Search

S100A8/A9 is a proinflammatory protein and plays an essential role in the pathogenesis of myelodysplastic syndromes (MDS) via the S100A8/A9-Toll-like receptors axis. While S100A8/A9 levels have been used as biomarkers in many inflammatory diseases, their clinical relevance has not been conclusively resolved in MDS. To address this, we used an enzyme-linked immunosorbent assay to quantify S100A8/A9 heterodimers in bone marrow (BM) plasma from 215 MDS patients and compared S100A8/A9 levels across patients with various disease risks and genotypes. S100A8/A9 levels correlated with ASXL1 variant allele frequencies significantly. Moreover, mutant ASXL1 with concurrent RUNX1, STAG2, ZRSR2, or EZH2 mutations was associated with higher S100A8/A9 levels. We further showed that higher S100A8/A9 independently predicted inferior leukemia-free survival and overall survival in MDS patients, irrespective of age, Revised International Prognostic Scoring System subgroups, and known detrimental mutations. Lastly, through deep-sequenced transcriptomic analysis, we demonstrated that higher S100A8/A9 in the BM intimated a perturbed microenvironment with enhanced myeloid-derived suppressor cell-mediated tumor immune escape signal, altered metabolism, and impairment in the functions and quantities of CD8+ T cells and NK cells. S100A8/A9 in the BM microenvironment may be a potential biomarker in the prognostication of MDS and target for novel therapy.

Myelodysplastic syndromes (MDS) are a group of clinically and genetically diverse diseases that impose patients with an increased risk of leukemic transformation. While MDS is a disease of the elderly, the interplay between aging and molecular profiles is not fully understood, especially in the Asian population. Thus, we compared the genetic landscape between younger and older patients in a cohort of 698 patients with primary MDS to advance our understanding of the distinct pathogenesis and different survival impacts of gene mutations in MDS according to age. We found that the average mutation number was higher in the older patients than younger ones. The younger patients had more WT1 and CBL mutations, but less mutated ASXL1, DNMT3A, TET2, SF3B1, SRSF2, STAG2, and TP53 than the older patients. In multivariable survival analysis, RUNX1 mutations with higher variant allele frequency (VAF) and U2AF1 and TP53 mutations were independent poor prognostic indicators in the younger patients, whereas DNMT3A and IDH2 mutations with higher VAF and TP53 mutations conferred inferior outcomes in the older patients. In conclusion, we demonstrated the distinct genetic landscape between younger and older patients with MDS and suggested that mutations impact survival in an age-depended manner.

The S100 family proteins are involved in a variety of important biological processes, most notably immune and inflammatory responses. Their dysregulation also plays a role in the pathogenesis of human cancers. S100A4, also known as metastasin, has long been regarded as a biological marker in tumor progression and metastasis in multiple solid cancers, but its clinical significance in acute myeloid leukemia (AML) has not been extensively studied.We retrospectively studied the association between S100A4 gene expression and the clinical characteristics, mutational and transcriptomic profiles of 227 AML patients treated with standard intensive chemotherapy. Genetic mutations of myeloid disease associated genes were analyzed by Sanger sequencing. Microarray-based transcriptomic gene expression profiling was performed on archived bone marrow mononuclear cells. Bioinformatic analyses, including differential gene expression and gene set enrichment analysis, were conducted to delineate the underlying pathogenic mechanisms.Higher S100A4 expression was associated with older age, monocytic differentiation of leukemic cells, and adverse clinical outcome. S100A4 high-expressors had inferior overall survival and disease-free survival; this finding could be validated in the TCGA AML cohort (both the microarray and RNA-seq platforms). Multivariate Cox regression analysis supported S100A4 as an independent prognostic factor. Bioinformatic analysis showed that AML with higher S100A4 expression was enriched for the interferon, NLRP3 inflammasome, and epithelial-mesenchymal transition pathways.This study provides evidence that S100A4 overexpression serves as a poor prognostic biomarker in AML, holds potential to guide treatment planning in the clinic, and indicates novel therapeutic directions.

Increasing evidence supports the role of the immune microenvironment and associated signalling in the pathogenesis of myelodysplastic syndromes (MDS). Nevertheless, the clinical relevancy of immune signals in patients with MDS remains elusive. To address this, we used single-sample gene-set enrichment analysis to score immune signatures of bone marrow (BM) samples from 176 patients with primary MDS. Enhanced signatures of 'immature dendritic cells' and 'natural killer cells with cluster of differentiation (CD)56bright' were correlated with better overall survival (OS), whilst higher 'CD103+ signature' was associated with reduced survival. An MDS-Immune-Risk (MIR) scoring system was constructed based on the weighted sums derived from Cox regression analysis. High MIR scores were correlated with higher revised International Prognostic Scoring System (IPSS-R) scores and mutations in ASXL transcriptional regulator 1 (ASXL1), Runt-related transcription factor 1 (RUNX1), and tumour protein p53 (TP53). High-score patients had significantly inferior leukaemia-free survival (LFS) and OS than low-score patients. The prognostic significance of MIR scores for survival remained valid across IPSS-R subgroups and was validated in two independent cohorts. Multivariable analysis revealed that a higher MIR score was an independent adverse risk factor for LFS and OS. We further proposed a model with the combination of MIR score and gene mutations to be complementary to IPSS-R for the prognostication of LFS and OS of patients with MDS.

Museum digital collection should explore its past (object digitization), present (cultural relic interpretation) and future (knowledge value-added and management) practices and benefits. Therefore, it needs a new perspective. Its importance and the preservation and reuse of Museum digital resources are worthy of attention. Looking at the development of museums, when modern culture has rapidly progressed from analog to digital media, from atoms to the world of bits, the role of museums in collecting objects has changed accordingly. The technology of information communication will become more important for the creation, sharing and preservation of Museum cultural resources through the reproduction and reproduction of exhibits. Based on the basic concepts of digital collections, this study aims to provide a clear direction for the development of Museum digital collections by clarifying the concept of knowledge added value

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma often with extranodal involvement at diagnosis, and yet how this feature correlates with survival awaits elucidation. To address this issue, a correlative analysis between clinical features of 127 MCL patients and their overall survival (OS) was conducted. In this cohort, the median age at MCL diagnosis was 62 years and 81% were males. Eighty-four percent of patients were Ann Arbor stage 4, and 15% were blastoid variants. In patients with gastrointestinal MCL, approximately 40% had gastric involvement. In treatment, CHOP-based induction chemotherapy was given to 61.1% of patients. One-third of patients undertook autologous stem cell transplant (SCT), and 4.7% had allogeneic SCT. The median OS was 82 months and well-stratified in MIPI risk groups. In the multivariate analysis for OS, blastoid variants and gastric involvement were both independent risk factors whereas auto-SCT had a protective effect. Overall, this study corroborated with the current understandings and international therapeutic standards for MCL. Auto-SCT associated with a better OS while allo-SCT remained an option for blastoid variants and those who failed Auto-SCT. Interestingly, patients with gastric involvement tended to have worse survival, a finding that spawns more studies to investigate the mechanism.

Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given.

Rituximab/bendamustine (RB) and rituximab/ifosfamide/carboplatin/etoposide (R-ICE) are commonly used to treat relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their effectiveness has not been compared in real-world practice. This study evaluated data from DLBCL patients who relapsed after or were refractory to first-line therapy in an electronic health record (EHR)-derived database between 2011 and 2018. One hundred thirty-seven patients using RB and 270 patients using R-ICE were included for analysis. Transplantation after second-line therapy was considered a censored event in the time-to-event analyses. Patients in the RB group were older and had poorer performance status while there were no significant differences in stage, cell of origin, and double-/triple-hit subtypes. Relative to the R-ICE group, the RB group had significantly longer time-to-next-treatment (TTNT) and overall survival (OS). Subgroup analyses revealed that patients who were

Mantle cell lymphoma (MCL) is a B-cell lymphoma featuring an aggressive course and a progressive relapsing pattern. International guidelines recommend early consolidative autologous stem cell transplant (auto-SCT) for eligible patients while reserving allogeneic SCT (allo-SCT) as second-line therapy for refractory cases. Since data describing the implementation of transplants in the Asian population with MCL are limited, we aimed to analyze post-SCT outcomes of 99 MCL patients from the Taiwan Bone Marrow Transplant Registry database. The median age was 56 years, and 11% of the patients had blastoid variant MCL. Ninety-four patients received auto-SCT, while 13 patients received allo-SCT, eight of which received allo-SCT after failing auto-SCT. Before auto-SCT, 52% of the patients were in their first complete remission (CR1). Overall, 37 patients (39%) relapsed after auto-SCT. The median post-auto-SCT progression-free survival and overall survival (OS) were 43.6 months and not reached, respectively. Blastoid variant MCL, transplant not received in CR1, and disease progression within 12 months post-auto-SCT independently predicted inferior OS in multivariate analysis. The median post-allo-SCT OS was 74 months. Two patients (15%) died of MCL recurrence post-allo-SCT. Three patients with refractory diseases were salvaged with ibrutinib or venetoclax to allo-SCT. Treatment strategies incorporating novel agents warrant further optimization.

Background Allogeneic stem cell transplantation (allo-HSCT) is the ultimate cure for acute lymphoblastic leukemia (ALL). Aim This study was performed to compare the outcomes of ALL patients receiving busulfan (Bu) with cyclophosphamide (Cy)-based or total body irradiation (TBI)-based regimen in a Chinese population. Methods We enrolled 224 adult patients with ALL who received allo-HSCT at National Taiwan University Hospital between 1997 and 2016. Results The median age at transplantation was 33 years. Before allo-HSCT, 75.9% of patients attained first or late complete remission. A total of 141 patients (62.9%) received Bu/Cy-based conditioning, either myeloablative (MA) or reduced-intensity stem cell transplantation (RIST), and 83 patients received a TBI-based regimen (MA-TBI). Patients receiving the MA-Bu regimen had longer relapse-free survival (RFS) than those receiving the MA-TBI regimen (median, 24.1 vs. 6.7 months, p = .044). There was no difference in overall survival (OS, MA-Bu vs. MA-TBI vs. RIST-Bu: 39.4 vs. 28.2 vs. 13.1 months, p = .276), treatment-related mortality (TRM), or incidences of grade 3-4 acute graft-versus-host disease (GvHD). Among patients receiving identical GvHD prophylactic regimens, there was no difference between MA-Bu and MA-TBI groups regarding the incidence of grade 3-4 acute GvHD, grade 2-4, and all-grade chronic GvHD. In subgroup analysis, patients receiving oral busulfan had comparable RFS and OS to the intravenous busulfan group (p = .436 and p = .236, respectively), but a higher TRM (25% vs. 9.8%, p = .016). In the multivariable analysis, disease status before allo-HSCT was the only risk factor impacting RFS and OS. Conclusion In summary, patients receiving Bu/Cy-based or TBI-based regimens as conditioning had similar results in terms of OS, TRM, and acute GvHD, whereas the use of myeloablative Bu/Cy resulted in a better RFS. A Bu-based regimen could be an alternative conditioning choice for patients who are ineligible to receive TBI. Prospective and randomized controlled trials are warranted to validate the long-term outcomes.

This study aims to measure the changes in the water literacy of the subjects (N = 620) aged over 18 before and after participating in the water-saving activities. The results showed that there is a significant improvement in the water literacy of the subjects after the water-saving activities but with a medium-small effect size; there is no significant correlation between water knowledge and water attitude before or after the activities. In addition, there is a significant difference in water literacy regarding subjects' background variables, such as age, income, and household water expenses. In other words, the attitude and behavior related to the use of water could be easily influenced by different background variables. Due to the limitation of the museum being the study field, the post-tests were given immediately following the activities, therefore the improvements of the subjects' knowledge and attitudes may not be retained over time. The findings can serve as a reference for the Water Resources Department to promote water conservation education in the future.

Key Points CIBERSORTx analytical approach reveals M0, M2, and eosinophil fractions in the BM to be the most relevant prognostic factors in patients with MDS.High-risk immune cell scores correlate with NF-κB signaling, oxidative stress, and leukemic stem cell signature pathways., Visual Abstract, Aside from cell intrinsic factors such as genetic alterations, immune dysregulation in the bone marrow (BM) microenvironment plays a role in the development and progression of myelodysplastic syndromes (MDS). However, the prognostic implications of various immune cells in patients with MDS remain unclear. We adopted CIBERSORTx to estimate the relative fractions of 22 subtypes of immune cells in the BM of 316 patients with MDS and correlated the results with clinical outcomes. A lower fraction of unpolarized M0 macrophages and higher fractions of M2 macrophages and eosinophils were significantly associated with inferior survival. An immune cell scoring system (ICSS) was constructed based on the proportion of these 3 immune cells in the BM. The ICSS high-risk patients had higher BM blast counts, higher frequencies of poor-risk cytogenetics, and more NPM1, TP53, and WT1 mutations than intermediate- and low-risk patients. The ICSS could stratify patients with MDS into 3 risk groups with distinct leukemia-free survival and overall survival among the total cohort and in the subgroups of patients with lower and higher disease risk based on the revised International Prognostic Scoring System (IPSS-R). The prognostic significance of ICSS was also validated in another independent cohort. Multivariable analysis revealed that ICSS independently predicted prognosis, regardless of age, IPSS-R, and mutation status. Bioinformatic analysis demonstrated a significant correlation between high-risk ICSS and nuclear factor κB signaling, oxidative stress, and leukemic stem cell signature pathways. Further studies investigating the mechanistic insight into the crosstalk between stem cells and immune cells are warranted.

Expression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with RUNX1 mutation, but inversely correlated with t(8;21) and t(15;17) karyotypes. Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance.

Long non-coding RNAs (lncRNAs) have important functions in cancer biology. Among them, lncRNA KIAA0125 is one of the genes proposed to play a critical role in leukaemia stem cell (LSC). In this study, we aimed to investigate the clinical relevance of the expression levels of lncRNA KIAA0125 in myelodysplastic syndromes (MDS), a disease with highly heterogeneous clinical and biological features. Using RNA arrays, we measured the expression of KIAA0125 in 176 primary MDS patients. We found that higher KIAA0125 expression was associated with higher risk MDS, based on the revised International Prognostic Scoring System (IPSS-R), mutations in ASXL1 and NRAS, and predicted poorer overall survival (OS) and leukaemia-free survival (LFS). Multivariate analysis revealed that higher KIAA0125 expression was an independent, unfavourable prognostic factor for OS and LFS, irrespective of IPSS-R and mutation status. Further global gene expression profile analysis suggested a close association of higher KIAA0125 expressions with LSC signatures. The expression of KIAA0125 may be a potential biomarker to guide the treatment choice in MDS patients, especially those with lower risk subtypes, in whom palliative treatment is usually used.

Expression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study was aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with FLT3-ITD, RUNX1, and DNMT3A mutations, and M1 subtype by the French-American-British classification, but inversely correlated with t(8;21) and t(15;17). Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance.

Background: Far-infrared radiation (FIR) therapy improves vessel dilation, circulation, vessel endothelial function, and angiogenesis and reduces atherosclerosis. However, evidence of FIR therapy’s effects on foot circulation among diabetic patients undergoing hemodialysis is scarce. Aim: To determine whether FIR therapy improves foot circulation in diabetic patients undergoing hemodialysis. Design: Quasi-experimental. Methods: In June to November 2017, diabetic patients undergoing hemodialysis ( N = 58) at a hemodialysis center in northern Taiwan were divided into two groups: the experimental group ( n = 31) received FIR therapy to the bilateral dorsalis pedis artery (40 min/session, 3 times/week for 6 months) and the control group ( n = 27) received conventional dialysis care. Paired t test, independent samples t test, two-proportion Z test, and repeated-measures analysis of covariance were performed to compare changes from baseline to the end of the 6-month intervention between the groups. Results: Significant positive effects of FIR therapy on temperature, pulse, and blood flow of the dorsalis pedis artery were observed. Sensitivity to pain, tactility, and pressure also improved significantly in the experimental group. The Edinburgh Claudication Questionnaire revealed that the experimental group had reductions in subjective experiences of soreness, tingling, and coldness in the feet. Conclusion: The findings of significant improvements to objective and subjective measures of blood flow and neural function in the experimental group indicate that FIR therapy improves blood circulation to the feet. This therapy thus has great potential to be an effective adjuvant treatment for patients with diabetes mellitus undergoing hemodialysis.

RUNX1 is a member of the core-binding factor family of transcription factors and is imperative for establishing definitive haematopoiesis. Mutated RUNX1 is an adverse risk factor for myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Meanwhile, high expression of RUNX1 is correlated with dismal prognosis in cytogenetically normal AML patients and critical for maintaining leukemic stem cells across AML genetic subgroups. However, the clinical relevancy of RUNX1 expression in MDS patients remains elusive. This study aimed to investigate the prognostic and biologic impacts of RUNX1 expression in MDS patients. We recruited 341 primary MDS patients who had enough bone marrow (BM) samples for RNA and next-generation sequencing. We first examined the difference in RUNX1 expression among patients with wild RUNX1 and N-terminal or C-terminal RUNX1 mutation. Among the 341 patients, 54 (15.8%) harboured RUNX1 mutation, 15 (27.8%) in N-terminal and 39 (72.2%), C-terminal. Patients with C-terminal RUNX1 mutant had higher RUNX1 expression than those with N-terminal RUNX1 mutant or wild RUNX1 (p Regarding survival, we first examined the impact of RUNX1 mutation on survival in this cohort. As expected, patients with mutated RUNX1 had significantly inferior leukaemia-free survival (LFS) and overall survival (OS) than those with unmutated RUNX1 (p=0.007, and p=0.008, respectively). We then explored the effects of RUNX1 expression on patients' survival. Patients with higher RUNX1 expression had significantly inferior LFS and OS than those with lower expression (both p Figure 1 Figure 1. Disclosures Tien: AbbVie: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria. Chou: Abbvie: Honoraria, Other: Advisory Board, Research Funding; Celgene: Honoraria, Other: Advisory Board, Research Funding; IQVIA: Honoraria, Other: Advisory Board; Pfizer: Honoraria, Other: Advisory Board; Novartis: Honoraria, Other: Advisory Board; Bristol Myers Squibb: Honoraria, Research Funding; Kirin: Honoraria, Research Funding.

Background & Purpose The clinical course of mantle cell lymphoma (MCL) is often inflicted with tumor recurrence even though front-line autologous stem cell transplantation (ASCT) is the current standard of care. To elucidate the mechanism of post-transplant recurrence, this study aimed to interrogate the minimal residual disease (MRD) of MCL in the autologous grafts. Materials & Methods Paired samples of 17 MCL patients' lymphoma diagnostic FFPE specimens were analyzed in parallel with their harvested autologous stem cell grafts. Extracted genomic DNA was subjected to LymphoTrackⓇ Dx IGH/IGK assay coupled with Illumina MiSeq sequencer to characterize the post-recombination immunoglobulin VDJ sequences. Positivity of MRD was defined for any identical sequences identified both in the diagnostic FFPE and in the autologous graft DNA. As the control for recombined VDJ protein motif analysis, diagnostic FFPE samples from 23 patients with diffuse large B cell lymphoma (DLBCL) were analyzed with the same platform. Results Of the 17 patients undertaking autologous stem cell harvest, 11 patients achieved complete response and 6 were in partial response before stem cell harvest. Sixteen of these actually underwent transplantation while one died of disease before transplantation. MRD was detected via next-generation sequencing (NGS) in 5 patients' autologous grafts with variable MRD loads and recombined VDJ stereotypes (Table 1). VH3-21 was the most prominent stereotype (41%), followed by VH4-59 (14%). The median somatic hypermutation rate was 0.88% (range 0 - 5.17%). Interestingly, a 46-amino-acid domain in recombined VDJ sequences, which was hydroxyl and amine group-rich, differed between MCL and DLBCL: hydrophilic amino acids were enriched in 6 positions of this domain in MCL (p1%) correlated with shorter post-ASCT PFS and OS than those without MRD (medians, 1.9 months vs 27 months (p=0.024) in Figure 1c, and 11.9 months vs 66.8 months (p=0.001) in Figure 1d, respectively). Conclusions Identification of MRD in autologous grafts by deep-sequencing VDJ recombination helped stratify MCL patients' post-ASCT outcomes. Higher MRD loads correlated with inferior post-ASCT PFS and OS. The implication of recombined VDJ stereotypes and their impact on ASCT outcomes warrants further investigation. Disclosures Ko: Roche: Honoraria.

Background: Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSC) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSC were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions on patients with MDS, a disorder arising from hematopoietic stem cells, remains unclear. Methods: We analysed expression profile of the 17 stemness-related genes in primary MDS patients and identified expressions of 4 genes were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the four genes expressions and explored its clinical implications in MDS patients. Findings: Higher LSC4 scores were associated with higher revised international prognostic scoring system (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, ZRSR2, U2AF1, SRSF2, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS) which was also confirmed in two independent validation cohorts. Subgroups analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS. Interpretation: LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given. Funding: The study was supported by grants from Ministry of Health and Welfare, and Science and Technology, Taiwan. Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: This study was approved by the Institutional Review Board of the NTUH.

This study investigated the college students (N = 725) and high school students (N = 585) that participated in the National Energy Technology Creative Contest (NETCC) of Taiwan. AMOS analysis was performed to establish a model of students’ performances in creative contests and t-test was conducted to analyze and compare the differences in variables between the two groups of students in the model. The findings of this study are as follows: (1) the research model fits the model of college and high school students’ performances in creative contests; (2) for college students (Model 1), their performances in creative contests are directly affected by team composition and knowledge variables, and team composition variables can also directly affect knowledge variables, (3) for high school students (Model 2), their performances in creative contest are directly affected by team composition and knowledge variables, but there is no direct correlation between team composition variables and knowledge variables, (4) comparison and analysis of the mean of the variables that affect the students’ performances in creative contests show that, for most variables, the mean of high school students is significantly higher than that of college students.

The allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is viewed as the ultimate cure for acute lymphoblastic leukemia (ALL). An essential component of allo-HSCT is the conditioning regimen administered before the hematopoietic stem-cell infusion. This study is aimed to compare outcomes of ALL patients receiving either a busulfan with cyclophosphamide (BuCy) or a total body irradiation(TBI)-based regimen. We retrospectively analyzed data from National Taiwan University Hospital institute registry. We enrolled 224 adult patients with ALL who received allo-HSCT between 1997 and 2016 and compared outcomes of patients receiving either a BuCy-based or a TBI-based regimen. There were more B-cell ALL than T-cell ALL (67.8% vs 32.2%). A total of 41 patients (22.5%) carried the Philadelphia chromosome (Ph) while 38 patients (20.9%) carried complex karyotype. Before the allo-HSCT, 164 (73.2%) patients achieved first or late complete remission (CR). The main source of stem-cell was from peripheral blood (71%), followed by bone marrow (22.3%). Siblings comprised 54.9% of the donors. A total of 141 patients (63%) received BuCy-based conditioning, either myeloablative (MA) or reduced intensity stem cell transplantation (RIST) and 83 patients (37%) received TBI-based regimen. The mean dose of stem cell was 4.96 ± 2.42 × 106/Kg CD34+ cells. We use cyclosporine and mycophenolate mofetil for prophylaxis of graft-versus-host disease (GvHD). In results, patients received BuCy-based regimen performed as well as TBI-based group in terms of 5-year overall survival (47.5% vs 37.3%, p=0.115). As to 5-year relapse-free survival (RFS), BuCy group had slightly better result, especially the group received myeloablative conditioning (MA, Bu-based vs. MA, TBI-based, p=0.059), albeit the p value didni¦t reach significance, the curves went on departing ways. In this study, all regimen groups yielded similar treatment-related mortality (TRM), (MA, Bu-based vs RIST, Bu-based vs MA, TBI-based: 17% vs 10.9% vs 21.7%, p=0.308) and incidences of grade 3-4 acute GvHD at day+100, (p=0.445). Further, in patients with extramedullary disease, there was no difference among groups; and interestingly, BuCy group with MA conditioning seemed to yield better result than TBI group (p=0.072). By multi-variate analysis, disease status before allo-HSCT is the only risk factor impacting OS and RFS. In conclusion, patients received BuCy-based regimen or TBI-based regimen as conditioning had similar results in terms of OS, RFS, TRM, and GvHD.

Leukemic stem cells (LSCs) possess biological properties shared with normal hematopoietic stem cells. They are responsible for chemoresistance and relapse in acute myeloid leukemia (AML). Although myelodysplastic syndrome (MDS) has traditionally been regarded as a "hematopoietic stem cell disorder", the clinical and biological impact of LSCs on MDS patients are not well defined. To address this question, we used the Affymetrix HTA 2.0 microarray platform to profile 16 out of the 17 recently reported stemness genes (one of them, the ARHGAP22 gene was not included in our array) in our 160 adult primary MDS patients. The diagnoses were based on the 2016 World Health Organization (WHO) classification. Patients with antecedent chemotherapy or hematologic malignancies were excluded. Forty-one (25.6%) patients had MDS with single lineage dysplasia (MDS-SLD), 20 (12.5%) had MDS with ring sideroblasts (MDS-RS), 31 (19.4%) had MDS with multilineage dysplasia (MDS-MLD), 32 (20%) had MDS with excess blasts-1 (MDS-EB1) and 36 (22.5%), MDS-EB2. The risk distribution of the cohort was very-high risk, 15.3%; high risk, 21.3%; intermediate risk, 24.7%; low risk 34.7%; and very-low risk 4% according to the revised international prognosis scoring system (IPSS-R). We identified 4 genes (LAPTM4B, NGFRAP1, NYNRIN, and EMP1) whose expression levels were significantly correlated with overall survival (OS). An LSC4 score (0.731 x LAPTM4B - 1.259 x NGFRAP1 + 0.304 x NYNRIN + 0.231 x EMP1) was constructed based on the weighted sums derived from Cox regression analysis. Higher LSC4 scores were associated with higher IPSS-R scores, complex cytogenetics, and higher incidences of mutations of RUNX1, ASXL1, TP53, SRSF2 and ZRSR2. High-score patients had significantly higher 3-year AML transformation rate (36.3% vs 11.3%, P Disclosures No relevant conflicts of interest to declare.

For performance-based seismic engineering of buildings, the direct displacement-based seismic design method is different from the coefficient method used in FEMA-273 and the capacity spectrum method adopted in ATC-40. The method not only is a linear static procedure but also is applied to the design of new constructions. This paper concerns with experimental studies on the accuracy of the direct displacement-based design procedure. Experimental results of three reinforced concrete (RC) columns designed by the displacement procedure are presented and discussed through pseudo-dynamic tests and cyclic loading tests. From the tests, it is shown that the stiffness degrading factor of RC columns plays a key role. The direct displacement-based seismic design method can reliably capture the maximum displacement demand of the test RC columns if the stiffness degrading factor adopted in the displacement design method for RC material is adequate.

Recently, metal-oxide semiconductor-based gas sensors have gotten a great attention due to their special advantages, such as low cost, high performance and easily fabricated. ZnO has been extensively studied, because it can be applied to sense various gases. One-dimensional ZnO nanostructures can enhance the sensing performance. The vertical nanowire array is a common structure for ZnO nanowire-based gas sensor. However, the seed layer under the nanowire array reduces the sensing capability. Therefore, in this study, the gas sensing devices were fabricated by the arrangement of nanowires between the electrodes. ZnO nanowires were synthesized on the ZnO seed layer by hydrothermal method. The alternating current electrical field was used to align ZnO nanowires of different lengths between the electrodes. For gas sensing application, two types of the nanowire structured devices were used to detect CO. The results show that a flat surface and small grain of seed layer was received by annealing at 300℃, and it can be used to fabricate ZnO nanowires with small fluctuation in length and width by hydrothermal method. ZnO nanowires had the highest aspect ratio when the concentration of precursors was 0.04M. The length of nanowires increased by adding an appropriate concentration of Polyetherimide (PEI). In the process of ZnO nanowires aligment by dielectrophoresis method, the parallel and crossed ZnO nanowire-based devices were achieved by adjusting the frequency and the peak-to-peak voltage of alternating current electrical field. For the CO sensing , the sensing sensitivity and stability of the crossed structure nanowires-based devices were enhanced after annealing. The sensing sensitivity and limit-of-detection of the crossed nanowire-based devices were better than the parallel nanowire-based ones due to the potential barrier modulation at the nanojunctions between two nanowires.

Le compose (1) du titre cristallise dans le systeme orthorhombique, groupe d'espace P2 1 2 1 2 1 et sa structure est affinee jusqu'a R=0,038. Le compose (2) cristallise dans le systeme monoclinique, groupe d'espace P2 1 /n avec R=0,041