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Abstract Background Military personnel face an increased risk of developing mental disorders owing to the stressful environments they encounter. Effective stress management strategies are crucial to mitigate this risk. Mindfulness training (MT) is promising as a stress management approach in such demanding settings. This study uses a quantitative approach to investigate the impact of MT on the relationship between the autonomic nervous system (ANS) and emotional regulation. Methods The study evaluated the effectiveness of MT in reducing stress among 86 military personnel. Participants were divided into two groups: MT (n = 42) and non-MT (n = 38). The study compared the two groups using measures of heart rate variability (HRV), a reliable indicator of ANS activity. Results The MT group exhibited a significant increase in HRV (14.4%, p = 0.001) and alpha asymmetry (AA) in the frontal lobe (45.7%, p < 0.001) compared to the non-MT group. Notably, the MT group achieved significantly higher scores on the parachute landing fall (PLF) training performance (p < 0.001). These improvements in HRV, AA, and PLF performance were strongly correlated. Furthermore, AA fully mediated the relationship between HRV and PLF training performance. Conclusions The findings suggest that MT has a positive impact on stress resilience, potentially by mitigating anxiety and attention deficits induced by extreme stressors. These positive effects are facilitated by concurrent modulation of the frontal cortex and autonomic nervous system. Our findings provide insight into the neural mechanisms behind MT-induced stress reduction from the perspective of neuromodulation.

ABSTRACT Background The prognostic significance of extranodal sites in stage IV diffuse large B‐cell lymphoma (DLBCL) remains uncertain, making it challenging to select appropriate treatment strategies for individual patients. In this study, we aimed to evaluate the influence of different extranodal sites on prognosis in young patients with stage IV DLBCL who achieved complete remission (CR) following initial chemo‐immunotherapy and to explore the potential of autologous hematopoietic stem cell transplantation (ASCT) as a consolidation treatment for specific patient subgroups. Methods We retrospectively reviewed data from 119 patients with DLBCL aged

IntroductionMonomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, aggressive subtype of primary gastrointestinal T-cell lymphoma. Owing to the absence of symptoms characteristic of MEITL, diagnosis can be challenging, and the low response rate to conventional chemotherapy leads to an abysmal prognosis. This study aimed to define the clinicopathologic characteristics of MEITL in Korea, evaluate the clinical outcomes of intensive chemotherapy with and without hematopoietic stem cell transplantation (HSCT), and explore prognostic factors.MethodsThis single-center retrospective study examined the clinical data of 35 patients diagnosed with MEITL at Seoul St. Mary’s Hospital from May 2012 to May 2023.ResultsWe included 22 men and 13 women (median age: 59 years; range: 37–79 years). Many patients exhibited acute abdominal pain (n=23, 65.7%) related to bowel perforation (n=21, 60.0%). Most patients (30/35, 85.7%) underwent surgical intervention to diagnose MEITL, whereas only five were diagnosed via endoscopic evaluation. Of the 32 patients receiving first-line therapy, 4 died before assessment, 10 achieved a complete response (CR), 6 had a relapse, and 18 exhibited progressive disease (PD). Seven of 10 patients received upfront HSCT, either autologous (auto-HSCT, n=4) or allogeneic (allo-HSCT, n=3). All four patients on auto-HSCT died after relapse. All three patients who received allo-HSCT maintained a CR by the final follow-up. Three of 6 patients who relapsed and 13 of 18 exhibiting PD received salvage therapy; one patient on salvage auto-HSCT with cytokine-induced killer cell infusion has survived progression free. Salvage allo-HSCT was performed on 6 of 16 patients; among them, 2 achieved a CR, 2 died after relapse, and 2 died owing to septic shock while maintaining a CR. The remaining patients, who received salvage therapy without HSCT, mostly died owing to PD. The median overall survival was 12.1 months, and the median follow-up was 33.2 months. The 1- and 5-year overall survival was 50.9% and 13.3%, respectively.DiscussionMEITL is an aggressive disease resistant to conventional therapy. Therefore, intensive chemotherapy followed by upfront allo-HSCT should be considered upon diagnosis. These findings underscore the need for novel therapeutic strategies and further investigation into optimizing treatment protocols for MEITL.

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Abstract Early diagnosis and following management are important determinants of the prognosis of multiple myeloma (MM). However, screening for MM is not routinely performed because it is rare disease. In this study, we evaluated the association of prior disease condition and socioeconomic status (SES) with MM diagnosis and developed a simple predictive model that can identify patients at high risk of developing MM who may need screening using nationwide database from South Korea. According to multivariate logistic regression analysis, eight prior disease conditions and SES before diagnosis were shown to be predictors of MM development and selected for score development. Total prediction scores were categorized into four groups: patients without any risk (≤ 0) intermediate-1 (0.5–9), intermediate-2 (9–14), and high risk (> 14). The odds ratios for developing MM in the intermediate-1, intermediate-2, and high-risk groups were 1.29, 3.07, and 4.62, respectively. The association of prior disease conditions and SES with MM diagnosis were demonstrated and the simple scoring system to predict the MM risk was developed. This scoring system is also provided by web-based application and could be a useful tool to support clinicians in identifying potential candidates for MM screening.

Abstract The cell-derived vesicles (CDVs) obtained using a proprietary extrusion process are the foundation of BioDrone platform technology. With superior productivity and versatility, this technology has garnered increasing attention in broad applications, particularly as a drug delivery vehicle. Previously, we showed that CDVs exhibited varying levels of expression for tetraspanin and organelle membrane markers while revealing no discernible differences in physical characteristics compared to naturally produced extracellular vesicles (EVs). To further understand and utilize the therapeutic potentials of CDVs, a more comprehensive study of membrane protein profiles is necessary. In addition, it is crucial to validate that the CDVs produced from extrusion are indeed intact lipid vesicles rather than other impurities. Here, we produced multiple batches of CDVs and EVs from HEK293 cells. CDVs and EVs were subjected to the same purification processes for subsequent proteome and particle analyses. The proteome analyses revealed unique proteome signatures between CDVs, EVs, and parental cells. Extensive proteome analyses identified the nine most prominent membrane markers that are abundant in CDVs compared to cells and EVs. Subsequent western blotting and nanoparticle flow cytometry analyses confirmed that CD63, lysosome-associated membrane glycoprotein 1 (LAMP1), and nicastrin (NCSTN) are highly enriched in CDVs, whereas CD81, CD9, and prostaglandin F2 receptor negative regulator (PTGFRN) are more abundant in EVs. This highlights the unique membrane composition and marker signature of CDVs that are distinct from EVs. Lastly, we demonstrated that more than 90% of the CDVs are genuine lipid vesicles by combining two different classes of vesicle labeling dyes and detergents to disrupt lipid membranes. This indicates that our proprietary extrusion technology is highly compatible with other well-characterized EV production methods. The robust CDV markers identified in this study will also facilitate the engineering of CDVs to achieve enhanced therapeutic effects or tissue-selective cargo delivery.

Background/Objectives: This study aimed to develop a fully validated HPLC-MS/MS method for quantifying total and unbound lenalidomide concentrations in human plasma. Methods: Unbound concentrations were measured using plasma ultrafiltrate prepared with Amicon® Centrifugal Filters. Lenalidomide and lenalidomide-d5 (internal standard) were extracted from 50 μL of human plasma using liquid–liquid extraction. Chromatography was conducted with a Halo® C18 column using 0.1% formic acid and methanol (20:80, v/v) as the mobile phase. The mass spectrometer was operated in a positive ion mode with an electrospray ionization interface and multiple reaction monitoring modes. Results: Calibration curves were linear over the range of 5 to 1000 ng/mL (r2 > 0.996) for both the total and unbound lenalidomide. For total lenalidomide concentrations, between-run precision (coefficients of variation) and accuracy were 1.70–7.65% and 94.45–101.10%, respectively. For unbound concentrations, inter-day precision and accuracy were 1.98–10.55% and 93.95–98.48%, respectively. Conclusions: We developed a highly reproducible, sensitive, and efficient bioanalytical method using a smaller volume of plasma sample (50 μL) with a relatively short run time (2.5 min). The proposed analytical method was successfully applied to measure total and unbound lenalidomide concentrations at various time points in multiple myeloma patients with renal impairment.

Abstract To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen’s efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE’s that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

PURPOSEAutologous hematopoietic stem cell transplantation (ASCT) has been introduced as a standard treatment for newly diagnosed multiple myeloma (NDMM) following novel agent-based induction chemotherapy. This study investigated whether pre-ASCT low muscle mass evaluated using the paraspinal muscle index (PMI) at the 12th thoracic vertebra (T12) level is a reliable prognostic marker in NDMM after chemotherapy.METHODSA multi-center registry database was retrospectively analyzed. Between 2009 and 2020, 190 patients with chest computed tomography images underwent frontline ASCT following induction therapy. The PMI was defined as the value of the paraspinal muscle area at the T12 level divided by the square of the patient’s height. The cut-off value indicating a low muscle mass was sex-specific, using the lowest quintiles.RESULTSOf the 190 patients, 38 (20%) were in the low muscle mass group. The low muscle mass group had a lower 4-year overall survival (OS) rate than the non-low muscle mass group (68.5% vs. 81.2%; P = 0.074). The median progression-free survival (PFS) in the low muscle mass group was significantly shorter compared with the non-low muscle mass group (23.3 months vs. 29.2 months; P = 0.029). The cumulative incidence of transplant-related mortality (TRM) was significantly higher in the low muscle mass group than in the non-low muscle mass group (4-year probability of TRM incidence, 10.6% vs. 0.7%; P < 0.001). In contrast, no significant difference in the cumulative incidence of disease progression was found between the two groups. Multivariate analysis revealed that low muscle mass was associated with significant negative outcomes for OS [(hazard ratio (HR): 2.14; P = 0.047], PFS (HR: 1.78; P = 0.012), and TRM (HR: 12.05; P = 0.025).CONCLUSIONParaspinal muscle mass may have a prognostic role in NDMM patients who undergo ASCT. Patients with low paraspinal muscle mass have lower survival outcomes compared to non-low muscle mass group.

Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease. We analyzed 78 patients with biopsy-confirmed hepatic GVHD (n = 38) or autoimmune liver disease (n = 40) between 2016 and 2021. The cholestatic variant was defined by an R-value < 2.0, based on the ratio of alanine aminotransferase to alkaline phosphatase. The primary outcome was the biochemical response at 4 (early) and 8–12 (late) weeks after corticosteroid treatment. In hepatic GVHD patients, the hepatitic variant (n = 19) showed greater CD3+ T-cell infiltration than the cholestatic variant (n = 19; p < 0.001). No significant differences were observed in the infiltration of CD20+, CD38+, or CD68+ cells. The hepatitic variant had significantly better early and late responses and higher liver-related event-free survival than the cholestatic variants (p < 0.05). Concerning autoimmune liver diseases, the autoimmune hepatitis (AIH) group had significantly more portal T-cell infiltration and better treatment responses than the primary biliary cholangitis (PBC) group. In conclusion, higher portal T-cell infiltration may be associated with better clinical outcomes in patients with hepatic GVHD. Additionally, this study highlights similarities in portal T-cell infiltration and treatment response patterns between AIH and the hepatitic variant, as well as PBC and the cholestatic variant.

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The influence of carbide precipitation on the mechanical properties of hot work tool steels was investigated in this study. Compared to the commercial H13 hot work tool steel, the KMoW and RW steels containing W exhibited a reduced high-temperature softening and an enhanced thermal fatigue resistance during long-term aging. These improvements can be attributed to the increased structural and chemical stability of V-rich MC carbides. The increased (W + Mo)/(V + Fe) atomic ratios at MC metallic sites increased their coherency as well as reduced the driving force required for the precipitation of Cr-rich carbides. These findings suggest that the addition of W effectively improves the heat-checking resistance and mechanical properties of hot work tool steels.

Abstract Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens—bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04–0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.

Abstract We study whether deep neural network based algorithm can filter out mammography phantom images that will pass or fail. With 543 phantom images generated from a mammography unit, we created VGG16 based phantom shape scoring models (multi-and binary-class classifiers). Using these models we designed filtering algorithms that can filter failed or passed phantom images. 61 phantom images obtained from two different medical institutions were used for external validation. The performances of the scoring models show an F1-score of 0.69 (95% confidence interval (CI) 0.65, 0.72) for multi-class classifiers and an F1-score of 0.93 (95% CI 0.92, 0.95) and area under the receiver operating characteristic curve of 0.97 (95% CI 0.96, 0.98) for binary-class classifiers. A total of 42 of the 61 phantom images (69%) were filtered by the filtering algorithms without further need for assessment from a human observer. This study demonstrated the potential to reduce the human workload from mammographic phantom interpretation using the deep neural network based algorithm.

We report that the corrosion resistance of Mg is significantly improved by adding 0.05wt% Sc. Corrosion rates evaluated from weight loss values after room-temperature immersion in 0.6 M NaCl solution for two weeks were 0.27 and 4.0 mm y−1 for the high-purity Mg samples with and without microalloyed 0.05wt% Sc, respectively. The beneficial effect of Sc microalloying on the corrosion resistance of Mg is discussed in connection with Sc-induced microstructural modifications.

Multiple myeloma, which is a proliferative disease of plasma cells that originate from a single clone, is the second most common hematologic malignancy following non-Hodgkin lymphoma. In the past, its diagnosis was made based on clinical findings (so-called “CRAB”) and a skeletal survey using radiographs. However, since the implementation of the International Myeloma Working Group’s revised guideline regarding the radiologic diagnosis of multiple myeloma, whole-body (WB) MRI has emerged to play a central role in the early diagnosis of multiple myeloma. Diffusion-weighted imaging and fat quantification using Dixon methods enable treatment response assessment by MRI. In keeping with the trend, a multi-institutional and multidisciplinary consensus for standardized image acquisition and reporting known as the Myeloma Response Assessment and Diagnostic System (MY-RADS) has recently been proposed. This review aims to describe the clinical application of WB-MRI based on MYRADS in multiple myeloma, discuss its limitations, and suggest future directions for improvement.

IntroductionIntensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking.MethodsTherefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined.ResultsAll GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival.DiscussionThis study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.

Aplastic anemia (AA) is a lethal hematological disorder; however, its pathogenesis is not fully understood. Although immunosuppressive therapy (IST) is a major treatment option for AA, one-third of patients do not respond to IST and its resistance mechanism remains elusive. To understand AA pathogenesis and IST resistance, we performed single-cell RNA sequencing (scRNA-seq) of bone marrow (BM) from healthy controls and patients with AA at diagnosis. We found that CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells were significantly depleted in AA, which suggests that the depletion of CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells might be one of the major mechanisms for AA pathogenesis related with BM-cell hypoplasia. More importantly, we observed the significant enrichment of CD8+ T cells and T cell–activating intercellular interactions in IST responders, indicating the association between the expansion and activation of T cells and the positive response of IST in AA. Taken together, our findings represent a valuable resource offering novel insights into the cellular heterogeneity in the BM of AA and reveal potential biomarkers for IST, building the foundation for future precision therapies in AA.

Long-term hepatic damage is associated with human morbidity and mortality owing to numerous pathogenic factors. A variety of studies have focused on improving liver health using natural products and herbal medicines. We aimed to investigate the effect of enzyme-treated Zizania latifolia ethanol extract (ETZL), which increases the content of tricin via enzymatic hydrolysis, for 8 weeks on liver-related outcomes, lipid metabolism, antioxidant activity, and fatigue compared to a placebo. Healthy Korean adult males aged 19–60 years were randomized into ETZL treatment and placebo groups, and alcohol consumption was 24.96 and 28.64 units/week, respectively. Alanine transaminase, a blood marker associated with liver cell injury, significantly decreased after 8 weeks compared to the baseline in the ETZL treatment group (p = 0.004). After 8 weeks, the treatment group showed significant changes in the levels of high-density lipoprotein and hepatic steatosis index compared to the baseline (p = 0.028 and p = 0.004, respectively). ETZL treatment tended to reduce antioxidant-activity-related factors, total antioxidant status, and malondialdehyde, but there was no significant difference. In the multidimensional fatigue scale, ETZL treatment showed a significant reduction in general fatigue and total-fatigue-related values after 8 weeks compared to the baseline (p = 0.012 and p = 0.032, respectively). Taken together, the 8-week treatment of enzyme-treated Zizania latifolia ethanol extract demonstrated positive effects on liver-related outcomes, lipid metabolism, and mental fatigue without adverse effects on safety-related parameters.

Abstract Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p

Abstract Membrane‐bound vesicles such as extracellular vesicles (EVs) can function as biochemical effectors on target cells. Docking of the vesicles onto recipient plasma membranes depends on their interaction with cell‐surface proteins, but a generalizable technique that can quantitatively observe these vesicle–protein interactions (VPIs) is lacking. Here, we describe a fluorescence microscopy that measures VPIs between single vesicles and cell‐surface proteins, either in a surface‐tethered or in a membrane‐embedded state. By employing cell‐derived vesicles (CDVs) and intercellular adhesion molecule‐1 (ICAM‐1) as a model system, we found that integrin‐driven VPIs exhibit distinct modes of affinity depending on vesicle origin. Controlling the surface density of proteins also revealed a strong support from a tetraspanin protein CD9, with a critical dependence on molecular proximity. An adsorption model accounting for multiple protein molecules was developed and captured the features of density‐dependent cooperativity. We expect that VPI imaging will be a useful tool to dissect the molecular mechanisms of vesicle adhesion and uptake, and to guide the development of therapeutic vesicles.

Background: Blinatumomab showed a higher complete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Objectives: We tried to analyze the outcome of blinatumomab compared with the real-world historical data. We expected superior outcome of blinatumomab compared with historical conventional chemotherapy. Design: We conducted a retrospective study using real-world data in the Catholic Hematology Hospital. Methods: Total 197 consecutive cases of R/R BCP-ALL were treated with conventional chemotherapy ( n = 113) or blinatumomab, which was available since late 2016 ( n = 84). Patients who achieved CR underwent allo-HCT if donor was available. We conducted a propensity score–matched cohort analysis using 5 criteria of age, CR duration, cytogenetics, previous allo-HCT, and salvage lines between historical group and blinatumomab. Results: Each cohort consisted of 52 patients. In blinatumomab group, CR rate was higher (80.8% versus 53.8%, p = 0.006) and more patients proceeded to allo-HCT (80.8% versus 46.2%, p

We aimed to analyze the increase in the sleep-promoting effects based on the mixed ratio of botanical extracts, Ziziphus jujuba seeds, Dimocarpus longan fruits, and Lactuca sativa leaves, using animal models. Behavioral analyses, including an analysis of the total sleep time of Drosophila melanogaster, were conducted to select the optimal mixed ratio of the three botanical extracts. The effects were verified in a caffeine-induced sleepless model, specific neurotransmitter receptor antagonists, and ICR mice. In D. melanogaster exposed to 2.0% of each extract, group behavior was significantly reduced, and the mixed extracts of Z. jujuba, D. longan, and L. sativa (4:1:1 and 1:4:1) significantly increased the total sleep time with individual fruit flies. In the caffeine-induced insomnia model, mixed extracts (4:1:1 and 1:4:1) led to the highest increase in total sleep time. An analysis of locomotor ability revealed a significant reduction in the mobility percentage in the mixed extract groups (0:0:1, 1:0:1, 1:1:1, 4:1:1, and 1:4:1). The administration of Z. jujuba extract and mixed extracts (4:1:1) significantly increased the expression of GABAA-R, whereas the administration of the mixed extracts (4:1:1) and (1:4:1) significantly increased the expression of GABAB-R1 and GABAB-R2, respectively. D. longan extract and the mixed ratio (1:4:1) reduced the subjective nighttime movement and increased the total sleep time in the presence of flumazenil. An analysis of ICR mice indicated that the administration of mixed extracts (4:1:1) significantly increased sleep duration in a dose-dependent manner. These results indicated that the mixed ratio of Z. jujuba, D. longan, and L. sativa extracts, particularly the mixed ratio of 4:1:1, may have sleep-enhancing effects in fruit flies and mice. The study also identified changes in gene expression related to GABA receptors, indicating the potential mechanism for the observed sleep-promoting effects.

Dendropanax morbiferus is highly valued in traditional medicine and has been used to alleviate the symptoms of numerous diseases owing to its excellent antioxidant activity. This study aimed to evaluate the sleep promotion and related signaling pathways of D. morbiferus extract (DE) via behavioral analysis, molecular biological techniques, and electrophysiological measurements in invertebrate and vertebrate models. In Drosophila, the group treated with 4% DE experienced decreased subjective nighttime movement and sleep bout and increased total sleeping time. Moreover, substantial changes in locomotor activity, including distance moved, velocity, and movement, were confirmed in the 4% DE-treated group. Compared to Drosophila in which insomnia and oxidative stress were induced by exposure to 0.1% caffeine, the DE-treated group improved sleep-related parameters to the level of the normal group. In the Drosophila model, exposure to 4% DE upregulated the expression of gamma-aminobutyric acid (GABA)-related receptors and serotonin receptor (5-HT1A), along with the expression of antioxidant-related factors, glutathione, and catalase. In the pentobarbital-induced sleep test using ICR mice, the duration of sleep was markedly increased by high concentration of DE. In addition, through the electroencephalography analysis of SD-rats, a significant increase in non-rapid-eye-movement sleep and delta waves was confirmed with high concentrations of DE administration. The increase in sleep time and improvement in sleep quality were confirmed to be related to the expression of altered GABA receptors and the enhancement of the contents of the neurotransmitters GABA and serotonin (5-HT) because of high DE administration. High-dose administration of DE also increased the expression of antioxidant-related factors in the brain and significantly decreased malondialdehyde content. Taken together, DE induced improvements in sleep quantity and quality by regulating neurotransmitter content and related receptor expression, along with high antioxidant activity, and may have a therapeutic effect on sleep disorders.

Abstract In multiple myeloma (MM), a high number of focal lesions (FL) detected using positron emission tomography/computed tomography (PET/CT) was found to be associated with adverse prognosis. To design a new risk stratification system that combines the Revised International Staging System (R-ISS) with FL, we analyzed the data of 380 patients with newly diagnosed MM (NDMM) who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis. The K-adaptive partitioning algorithm was adopted to define subgroups with homogeneous survival. The combined R-ISS with PET/CT classified NDMM patients into four groups: R-ISS/PET stage I (n = 31; R-ISS I with FL ≤ 3), stage II (n = 156; R-ISS I with FL > 3 and R-ISS II with FL ≤ 3), stage III (n = 162; R-ISS II with FL > 3 and R-ISS III with FL ≤ 3), and stage IV (n = 31; R-ISS III with FL > 3). The 2-year overall survival rates for stages I, II, III, and IV were 96.7%, 89.8%, 74.7%, and 50.3%. The 2-year progression-free survival rates were 84.1%, 64.7%, 40.8%, and 17.1%, respectively. The new R-ISS/PET was successfully validated in an external cohort. This new system had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.

Introduction: False-positive inconclusive polymerase chain reaction (PCR) results against severe acute respiratory syndrome coronavirus 2 were not low and have potentially harmful effects. We aimed to find parameters to differentiate positive cases from false-positive ones, and suggest an optimal scheme and follow-up period for inconclusive results. Methods: Cases with inconclusive PCR tests among healthcare personnel from February 2020 to June 2021 were classified as confirmed positive, clinically positive, and clinically negative groups, which were compared. The diagnostic accuracy of follow-up tests and composites of clinical and laboratory data were analyzed. Results: Symptoms, contact history, and lower cycle threshold of the N gene were more common in the COVID-19 positive group. The scoring schemes combining symptom and contact history with follow-up PCR results had higher sensitivities than the PCR tests only modality. Follow-up tests up to 5 days combined with symptoms and contact history could discriminate between positive and negative cases. Conclusion: A follow-up PCR test up to day 5 with clinical features might predict positivity and shorten the quarantine period in most healthcare personnel.

BackgroundCastleman disease (CD), classified as unicentric CD (UCD) or multicentric CD (MCD), is a rare non-neoplastic lymphoproliferative disorder of unknown origin. Owing to its rarity, the clinical characteristics, therapeutic modalities, treatment outcomes, and prognostic factors related to UCD or MCD are not well defined.MethodWe retrospectively analyzed 88 patients with CD, including those with hyaline-vascular, plasma-cell, mixed type, hypervascular, and plasmablastic subtypes, for presenting symptoms, physical, laboratory, and radiologic findings, and treatment response in the Korean population.ResultsThe median patient age was 44 years (range: 18–84 years) with slight predominance of women (53.4%). UCD and MCD accounted for 38.6% (n=34) and 61.4% (n=54) of cases, respectively. Histopathologically, UCD patients were classified as 88.2% (n=30) hyaline-vascular and 11.8% (n=4) plasma cell types, whereas MCD patients were classified as 27.8% (n=15) hypervascular, 61.1% (n=33) plasma cell, 7.4% (n=4) mixed, and 3.7% (n=2) plasmablastic types. Twelve (13.6%) patients exhibited a poor performance status with an Eastern Cooperative Oncology Group score of 2. The most common presenting symptom was sustained fever, followed by fatigue, anorexia, peripheral edema, and weight loss. Furthermore, splenomegaly, pleural effusion, and ascites were observed to be associated with CD. Surgical resection and siltuximab were the preferred treatment modalities for UCD and MCD, respectively, with favorable symptomatic, laboratory, and radiologic outcomes and safety profiles. The overall survival was 90.2%, with no significant difference between the UCD and MCD groups (p=0.073), but progression-free survival was significantly poorer in the MCD group (p=0.001). Age ≥60 years and splenomegaly significantly affected the overall and progression-free survival rates.ConclusionPatients with UCD had favorable outcomes with surgical resection of a solitary mass, whereas in patients with MCD, old age and splenomegaly were identified as independent prognostic factors. Further well-designed prospective studies under advancing knowledge of the pathophysiology of MCD are warranted to establish suitable guidelines for the discontinuation or prolonging infusion intervals of siltuximab and treatment modalities for HHV-8 positive MCD patients or patients with siltuximab failure.

Background/Aims Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. Methods In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. Results On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. Conclusions Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.

Abstract Background TR4, an orphan nuclear receptor plays a key role in glucose and lipid metabolism by regulating the expression of genes involved in energy metabolism. We previously reported that overexpression of TR4 in 3T3-L1 adipocytes promotes lipid accumulation in part by facilitating fatty acid uptake and synthesis, indicating that TR4 tightly regulates lipid homeostasis during adipogenesis. Here, we report that β-catenin suppresses TR4 transcriptional activity and that this inhibition is achieved through induction of Slug gene, a well-known transcription repressor in a variety of cells Methods To generate the stable cell line, 3T3-L1 cells were transfected with plasmids then cultured in presence of geneticin and/or blasticidin for 2 weeks. The lipid accumulation was measured by Oil Red O. The TR4-Slug and TR4-β-catenin interactions were checked by GST pull-down and mammalian two-hybrid assay. The TR4 transcriptional activities on various promoters were measured by luciferase activity. To check the binding affinity of TR4, we performed the gel shift and chromatin immunoprecipitation (ChIP) assay. Gene expression was detected by RT-qPCR at the mRNA level and western blotting at the protein level. Results Stable overexpression of Slug gene in 3T3-L1 preadipocytes strongly inhibited differentiation of 3T3-L1 preadipocytes. Using GST pull-down, gel shift and ChIP assays, we found that Slug abolished the formation of TR4 homodimers through direct interaction with TR4 and reduced the binding affinity of TR4 for its response elements located in TR4 target gene promoters such as fatty acid transport protein 1 and pyruvate carboxylase. Consistently, Slug inhibited TR4 target gene expression and was accompanied by repression of TR4-induced lipid accumulation in 3T3-L1 adipocytes. Conclusions Our results demonstrated that Slug inhibits 3T3-L1 adipogenesis through suppression of TR4 transcriptional activity.

Duplex nanoporous Cu was successfully fabricated by dealloying a dual-phase Mg–Cu precursor alloy consisting of intermetallic Mg2Cu and MgCu2. The duplex nanoporous Cu with embedded nanoporous struts exhibited highly enhanced strength compared to the typical monolithic nanoporous Cu under both compressive and flexural test conditions at room temperature; the duplex np-Cu sample exhibited a 12 times higher compressive strength and a 40 times greater flexural strength than the monolithic np-Cu sample. Factors responsible for the strength enhancement in the duplex nanoporous Cu are discussed.

We report that the corrosion resistance of a Mg–Sn-based alloy with Mg2Sn precipitates can be considerably improved by surface modification using pulsed electron beam treatment. The alloy subjected to a pulse electron beam treatment showed a modified surface layer with a thickness of ∼12 µm, appearing more resistant to corrosion attack than the bare surface of the alloy. In 0.6 M NaCl solution, the alloys with and without the surface modification exhibited average corrosion rates of 4.3 and 8.1 mm y −1, respectively. The improved corrosion resistance was attributed to reduced cathodic activation, resulting from the surficial reduction of relatively noble Mg2Sn precipitates.

Background: Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML. Methods: We compared AML patients who received IC ( n = 89) to those who received a VEN in combination with hypomethylating agents or low dose cytarabine (VEN combination) ( n = 54) as their first- or second-line salvage after failing anthracycline-containing intensive chemotherapy. Results: The median age was 49 years, and significantly more patients in the VEN combination group were in their second salvage and had received prior stem cell transplantation (SCT). Overall response rates including CR, CRi, and MLFS were comparable (44.0% for IC vs. 59.3% for VEN combination, p = 0.081), but VEN combination group compared to IC group tended to show lower treatment related mortality. The rate of bridging to SCT was the same (68.5%), but the percentage of SCT at blast clearance was significantly higher in the VEN-combined group (62.3% vs. 86.5%, p = 0.010). After median follow-up periods of 22.5 (IC) and 11.3 months (VEN combination), the median overall survival was 8.9 (95% CI, 5.4-12.4) and 12.4 months (95% CI, 9.5-15.2) ( p = 0.724), respectively. Conclusion: VEN combination provides a comparable anti-leukemic response and survival to salvage IC, and provide a bridge to SCT with better disease control in medically-fit patients with R/R AML.

Background: Cord blood transplantation (CBT) has been reported as an acceptable option with comparable outcomes to conventional donors in adults with acute lymphoblastic leukemia (ALL). We aimed to analyze the long-term CBT outcomes and risk factors for early and long-term mortalities. Methods: Between 2006 and 2020, 112 patients (median age: 35 years; 62 Ph-negative ALL and 50 Ph-positive ALL) were treated with double CBT. Conditioning regimen consisted of total body irradiation (12 Gy) plus cytarabine (9.0 g/m 2 ) plus fludarabine (150 mg/ m 2 ), and graft-versus-host disease (GVHD) prophylaxis was attempted by administering tacrolimus plus mycophenolate mofetil. Results: The median time for neutrophil and platelet recovery was 25 days (range: 5–59 days) and 34 days (range: 7–185 days), respectively. The cumulative incidence of acute GVHD at 1 year was 43.8%, and the incidence of acute GVHD with grades III–IV was 8.9%. The overall cumulative incidence of chronic GVHD was 22.0%, and the incidence of moderate to severe chronic GVHD was 8.5%. After a median follow-up of 60.1 months (range: 5.7–181.3 months), the 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) were 15.9% and 28.5% (9.7% and 27.2% for CR1), respectively, and the 5-year overall survival (OS) was 57.9% (66.5% for CR1). In multivariate analysis of 88 patients receiving double CBT in CR1, delayed CR1 was related to high CIR, and age older than 40 years was associated with high NRM and early mortality. Unexpectedly, Ph-positive ALL with MRD had a higher NRM and early mortality than Ph-negative ALL and Ph-positive ALL without MRD subgroups, possibly due to delayed neutrophil and platelet recovery. Conclusion: Our data suggest that double CBT for adult ALL in CR1 has a greater benefit in younger patients and in patients with Ph-positive ALL without MRD or Ph-negative ALL.

PurposeThe significance of Epstein-Barr virus (EBV) infections for the prognosis of patients with peripheral T-cell lymphomas (PTCLs), specifically angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS), remains unclear. The Epstein-Barr encoding region can be used to detect EBV in tissue sections by in situ hybridization (ISH) and by polymerase chain reaction (PCR) assays of peripheral blood samples from patients with PTCLs. This study compared the outcomes patients with AITL or PTCL-NOS for whom the presence of EBV infection was assessed by these two methods.Patients and MethodsThis was a retrospective study of patients newly diagnosed with AITL or PTCL-NOS. All patients were selected from a single transplantation center. EBV-positive lymphomas were detected at the time of diagnosis in tissue sections by ISH or in the blood by PCR.ResultsOut of a cohort of 140 patients with histologically confirmed AITL or PTCL-NOS, 105 were EBV-positive. The 3-year overall survival of patients with EBV-positive TCL was 43.3% compared to 68.6% in patients with EBV-negative TCL (p = .01). Patients who were treated with autologous or allogeneic hematopoietic stem cell transplantation (n = 28 and n = 11, respectively) or chemotherapy alone (n = 66) had 3-year survival rates of 67.0%, 62.3%, and 30.2%, respectively (p

Inotuzumab ozogamicin (INO) showed improved treatment outcomes for relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) but can induce hepatotoxic adverse events. Hepatic venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) frequently develops after allogeneic hematopoietic cell transplantation (allo-HCT), and INO is a strong pretransplant risk factor. However, VOD/SOS can occur just after INO therapy. Here, we describe a BCP-ALL patient treated with INO for isolated extramedullary relapse after allo-HCT. The patient experienced elevated liver enzymes with ascites at 21 days from the last INO dose. Although she met the criteria for VOD/SOS, the diagnosis was challenging because of her ongoing hepatic graft- versus -host disease (GVHD) and normal portal vein flow on Doppler sonogram. The radiologist suggested liver cirrhosis based on computed tomography, with VOD/SOS, liver cirrhosis, and GVHD assumed to be differential diagnoses. She received supportive care with GVHD management; however, due to progressive hepatic failure, we conducted emergent deceased-donor liver transplantation, and the pathologic findings indicated VOD/SOS. Her leukemia was stable, but she died of sepsis after 3 months. INO use is a high-risk factor for VOD/SOS, but an accurate diagnosis can be challenging due to various hepatic complications. Early diagnosis and proper management for VOD/SOS is important for improved outcomes.

Abstract In adult patients with relapsed or refractory (R/R) Philadelphia chromosome‐negative (Ph‐negative) B‐cell presursor acute lymphoblastic leukemia (BCP‐ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph‐negative BCP‐ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo‐HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1

Abstract Ibrutinib is highly effective in patients with relapsed or refractory mantle cell lymphoma (MCL) in major clinical trials. Although there has been a dramatic improvement in survival outcomes in the salvage setting, nonresponders to ibrutinib have a bleak prognosis. Therefore, this retrospective study was conducted to identify the most appropriate therapeutic strategy and prognosis‐related factors to predict the response of patients with relapsed or refractory MCL to ibrutinib monotherapy. Thirty‐three consecutive refractory or relapsed MCL patients treated with ibrutinib were analyzed in this study. The median overall survival (OS) and progression‐free survival (PFS) after initiation of ibrutinib were 35.1 months and 27.4 months, respectively. Risk factor analysis showed that high risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI) and nonresponse to ibrutinib at the first three cycles were significantly associated with inferior OS. Poor PFS was associated with high‐risk biologic MIPI, prior bendamustine exposure, and nonresponse to ibrutinib during the first three cycles. After ibrutinib failure, primary nonresponders had poorer OS and PFS than inconsistent responders. The overall response rate for the first salvage therapy was only 33%, with a median TTP of 3.2 months. There was no effective therapeutic strategy except for allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Although ibrutinib responders exhibited favorable survival outcomes, nonresponders had a dismal prognosis. To overcome these limitations, it may be necessary to modify therapeutic strategies, such as selecting inconsistent responders for earlier allo‐HSCT.

Premature drug release and poor controllability is a challenge in the practical application of tumor therapy, which may lead to poor chemotherapy efficacy and severe adverse effects. In this study, a reactive oxygen species (ROS)-cleavable nanoparticle system (MXene-TK-DOX@PDA) was designed for effective chemotherapy drug delivery and antibacterial applications. Doxorubicin (DOX) was conjugated to the surface of (3-aminopropyl)triethoxysilane (APTES)-functionalized MXene via an ROS-cleavable diacetoxyl thioketal (TK) linkage. Subsequently, the surfaces of the MXene nanosheets were coated with pH-responsive polydopamine (PDA) as a gatekeeper. PDA endowed the MXene-TK-DOX@PDA nanoparticles with superior biocompatibility and stability. The MXene-TK-DOX@PDA nanoparticles had an ultrathin planar structure and a small lateral size of approximately 180 nm. The as-synthesized nanoparticles demonstrated outstanding photothermal conversion efficiency, superior photothermal stability, and a remarkable extinction coefficient (23.3 L g−1 cm−1 at 808 nm). DOX exhibited both efficient ROS-responsive and pH-responsive release performance from MXene-TK-DOX@PDA nanoparticles due to the cleavage of the thioketal linker. In addition, MXene-TK-DOX@PDA nanoparticles displayed high antibacterial activity against both Gram-negative Escherichia coli (E. coli) and Gram-positive Bacillus subtilis (B. subtilis) within 5 h. Taken together, we hope that MXene-TK-DOX@PDA nanoparticles will enrich the drug delivery system and significantly expand their applications in the biomedical field

Introduction: Donor lymphocyte infusion (DLI) is one of the effective options for post-transplant disease control of myelodysplastic syndrome (MDS). Its success or failure depends on the induction of antitumor immune reactions, durability of clinical responses, and severity of unwanted toxicities mainly from graft- versus -host disease (GVHD). Methods: By analyzing 61 patients receiving DLI for post-transplant MDS relapse, we assessed treatment outcomes and affecting factors, especially focusing on the level of relapse (hematological, molecular, and imminent relapse). Results: The response rate (42.1%, 36.4%, 72.7%), and overall survival (OS) at 2 years (27.8%, 45.5%, 70.1%) were different for each relapse level with imminent relapse group showing the most promising results. For OS, response to DLI or pre-DLI chemotherapy, and time to relapse were independent prognostic factors. Meanwhile, post-DLI GVHD and time to relapse were independently predictive for DLI response; post-DLI GVHD was predictive for DLI response, but not for OS, suggesting a potential detrimental impact of GVHD on survival. The incidence of GVHD and GVHD-related deaths were 37.7% and 10.0%, respectively, and CD3 + cell doses triggering GVHD tended to be lower in cases with haploidentical donor or imminent relapse. Conclusion: Despite being limited by small number of cases and its retrospective nature, this study again demonstrated the therapeutic effects of DLI in relapsed MDS, and that earlier detection and intervention at lower level relapse might possibly be associated with better results. Furthermore, we propose that tailored cell dosing schedule based on relapse level and donor source may be helpful in minimizing fatal GVHD.

Background: Hemophagocytic lymphohistiocytosis (HLH) can be life-threatening if not detected and treated appropriately. The diagnosis of HLH can be confusing due to other similar febrile diseases that present with cytopenia. Natural-killer cell (NK)-cytotoxicity is an important diagnostic parameter for primary HLH; however, its role in secondary HLH in adults has not been well-elucidated. Methods: We prospectively enrolled 123 adult patients with febrile conditions accompanied by cytopenia or marrow hemophagocytosis. A diagnosis of HLH was based on HLH-2004 criteria and treated based on HLH-94 protocol. NK-cytotoxicity was calculated at the time of diagnosis by K562-cell direct lysis using flow-cytometry. Results: HLH ( n = 60) was determined to be caused by Epstein–Barr virus (EBV) ( n = 11), infection other than EBV ( n = 16), malignancies ( n = 19), and unknown ( n = 14). Febrile diseases other than HLH ( n = 63) were diagnosed as autoimmune disease ( n = 22), malignancies ( n = 21), infection ( n = 12), non-malignant hematological diseases ( n = 6), and unknown ( n = 2). A lower NK-cytotoxicity level was observed at diagnosis in patients with HLH, compared with other causes of febrile disease (12.1% versus 26.2%, p

Three different types of typical Korean foods were studied to investigate the effect of monosodium glutamate (MSG) on the sensory characteristics and hedonic perception of sodium- or sugar-reduced samples. The first consumer test (n = 300) was conducted to evaluate the overall liking (OL) of the samples containing four different levels of salt and sugar contents without added MSG, while the second consumer test (n = 300) was designed to examine the effects of MSG on the samples containing reduced salt and sugar contents with the lowest observed OL in the first consumer test. The results showed that the intensity of the umami taste and saltiness of the samples increased, whereas sourness and bitterness were suppressed with added MSG. The samples with the lowest salt contents were observed to be acceptable to consumers after MSG addition, indicating a 23% reduction in sodium intake. Bitterness was partially masked, while sweetness, umami taste, and saltiness were the main factors affecting the OL after MSG addition. However, no consistent results of added MSG on the sensory attributes of samples with reduced sugar contents were observed, possibly indicating that the effect of umami taste on sweetness depends on the MSG concentration used or the type of food studied. This study could be beneficial to researchers who want to know the optimal level of MSG required to reduce the sodium or sugar contents in cooked food.

Background: Preconditioning intensity, donor choice and graft- versus -host disease (GVHD) prophylaxis of allogeneic hematopoietic cell transplantation (allo-HCT) for advanced myelofibrosis (MF) have not been fully elucidated. Methods: Thirty-five patients with advanced MF were treated with reduced-intensity conditioning (RIC) allo-HCT. We searched for matched sibling donors first, followed by matched or mismatched unrelated donors and familial mismatched donors. Preconditioning regimen consisted of fludarabine (total 150 mg/m 2 ) and busulfan (total 6.4 mg/kg) with total body irradiation ⩽400cGy. Results: All showed engraftments, but four showed either leukemic relapse or delayed graft failure. Two-year overall survival (OS) and non-relapse mortality (NRM) was 60.0% and 29.9%, respectively. Acute GVHD was observed in 19 patients, and grade III–IV acute GVHD (eight grade III and four grade IV) was higher in human leukocyte antigen (HLA)-mismatched donor HCT compared with HLA-matched HCT (70% versus 20%). Chronic GVHD was observed in 16 patients, and a cumulative incidence of severe chronic GVHD was 33% in HLA-mismatched donor HCT and 7.7% in HLA-matched HCT. Significant hepatic GVHD was observed in nine patients (five acute, four chronic) and six of them died. Multivariate analysis revealed inferior OS in HLA-mismatched donor HCT (hazard ratio (HR) = 6.40, 95% confidence interval (CI) 1.6–25.7, p = 0.009) and in patients with high ferritin level at the time of pre-conditioning period (HR = 7.22, 95% CI 1.9–27.5, p = 0.004), which were related to higher incidence of hepatic GVHD with high NRM rate. Conclusion: RIC allo-HCT can be a valid choice providing graft- versus -fibrosis effect for advanced MF patients. However, HLA-mismatched donor and high pre-HCT ferritin level related to fatal hepatic GVHD should be regarded as poor-risk parameters.