medRxiv - Hematology最新文献

{"title":"How many labels do I need? Self-supervised learning strategies for multiple blood parasites classification in microscopy images","authors":"Roberto Mancebo-Martin, Lin Lin, Elena Dacal, Miguel Luengo-Oroz, David Bermejo-Pelaez","doi":"10.1101/2024.02.29.24303535","DOIUrl":"https://doi.org/10.1101/2024.02.29.24303535","url":null,"abstract":"Bloodborne parasitic diseases such as malaria, filariasis or chagas pose significant challenges in clinical diagnosis, with microscopy as the primary tool for diagnosis. However, limitations such as time-consuming processes and the dependence on trained microscopists is critical, particularly in resource-constrained settings. Deep learning techniques have shown value to interpret microscopy images using large annotated databases for training. In this work, we propose a methodology leveraging self-supervised learning as a foundational model for blood parasite classification. Using a large unannotated database of blood microscopy images, the model is able to learn important image representations that are subsequently transferred to perform parasite classification of 11 different species of parasites requiring a smaller amount of labeled data. Our results show enhanced performance over fully supervised approaches, with ~100 labels per class sufficient to attain an F1 score of ~0.8. This approach is promising for advancing in-vitro diagnostic systems in primary healthcare settings.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140009017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53 mutation screening for patients at risk of myeloid malignancy","authors":"Devdeep Mukherjee, Rialnat A. Lawal, Courtney D. Fitzhugh, Christopher S. Hourigan, Laura W. Dillon","doi":"10.1101/2024.02.06.24302401","DOIUrl":"https://doi.org/10.1101/2024.02.06.24302401","url":null,"abstract":"There is increasing recognition of the risk of developing therapy-related myeloid malignancy, including after cellular therapy. While retrospective studies have implicated pre-existing <em>TP53</em> mutated hematopoietic clones as a common causative mechanism, no prospective screening to identify those patients at greatest risk is currently possible. We demonstrate that ultradeep DNA-sequencing prior to therapy may be used for discovery of <em>TP53</em> mutations that are subsequently associated with malignancy.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139759448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Stem Cell Infusion Timing in the Prevention of Acute Graft versus Host Disease","authors":"Yiwen Hou, Yue Wu, Zhonglin Zhang, Liang Wang, Zhiwei Liu, Baolin Tang, Kaidi Song, Guangyu Sun, Xiaoyu Zhu, Cheng Zhan","doi":"10.1101/2024.02.06.24302168","DOIUrl":"https://doi.org/10.1101/2024.02.06.24302168","url":null,"abstract":"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cornerstone treatment for a broad spectrum of malignant and nonmalignant hematological disorders. However, the success of allo-HSCT is often overshadowed by acute graft-versus-host disease (aGVHD), a life-threatening complication with limited preventive options. Here, we found that the incidence and severity of aGVHD after allo-HSCT are highly dependent on the circadian timing of stem cell infusion. The incidence rate of aGVHD in patients decreased by approximately 50% for early infusion (before 2:00 pm) compared to later infusion (after 2:00 pm). Early-infused patients also experienced significantly lower three-year transplant-related mortality and improved GVHD-free, relapse-free survival. Animal studies using an aGVHD mouse model show that this improvement is mainly due to the recipient’s rhythm rather than the donor’s. Mechanistically, compared with late infusions, early infusions significantly reduced the levels of the pro-inflammatory cytokine IL-1α following the conditioning regimen and subsequently suppressed T-cell activation and differentiation after transplantation. Our study suggests that scheduling stem cell infusions early in the day could be a simple yet transformative intervention for the prevention of aGVHD.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139759589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Frequency of Clonal Hematopoiesis of Indeterminate Potential in Bloom Syndrome Probands and Carriers","authors":"Isabella Lin, Angela Wei, Tsumugi A Gebo, PC Boutros, Maeve Flanagan, Nicole Kucine, C Cunniff, VA Arboleda, VY Chang","doi":"10.1101/2024.02.02.24302163","DOIUrl":"https://doi.org/10.1101/2024.02.02.24302163","url":null,"abstract":"<strong>Background</strong> Bloom Syndrome (BSyn) is an autosomal recessive disorder caused by biallelic germline variants in <em>BLM,</em> which functions to maintain genomic stability. BSyn patients have poor growth, immune defects, insulin resistance, and a significantly increased risk of malignancies, most commonly hematologic. The malignancy risk in carriers of pathogenic variants in <em>BLM</em> (<em>BLM</em> variant carriers) remains understudied. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by presence of somatic mutations in leukemia-related genes in blood of individuals without leukemia and is associated with increased risk of leukemia. We hypothesize that somatic mutations driving clonal expansion may be an underlying mechanism leading to increased cancer risk in BSyn patients and <em>BLM</em> variant carriers.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139761258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proliferative History Is a Novel Driver of Clinical Outcome in Splenic Marginal Zone Lymphoma","authors":"Helen Parker, Amatta Mirandari, Carolina Jaramillo Oquendo, Martí Duran-Ferrer, Benjamin Stevens, Lara Buermann, Harindra E. Amarasinghe, Jaya Thomas, Latha Kadalayil, Louise Carr, Shama Syeda, Methusha Sakthipakan, Marina Parry, Zadie Davis, Neil McIver-Brown, Aliki Xochelli, Sarah Ennis, Lydia Scarfo, Paolo Ghia, Christina Kalpadakis, Gerassimos Pangalis, Davide Rossi, Simon Wagner, Matthew Ahearne, Marc Seifert, Christoph Plass, Dieter Weichenhan, Eva Kimby, Lesley-Ann Sutton, Richard Rosenquist, Francesco Forconi, Kostas Stamatopoulos, Marta Salido, Ana Ferrer, Catherine Thieblemont, Viktor Ljungström, Rose-Marie Amini, David Oscier, Renata Walewska, Matthew J.J. Rose-Zerilli, Jane Gibson, José Ignacio Martín-Subero, Christopher Oakes, Dean Bryant, Jonathan C Strefford","doi":"10.1101/2024.01.16.24301320","DOIUrl":"https://doi.org/10.1101/2024.01.16.24301320","url":null,"abstract":"The epiCMIT (epigenetically-determined Cumulative MIToses) mitotic clock traces B-cell mitotic history via DNA methylation changes in heterochromatin and H3K27me3-containing chromatin. While high scores correlated with poor outcomes in CLL and MCL, its prognostic significance in SMZL remains unknown. Derived from 142 SMZL cases using DNA methylation microarrays, epiCMIT values were correlated with genomic, transcriptomic, and clinical data. EpiCMIT as a continuous variable was significantly higher in females (<em>p</em>=0.02), patients with IGHV1-2*04 allele usage (<em>p</em>&lt;0001), intermediate IGHV somatic hypermutation load (97-99.9% identity, <em>p</em>=0.04), elevated mutational burden (25 vs. 17 mut/Mb, <em>p</em>=0.001), driver gene mutations [<em>KLF2</em> (<em>p</em>&lt;0.001), <em>NOTCH2</em> (<em>p</em>&lt;0.01), <em>TP53</em> (<em>p</em>=0.01), <em>KMT2D</em> (<em>p</em>&lt;0.001)], and del(7q) (<em>p</em>=0.01). Negative correlation between epiCMIT and telomere length (r=-0.29 <em>p</em>&lt;0.001) supported the association between cumulated proliferation and telomere attrition. While univariate analysis highlighted epiCMIT as robust predictor of shorter treatment-free survival (TFS), multivariate analysis confirmed epiCMIT as an independent marker for shorter TFS. In summary, our matched multi-omic datasets facilitate the clinico-biological characterization of SMZL and introduces epiCMIT as a strong prognostic marker, identifying high-risk patients and predicting reduced treatment-free survival, hence providing a new tool for risk-adapted patient management.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139510463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing DOACs with warfarin in AF patients with chronic kidney disease or valvular disease: A systematic review and meta-analysis","authors":"Aileen Liang, Cathy Wang, Alla E Iansavichene, Alejandro Lazo-Langner","doi":"10.1101/2024.01.13.24301121","DOIUrl":"https://doi.org/10.1101/2024.01.13.24301121","url":null,"abstract":"<strong>Objective</strong> To analyze the safety and efficacy of different direct oral anticoagulant agents (DOACs) compared to warfarin in patients with concomitant atrial fibrillation (AF) and valvular disease or concomitant AF and chronic kidney disease (CKD).","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ensemble Model for Acute Myeloid Leukemia Risk Stratification Recommendations by Combining Machine Learning with Clinical Guidelines","authors":"Ming-Siang Chang, Cheng-Hong Tsai, Wen-Chien Chou, Hwei-Fang Tien, Hsin-An Hou, Chien-Yu Chen","doi":"10.1101/2024.01.08.24301018","DOIUrl":"https://doi.org/10.1101/2024.01.08.24301018","url":null,"abstract":"Acute Myeloid Leukemia (AML) is a complex disease requiring accurate risk stratification for effective treatment planning. This study introduces an innovative ensemble machine learning model integrated with the European LeukemiaNet (ELN) 2022 recommendations to enhance AML risk stratification. The model demonstrated superior performance by utilizing a comprehensive dataset of 1,213 patients from National Taiwan University Hospital (NTUH) and an external cohort of 2,113 patients from UK-NCRI trials. On the external cohort, it improved a concordance index (c-index) from 0.61 to 0.64 and effectively distinguished three different risk levels with median hazard ratios ranging from 18% to 50% improved. Key insights were gained from the discovered significant features influencing risk prediction, including age, genetic mutations, and hematological parameters. Notably, the model identified specific cytogenetic and molecular alterations like <em>TP53</em>, <em>IDH2</em>, <em>SRSF2</em>, <em>STAG2</em>, <em>KIT</em>, <em>TET2</em>, and karyotype (-5, -7, -15, inv(16)), alongside age and platelet counts. Additionally, the study explored variations in the effectiveness of hematopoietic stem cell transplantation (HSCT) across different risk levels, offering new perspectives on treatment effects. In summary, this study develops an ensemble model based on the NTUH cohort to deliver improved performance in AML risk stratification, showcasing the potential of integrating machine learning techniques with medical guidelines to enhance patient care and personalized medicine.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139412036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calling for diversity: improving transfusion safety through high-throughput blood group microarray genotyping","authors":"Michael Wittig, Tim Alexander Steiert, Hesham ElAbd, Frauke Degenhardt, Luca Valenti, Daniele Prati, Luisa Ronzoni, Luis Bujanda, Jesus M. Banales, Natalia Blay, Pietro Invernizzi, Maria Buti, Agustin Albillos, Javier Fernandez, Nicoletta Sacchi, Antonio Julia, Anna Latiano, Rafael de Cid, Mauro D'Amato, Rosanna Asselta, Matthias Laudes, Wolfgang Lieb, David Juhl, Christoph Gassner, Andre Franke","doi":"10.1101/2023.12.15.23299980","DOIUrl":"https://doi.org/10.1101/2023.12.15.23299980","url":null,"abstract":"Blood transfusions, conducted between donors compatible in their red blood cell (RBC) antigens, play a life-saving role in transfusion medicine. Genetic differences at blood group loci between ethnicities result in diversity and altered frequency of RBC antigens that need to be considered in blood transfusion. Consequently, comprehensive, and accurate blood group antigen typing is especially relevant for inter-ethnicity blood transfusions and for minorities underrepresented in the donor population. Blood group microarray genotyping is a cost-efficient and scalable method for comprehensive blood group typing. Previously, however, microarray typing has been challenging for the clinically important blood group systems Rh and MNS, as these feature highly paralogous genomic loci leading to mixed signals. We here present an approach for accurately typing blood group systems, including Rh and MNS variations, that we benchmarked in an ethnically diverse cohort. We tested its performance using gold-standard, diagnostic-grade MALDI-TOF data from 1,052-samples, including 334 HGDP-CEPH diversity panel samples and applied the approach to 4,999 samples of a COVID-19 genetics study. Overall, we obtained a 99.95% benchmarking concordance and 99.43% call rate. In summary, we provide a highly accurate and cost-efficient high-throughput genotyping method for comprehensive blood group analysis that is also suitable for ethnically diverse sample sets.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138744946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"von Willebrand factor-related values can predict bleeding events in patients with left ventricular assist devices","authors":"Ryuichi Taketomi, Ko Sakatsume, Shintaro Katahira, Kota Goto, Misako Suzuki, Zuo Yunan, Konosuke Sasaki, Midori Miyatake, Katsuhiro Hosoyama, Koki Ito, Yusuke Suzuki, Goro Takahashi, Kiichiro Kumagai, Hisanori Horiuchi, Yoshikatsu Saiki","doi":"10.1101/2023.12.15.23299936","DOIUrl":"https://doi.org/10.1101/2023.12.15.23299936","url":null,"abstract":"<strong>Background</strong> Recent advances in left ventricular assist device (LVAD) therapy have significantly contributed to the improved management of severe heart failure. The unignorable risk of bleeding events associated with the device therapy, however, remains to be addressed. Predictive factors for bleeding events are not fully defined.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138819994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of COVID-19 vaccines on patients with immune thrombocytopenic purpura: A protocol for a systematic review and meta-analysis","authors":"Yangyang Li, Demin Kong, Yicheng Ding, Jinhuan Wang","doi":"10.1101/2023.12.09.23298879","DOIUrl":"https://doi.org/10.1101/2023.12.09.23298879","url":null,"abstract":"<strong>Introduction</strong> Immune thrombocytopenic purpura (ITP) is characterized by a decrease in platelet counts and can be triggered by various factors, such as viral infections and vaccinations. Concerns have emerged regarding potential links between the vaccines for COVID-19 and the worsening of ITP. This systematic review aims to comprehensively assess the impact of COVID-19 vaccines on patients with ITP, including associated risks and outcomes.","PeriodicalId":501203,"journal":{"name":"medRxiv - Hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}