kadmon: Honoraria. Shammo:Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Onconova: Research Funding; Incyte: Consultancy, Research Funding, Speakers Bureau; Apellis: Consultancy; Regeneron: Consultancy; Novartis: Consultancy; Agios: Consultancy; Sanofi: Speakers Bureau; Abbive: Current equity holder in publicly-traded company; Baxter: Current equity holder in publicly-traded company; Takeda: Current equity holder in publicly-traded company; Alexion: Consultancy, Research Funding, Speakers Bureau.

Peer review declaration

All papers published in this volume of IOP Conference Series: Earth and Environmental Science have been peer reviewed through processes administered by the Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing. • Type of peer review: Single-blind • Conference submission management system: The submission process had no a software system. Call-for-paper was placed on the Conference web page (https://pasd-conf.ru/), the papers were submitted via e-mail (zykovaap@mail.ru). The reviews were asked and received via e-mails of Editors. • Number of submissions received: 89 • Number of submissions sent for review: 60 • Number of submissions accepted: 44 • Acceptance Rate (Number of Submissions Accepted / Number of Submissions Received X 100): 49% • Average number of reviews per paper: 1.9 • Total number of reviewers involved: 118 • Any additional info on review process: The consideration of the submitted manuscript included independent peer review process. At least two reviewers gave their view and remarks for each paper. All Reviewers were asked to provide a detailed review with comments for authors and editors and evaluate paper taking into account the questions list (Is this work novel? Is this work scientifically correct (the experimental procedure and sequence)? Does the subject significantly advance research in the fields of research? Does it have high scientific quality? Does this work have significant proof to verify the primary hypothesis? Is this work incremental? Is the paper clearly written, concise and understandable? Should the English be improved? Is the paper scientifically sound and not misleading?). All Reviewers also were asked to provide their recommendations about paper acceptance (to publish the paper “as is”; to publish the paper after minor revision; to publish the paper after major revision; to reject the paper). • Contact person for queries: Dr. Anton Stepanov, Laboratory of Hematological Research, Chuvash State Agricultural Academy, Cheboksary, Russian Federation, For.Anton step@edu.academy21.ru

Preface

International AgroScience Conference (AgroScience-2020) 10 April 2020 Cheboksary, Russian Federation The Conference AgroScience-2020 was jointly organized by Chuvash State Agricultural Academy (Russia), Life Science University of Bradford (United Kingdom), Grodno State Agrarian University (Republic of Belarus), and Research Institute of Livestock and Feed Production (Republic of Kazakhstan).The purpose of AgroScience-2020 was to bring together scientists, academicians, practitioners, and professionals from manufacturing sector in the fields of agro-science, agro-engineering, and agro-technology. The conference program was structured to encourage mutual inspiration and fruitful debate among researcher. Participants were offered the chance to contribute to the conference in various roles, to demonstrate novel results, and to exchange new ideas and application experiences with each other.AgroScience-2020 was mainly emphasized on (1) Actual issues of production and processing of agricultural products; (2) Actual problems of livestock and veterinary medicine; (3) Agroengineering: state and prospects; and (4) Economics and management: challenges and directions of development.We are especially grateful to our Participants and Institutions for their contribution in the event. All the manuscripts included to the Proceedings went through intensive reviews by experts in in the fields of agro-science, agro-engineering, and agro-technology from Philippines, Brazil, Egypt, Ukraine, Canada, Russia, Italy, China, Poland, Pakistan, Mexico, India, Indonesia, Spain, Latvia, Syria, Saudi Arabia, Yemen, USA, Argentina, United Arab Emirates, France, Sudan, Brunei, Malaysia, and Columbia. The Editors appreciate the enthusiasm of all Reviewers and authors to improve the quality of the papers.Web page of the AgroScience-2020: https://pasd-conf.ru/ Organizing Committee:Dr. Anton Stepanov, Laboratory of Hematological Research, Chuvash State Agricultural Academy, Cheboksary, Russian Federation Editors of the Special Issue AgroScience-2020:Prof. Andrei Mardaryev, School of Chemistry and Biosciences, Faculty of Life Science University of Bradford, United KingdomDr. Anna Godymchuk, Chemistry Environmental Laboratory, Tobolsk Complex Scientific Station, Ural Branch of the Russian Academy of Science, Russian FederationDr. Natalia Karakchieva, Laboratory of Chemical Technologies, National Research Tomsk State University, Russian Federation

Professor Shigetaka Asano: extraordinary Japanese haematologist and bon vivant February 7, 1943 to August 12, 2020.

Profs. Satoshi Takahashi and Arinobu Tojo (IMSUT) kindly reviewed the typescript. RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Jichi Medical University, Tochigi-Ken, Japan Keiya Ozawa Tokyo Cord Blood Bank, Tokyo, Japan Hideki Kodo Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK Robert Peter Gale You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Robert Peter Gale. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Ozawa, K., Kodo, H. & Gale, R.P. Professor Shigetaka Asano: extraordinary Japanese Haematologist and Bon Vivant February 7, 1943 to August 12, 2020. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01061-4 Download citation Received: 24 August 2020 Revised: 02 September 2020 Accepted: 09 September 2020 Published: 18 September 2020 DOI: https://doi.org/10.1038/s41409-020-01061-4

Professor Shigetaka Asano: extraordinary Japanese Haematologist and Bon Vivant February 7, 1943 to August 12, 2020

Profs. Satoshi Takahashi and Arinobu Tojo (IMSUT) kindly reviewed the typescript. RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Jichi Medical University, Tochigi-Ken, Japan Keiya Ozawa Tokyo Cord Blood Bank, Tokyo, Japan Hideki Kodo Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK Robert Peter Gale You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Robert Peter Gale. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Ozawa, K., Kodo, H. & Gale, R.P. Professor Shigetaka Asano: extraordinary Japanese Haematologist and Bon Vivant February 7, 1943 to August 12, 2020. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01061-4 Download citation Received: 24 August 2020 Revised: 02 September 2020 Accepted: 09 September 2020 Published: 18 September 2020 DOI: https://doi.org/10.1038/s41409-020-01061-4

Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020

Khot S, Park BS, Longstreth WT Jr. The Vietnam War and medical research: untold legacy of the U.S. Doctor Draft and the NIH “Yellow Berets”. Acad Med. 2011;86:502–8. PubMed Article Google Scholar Download references RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK Robert Peter Gale Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA Hillard M. Lazarus Wake Forest Comprehensive Cancer Center, Winston-Salem, NC, USA Gordon L. Phillips II You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Robert Peter Gale. The authors declare they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Gale, R.P., Lazarus, H.M. & Phillips, G.L. Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01055-2 Download citation Received: 30 July 2020 Revised: 14 August 2020 Accepted: 02 September 2020 Published: 09 September 2020 DOI: https://doi.org/10.1038/s41409-020-01055-2

Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020.

Khot S, Park BS, Longstreth WT Jr. The Vietnam War and medical research: untold legacy of the U.S. Doctor Draft and the NIH “Yellow Berets”. Acad Med. 2011;86:502–8. Article Google Scholar Download references RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK Robert Peter Gale Department of Medicine, Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH, USA Hillard M. Lazarus Wake Forest University Comprehensive Cancer Center, Winston Salem, NC, USA Gordon L. Phillips II You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Robert Peter Gale. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Gale, R.P., Lazarus, H.M. & Phillips, G.L. Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020. Leukemia (2020). https://doi.org/10.1038/s41375-020-01027-x Download citation Received: 30 July 2020 Revised: 05 August 2020 Accepted: 11 August 2020 Published: 09 September 2020 DOI: https://doi.org/10.1038/s41375-020-01027-x

Matteo Adinolfi: immunologist focusing on prenatal diagnosis of gene disorders

Matteo Adinolfi was born in 1928 in Asmara, Eritrea, to Attilio, a bank manager, and his wife, Maria (nee Sellitti), who had fled there from Italy to escape fascism. His...

Over 60 Years of Experimental Hematology (without a License)

I am deeply honored to receive the International Society for Experimental Hematology (ISEH) 2020 Donald Metcalf Lecture Award. Although I am not a physician and have had no formal training in hematology, I have had the privilege of working with some of the top hematologists in the world, beginning in 1970 when Dr. David Nathan was a sabbatical visitor in my laboratory and introduced me to hematological diseases. And I take this award to be given not just to me but to an exceptional group of MD and PhD trainees and visitors in my laboratory who have cloned and characterized many proteins and RNAs important for red cell development and function. Many of these projects involved taking exceptionally large risks in developing and employing novel experimental technologies. Unsurprisingly, all of these trainees have gone on to become leaders in hematology and, more broadly, in molecular cell biology and molecular medicine. To illustrate some of the challenges we have faced and the technologies we had to develop, I have chosen several of our multiyear projects to describe in some detail: elucidating the regulation of translation of α- and β-globin mRNAs and the defect in beta thalassemia in the 1970s; cloning the Epo receptor and several red cell membrane proteins in the 1980s and 1990s; and more recently, determining the function of many microRNAs and long noncoding RNAs in red cell development. I summarize how we are currently utilizing single-cell transcriptomics (scRNAseq) to understand how dividing transit-amplifying burst-forming unit erythroid progenitors balance the need for more progenitor cells with the need for terminally differentiated erythroid cells, and to identify drugs potentially useful in treating Epo-resistant anemias such as Diamond Blackfan anemia. I hope that the lessons I learned in managing these diverse fellows and projects, initially without having grants to support them, will be helpful to others who would like to undertake ambitious and important lines of research in hematology.