bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Interaction of Sickle Cell Trait and Anticardiolipin Antibodies in Venousthromboembolism
Authors: Ezekekwu Chinedu A , Kotila Taiwo R , Anyanwu-Yeiya Chinonso Chiemeka , Akingbola Titilola S. , Tayo Bamidele 
Published: November 2021

Abstract
Introduction
Among the risk factors for venous thromboembolism (VTE) are inheritance of the sickle cell gene and antiphospholipid syndrome. Antiphospholipid antibodies are elevated in sickle cell disease but there is little information on its levels in sickle cell trait. The prevalence of anticardiolipin antibodies and association with VTE is equally not known in the Nigerian population.
Methods
A case control study involving 50 consecutive patients with Doppler confirmed venous thromboembolism at the University College Hospital Ibadan and 50 apparently healthy individuals. Haemoglobin electrophoresis was carried out using cellulose acetate membrane. IgG and IgM anticardiolipin antibodies were assayed by ELISA.
Results
The mean age of the patients was 58.7±18.5years, range of 21-89 years, there were 21 males (42%). Majority of the patients (42 (84%)) had deep venous thrombosis while five (10%) patients presented with pulmonary embolism, one had both deep venous thrombosis and pulmonary embolism. A patient had portal vein thrombosis and another, an intracardiac clot. Sedentary lifestyles, hypertension and concomitant malignancy were the most prevalent risk factors (34% each) (figure I). Both sedentary lifestyle and cancer were significantly associated with VTE (p&lt;0.001). Sickle cell trait (Hb AS) occurred in the same number of patients and controls (eleven each). Higher levels of both IgG and IgM anticardiolipin antibodies were found among the VTE patients with sickle cell trait than controls. (Table 1) The mean levels of IgG antibody in Hb AS patients was 31.7 ± 12.8 GPL compared to 25 ± 13.8 GPL in the controls (p= 0.254) and mean IgM anticardiolipin antibodies in Hb AS patients was 18.7 ± 6.2 GPL while that of the controls was 16.8 ± 11.6 GPL (p= 0.633). The global mean levels of IgG and IgM anticardiolipin antibodies in the patients with VTE were 29.7 ± 9.1 GPL and 24.8 ±16.7 GPL respectively versus 28.5 ±13.7 GPL and 25.2 ±16.2 GPL in the controls. A multivariable logistic regression showed age, sedentary lifestyle and anemia as independent risk factors while a positive IgM anticardiolipin antibody appeared protective for VTE. (Table 2)
Conclusion
The prevalence of sickle cell trait and anticardiolipin levels did not differ between VTE patients and healthy controls. Age, hypertension, sedentary lifestyle and malignancies were identified risk factors in our cohort of patients. Larger prospective studies may be helpful in determining the influence of sickle cell trait and antiphospholipid antibodies in venous thromboembolism.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Thrombosis in Patients with Post-Polycythemia Vera Myelofibrosis: Incidence and Risk Factors
Authors: Teng Guangshuai , Zhang Yuhui , Gao Chao , Hu Naibo , Du Chenxiao , Bai Jie 
Published: November 2021

Abstract

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV). Post PV myelofibrosis (MF) is the advanced phase in the natural progression of PV. To explore the risk factors for thrombosis in post-PV MF, clinical characteristics, laboratory characteristics, the incidence of thrombosis and survival were retrospectively analyzed in a cohort of 163 Chinese patients with post-PV MF. The Kaplan-Meier method and multivariate Cox analysis were used to identify the risk factors and a risk model for thrombosis was established. Among the 163 patients, the median follow-up duration was 6 (1-18) years. During follow-up, 84 (51.5%) patients developed thrombosis, 11 (6.7%) patients progressed to acute leukemia, and 35 (21.5%) patients died (20% of whom died due to thrombosis). The 5-year, 10-year, and 15-year thrombosis-free survival (TFS) rates were 59.8%, 28.2%, and 9%, respectively. The TFS time of the post-PV MF patients was significantly lower than that of the age- and sex-matched PV patients (P&lt;0.001). The incidence of venous thrombosis was significantly higher after the diagnosis of post-PV MF than before or at the time of the diagnosis, and the proportions of patients with JAK 2 V617F allele burden ≥75% or absolute monocyte count ≥1.5×10 9/L was significantly higher in the venous thrombosis group than in the group without venous thrombosis (P&lt;0.05). Multivariate analysis showed that palpable splenomegaly (P=0.008, HR=3.284, 95% CI [1.373,7.855]), age ≥60 years (P=0.048, HR=1.604, 95% CI [1.004,2.56]), and a history of thrombosis (P&lt;0.001, HR=2.767, 95% CI [1.735, 4.412]) were risk factors for thrombosis in post-PV MF patients, then a risk model for thrombosis was established according to these data. The median TFS durations in patients in the extremely high-risk group, high-risk group, intermediate-risk group, and low-risk group were 2 years, 4 years, 9 years, and 13 years, respectively. In summary, post-PV MF patients have a higher incidence of thrombosis. Reducing the volume of the spleen and the allele burden of JAK2 V617F is critical to prevent thrombosis in post-PV MF patients.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Mesenchymal Stromal Cell-Derived S100A8 Promotes Acute Myeloid Leukemia Progression Via ROS Signaling
Authors: Wu Jinxian , Liu Xiaoyan , Zhou Fuling 
Published: November 2021

Abstract
Introduction: Mesenchymal stromal cell (MSC) is an important cell component in the bone marrow microenvironment. MSC-derived inflammatory factors regulate the progression of acute myeloid leukemia (AML) by regulating the signaling pathways in hematopoietic cells. S100A8 is an inflammatory factor which belong to the calcium-binding protein S100 family. In vivo animals experiments showed that increased expression of S100A8 in MSC was accompanied by increased proliferative MSCs, and decreased mature osteoblasts. MSC-derived S100A8 can also cause mitochondrial dysfunction in hematopoietic stem progenitor cells, induce oxidative stress response and DNA damage repair, that promotes the progression of myeloid dysplastic syndromes (MDS). However, whether MSC-derived S100A8 involved in AML development have not been reported. In this study, we attempted to elucidate the regulation of MSC-derived S100A8 on MSC itself as well as leukemia cells.
Methods: Human MSCs were isolated from AML patients samples by whole bone marrow adherent culture, and the third to fifth passage cells were collected for analysis. The lentivirus vector carrying cDNA of S100A8 gene and the empty lentivirus vector were constructed and infected into MSCs,respectively. Cell cycle and apoptosis of MSCs were analysed by flow cytometry. Acute myeloid leukemia cell line Kasumi-1 was co-cultured with the two groups of mesenchymal stem cells in vitro for 3 days, respectively.cell cycle and apoptosis were analysed, and the cell proliferation was detected by Edu. The ROS levels of co-cultured Kasumi-1 cells were detected by flow cytometry. The apoptosis of kasumi-1 co-cultured cells treated with VP-16 for 48 hour was detected by flow cytometry.
Results: The rate of G0 phase cell in S100A8-overexpressed MSCs was higher than in control group.The proliferation rate of Kasumi-1 cells was significantly increased S100A8 overexpressed group than in control after 72-h co-culture, while the apoptosis rate of Kasumi-1 cells was significantly decreased in S100A8 overexpressed group. Futhermore, the apoptosis rate of Kasumi-1 cells co-cultured with S100A8-overexpressed MSCs was markedly lower than in control group after exposed in vp-16 for 48 hour.The ROS level of Kasumi-1 cells co-cultured with S100A8-overexpressed MSCs were significantly increased than those of the control group.
Conclusion: S100A8 derived from MSCs plays a critical role in progression and drug resistance of acute myeloid leukemia, by increasing the ROS levels of AML cells, that indicates S100A8 may serve as a potential novel therapeutic target in AML.

Disclosures
No relevant conflicts of interest to declare.
Sex Differences in EBV Viremia after Haplo-HSCT Imply Sex Bias during Immune Reconstitution
Authors: Wei Rong , Xu Lanping , Huang Xiaojun 
Published: November 2021

Abstract
Objective: Posttransplant infection is common and tough to deal, patients after HSCT rely on immune reconstitution for protection. We desperately need a deeper understanding of how the system works to help the patients overcome the infection.
Method: This study analyzed the disease course of EBV viremia after haplo-HSCT, as well as the laboratory testing data. The sex bias during immune reconstitution was manifested by comparing the outcomes between male and female patients,
Results: 236 patients received haplo-HSCT in 2013 in our center, at a median follow up of 5 years, among whom 78 patients underwent EBV infection. The incidence of EBV viremia after transplantation is 33.1% in total, with a significant difference between men and women (40.0% and 26.7% respectively, p=0.034). Men tended to have earlier onset time (14-434d after HSCT) and longer duration (7-70d) than women (17-592d after HSCT, 7-30d). Both the initial and peak viral load were higher in men than in women (initial viral load＞10 4/ml: men 6.52% vs. women 3.13%, peak viral load＞10 5/ml: men 8.70% vs. women 3.13%). To explain this phenomenon, we analyzed the laboratory testing data on 30d and 60d after HSCT. And we found that male patients had higher plasma levels of immunoglobulin M on 60d after HSCT if infected by EBV, referring to more robust induction of innate immune (p=0.033). By contrast, female patients had significantly increased CD4+ T cell during EBV infection, representing more robust activation of adaptive immune (p=0.019).
Conclusion: These findings provide a possible explanation for the observed sex biases in EBV viremia after haplo-HSCT, and provide an important basis for the recognition of immune reconstitution, furthermore, raise concern of the development of a sex-based approach to the treatment and care of male and female patients with infection after HSCT.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
FISH-Guided Evaluation of Hyperdiploidy and Other Cytogenetic Abnormalities in Childhood Burkitt Lymphoma
Authors: Avgerinou Georgia , Filippidou Maria , Kostopoulos Ioannis V , Exarchos Athanasios , Stefanaki Kalliopi , Binenbaum Ilona , Liapis Konstantinos , Kossiva Lydia , Katsibardi Katerina , Polychronopoulou Sophia , Mantzourani Marina , Kattamis Antonis , Papadhimitriou Stefanos 
Published: November 2021

Abstract
Background: Burkitt lymphoma (BL) is the most common lymphoma in childhood. Apart from MYC rearrangement, considered the hallmark of the disease, BL often presents with additional chromosome aberrations, the biological and clinical significance of which is not fully understood. Materials and methods: The study included 72 children (55 boys, 17 girls), aged 2-16 years (median 9), with BL diagnosed on the basis of histopathology and a demonstrable MYC rearrangement. Touch imprints from the diagnostic biopsy samples were investigated with i-FISH for MYC, BCL2, BCL6, IGH, IGK and IGL rearrangements genes and copy number aberrations involving 1q21/1p32, 7cen/7q31, 9cen/9p21, 13q14/13q34 and 17cen/17p13. Deviations from the diploid status were further investigated for aneusomies of the carrier chromosome with the use of appropriate chromosome enumeration probes. Results: MYC gene was demonstrated in all cases with MYC/IGH fusion in 83.3% (60/72). 47 cases (65.3%) were found with least one additional aberration, most commonly with 1q gain (29.2%), 7q gain (19.4%), 13q deletion (19.4%), hemizygous 9p loss (8.3%) and hyperdiploidy (8.3%). Advanced clinical stage (IV), 7q gain (but not trisomy 7) and -9/9p- were significantly associated with shorter overall survival. There was no instance of relapse or death among the hyperdiploid cases. Conclusions: This extensive FISH investigation on imprints of affected tissue provides clinically meaningful information on the genetic profile of BL and may prove valuable in the management of patients with no karyotype available. In particular, the demonstration of hyperdiploidy through the use of chromosome enumeration probes could offer the means for the delineation of clonal evolution pathways and the recognition of a subgroup of children with excellent prognosis who could be cured with low-intensity chemotherapy regimens.

Disclosures
Kattamis: VIFOR: Consultancy; CRISPR/Vertex: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; BMS/Celgene: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy.
IKZF1deletions Coupled with CD20 Expression Represents a Novel High-Risk Subtype in Adult B-Cell Progenitor Acute Lymphoblastic Leukemia
Authors: Tang Bingqing , Wang Zhixiang , Lin Dainan , He Xianjun , Cai Zihong , Huang Kangyu , Zhou Xuan , Lin Ren , Xiaoli Liu , Xu Na , Huang Fen , Sun Jing , Liu Qifa , Zhou Hongsheng 
Published: November 2021

Abstract
Genetic deletions of IKZF1 are associated with poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Here we investigated the effect of IKZF1 deletions (IKZF1 del) plus with immunotype in adult B-ALL in PDT-ALL-2016 cohort. This cohort study involved 161 patients with B-ALL from 2016 to 2019, with detailed information about IKZF1 del and CD20 expression. Validation cohort consists N= patients from TARGET cohort. IKZF1 del was detected in 36.0% of patients with 3-year event-free survival (EFS) of 37.2±6.7% and overall survival (OS) of 51.1±7.3%, compared to IKZF1 wild-type (IKZF1 wt) with EFS 55.4±5.1% (P&lt;0.01) and OS 74.6±4.5% (P&lt;0.05), respectively. CD20 expression was also associated with inferior EFS than CD20-negative group (P&lt;0.05). Furthermore, IKZF1 del coupled with CD20 expression, termed as IKZF1 del/CD20+, comprised 12.4% of patients with 3-year EFS of 25.0±9.7% compared with IKZF1 wt (P&lt;0.05 ) and IKZF1 del/CD20- (P&lt;0.05 ) groups, respectively. Multivariable analyses demonstrated independence of IKZF1 del/CD20+ with highest hazard ratio for EFS and OS. Furthermore, the prognostic strength of IKZF1 del/CD20+ was confirmed in TARGET validation cohort. Eighty-one patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Notably, neither IKZF1 del(P=0.6288), CD20 (P=0.0705) or IKZF1 del/CD20 (P=0.3410) groups were identified as poor outcome in allo-HSCT cohort. Collectively, our data demonstrate that IKZF1 del/CD20+ represents a very high-risk subtype in adult B-ALL; and particularly, allo-HSCT could overcome the poor outcome of IKZF1 del and IKZF1 del/CD20+.

Disclosures
No relevant conflicts of interest to declare.
Second Malignant Neoplasms (SMN) in Myeloma Patients Post Stem Cell Transplant (SCT)
Authors: Kulkarni Samar , Murray John , Cavet Jim , Dennis Mike , Bloor Adrian , Patel Amit , Castleton Anna , Tomlins Joanna 
Published: November 2021

Abstract

Introduction: Recent developments in management of patients with myeloma have resulted in longer survival. Availability of newer class of agents for treatment has prolonged survival, improved quality of life and achieved better disease control. Use of SCT, either autologous (AutoSCT) and to a lesser extent allogeneic (AlloSCT) still forms an important aspect of myeloma treatment pathway. Improved survivorship mandates evaluation of long term consequences and risk of SMN is one of the most important long-term consequences affecting overall outcome.
Aim: Estimate the risk of SMN post SCT in patients with Myeloma.
Methods and Materials: Analysis includes 779 patients who received SCT for myeloma from January 2002 to December 2019. Data was collected using case records, electronic patient records, transplant database and information from referring hospitals. Follow-up was updated to June 2020.
Results: Analysis includes 779 patients with myeloma (M: 488, F:291; median age:59yr, range: 26-75) receiving AutoSCT (n=716) or AlloSCT (n=63). Conditioning for AutoSCT was high dose melphalan in majority (n=714, 99.7%). AlloSCT conditioning was RIC (n=40/63, 63.5%) or MAC (n=23/63, 36.5%). TBI was part of conditioning in 51/779 (6.5%). There was no difference in demographics between two groups.
Results: Median follow-up was 46 mo (range: 0.2-220). Second malignancy was identified in 48 of 779 cases (6.0%). SMN developed in 6/63 (10%) AlloSCT and 42/716 (6%) AutoSCT patents (p=0.25). SMN types were haematological (n=21), lymphoma (n=6) and solid tumours (n=21). MDS was the only haematological SMN in this series. Secondary MDS developed in 20/21 of AutoSCT as compared to 1/63 in AlloSCT (p=0.01). Non-haematological SMN were breast (n=3), upper GI (n=3), lower GI (n=2), hepato-billiary (n=2), prostate (n=3), skin (n=5), and unknown primary (n=1). SMN incidence was higher with increasing follow-up (2002-2014, 8%; 2015-2017, 2.8%, 2018-2019, 0%, p=0.002). There was no association with development of SMN and gender, age at transplant, type of stem cell source or transplant conditioning. Incidence of SMN was significantly higher for all sites as compared to general population. Cumulative incidence of SMN was 5% at 5 yr, and 15% at 10 yr for AutoSCT patients.
Conclusion: Myeloma patients are at increased risk of SMN and need monitoring for long term side effects. Development of MDS post AutoSCT is the commonest SMN post AutoSCT but there is increased incidence of solid tumours as well. Impact of new modalities of treatment needs long term monitoring.

Disclosures
Bloor: Novartis: Honoraria; Kite, a Gilead Company: Honoraria.
The diversity among the species Tetragenococcus halophilus including new isolates from a lupine seed fermentation
Authors: Link Tobias , Vogel Rudi F. , Ehrmann Matthias A. 
Published: November 2021

Abstract
Background
Tetragenococcus (T.) halophilus can be isolated from a variety of fermented foods, such as soy sauce, different soy pastes, salted fish sauce and from cheese brine or degraded sugar beet thick juice. This species contributes by the formation of short chain acids to the flavor of the product. Recently, T. halophilus has been identified as a dominant species in a seasoning sauce fermentation based on koji made with lupine seeds.

Results
In this study we characterized six strains of T. halophilus isolated from lupine moromi fermentations in terms of their adaptation towards this fermentation environment, salt tolerance and production of biogenic amines. Phylogenic and genomic analysis revealed three distinctive lineages within the species T. halophilus with no relation to their isolation source, besides the lineage of T. halophilus subsp. flandriensis. All isolated strains from lupine moromi belong to one lineage in that any of the type strains are absent. The strains form lupine moromi could not convincingly be assigned to one of the current subspecies. Taken together with strain specific differences in the carbohydrate metabolism (arabinose, mannitol, melibiose, gluconate, galactonate) and amino acid degradation pathways such as arginine deiminase pathway (ADI) and the agmatine deiminase pathway (AgDI) the biodiversity in the species of T. halophilus is greater than expected. Among the new strains, some strains have a favorable combination of traits wanted in a starter culture.

Conclusions
Our study characterized T. halophilus strains that were isolated from lupine fermentation. The lupine moromi environment appears to select strains with specific traits as all of the strains are phylogenetically closely related, which potentially can be used as a starter culture for lupine moromi. We also found that the strains can be clearly distinguished phylogenetically and phenotypically from the type strains of both subspecies T. halophilus subsp. halophilus and T. halophilus subsp. flandriensis.
A NAC transcription factor OsNAC3 positively regulates ABA response and salt tolerance in rice
Authors: Zhang Xiang , Long Yan , Chen Xingxiang , Zhang Baolei , Xin Yafeng , Li Longying , Cao Shuling , Liu Fuhang , Wang Zhigang , Huang Hao , Zhou Degui , Xia Jixing 
Published: November 2021

Abstract
Background
NAC (NAM, ATAF and CUC) transcription factors (TFs) play vital roles in plant development and abiotic stress tolerance. Salt stress is one of the most limiting factors for rice growth and production. However, the mechanism underlying salt tolerance in rice is still poorly understood.

Results
In this study, we functionally characterized a rice NAC TF OsNAC3 for its involvement in ABA response and salt tolerance. ABA and NaCl treatment induced OsNAC3 expression in roots. Immunostaining showed that OsNAC3 was localized in all root cells. OsNAC3 knockout decreased rice plants’ sensitivity to ABA but increased salt stress sensitivity, while OsNAC3 overexpression showed an opposite effect. Loss of OsNAC3 also induced Na+ accumulation in the shoots. Furthermore, qRT-PCR and transcriptomic analysis were performed to identify the key OsNAC3 regulated genes related to ABA response and salt tolerance, such as OsHKT1;4, OsHKT1;5, OsLEA3–1, OsPM-1, OsPP2C68, and OsRAB-21.

Conclusions
This study shows that rice OsNAC3 is an important regulatory factor in ABA signal response and salt tolerance.
Diagnostic performance of a wearing dynamic ECG recorder for atrial fibrillation screening: the HUAMI heart study
Authors: Fu Wenxia , Li Ruogu 
Published: November 2021

Abstract
Background
Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia with high morbidity and mortality rate. Evidence shows that in every three patients with AF, one is asymptomatic. The asymptomatic and paroxysmal nature of AF is the reason for unsatisfactory and delayed detection using traditional instruments. Research indicates that wearing a dynamic electrocardiogram (ECG) recorder can guide accurate and safe analysis, interpretation, and distinction of AF from normal sinus rhythm. This is also achievable in an upright position and after exercises, assisted by an artificial intelligence (AI) algorithm.

Methods
This study enrolled 114 participants from the outpatient registry of our institution from June 24, 2020 to July 24, 2020. Participants were tested with a wearable dynamic ECG recorder and 12-lead ECG in a supine, an upright position and after exercises for 60 s.

Results
Of the 114 subjects enrolled in the study, 61 had normal sinus rhythm and 53 had AF. The number of cases that could not be determined by the wristband of dynamic ECG recorder was two, one and one respectively. Case results that were not clinically objective were defined as false-negative or false-positive. Results for diagnostic accuracy, sensitivity, and specificity tested by wearable dynamic ECG recorders in a supine position were 94.74% (95% CI% 88.76–97.80%), 88.68% (95% CI 77.06–95.07%), and 100% (95% CI 92.91–100%), respectively. Meanwhile, the diagnostic accuracy, sensitivity and specificity in an upright position were 97.37% (95% CI 92.21–99.44%), 94.34% (95% CI 84.03–98.65%), and 100% (95% CI 92.91–100%), respectively. Similar results as those of the upright position were obtained after exercise.

Conclusion
The widely accessible wearable dynamic ECG recorder integrated with an AI algorithm can efficiently detect AF in different postures and after exercises. As such, this tool holds great promise as a useful and user-friendly screening method for timely AF diagnosis in at-risk individuals.