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Although concrete materials generally exhibit outstanding mechanical properties, it is susceptible against crack formation. It has been reported that narrow cracks (≤ 150 µm) could be naturally sealed in the cement matrix by externally supplied water-induced hydration. However, the crack width of larger than 150 µm is difficult to be sealed without using additional self-healing admixture. In this study, the self-healing cementitious mortar was successfully developed by using a combination of polyvinyl alcohol (PVA) fiber and superabsorbent polymer (SAP), aiming to heal the wide cracks. Although the mechanical properties were slightly reduced, it shows outstanding self-healing performance by using the dual admixtures. A self-healing rate of 60% was observed in the control sample with an initial crack width of 300 µm, while a self-healing rate of nearly 100% was confirmed with suitable SAP and PVA. In addition, it was confirmed that lower hydration degree of self-healing mortar in early stage contributes to the enhanced self-healing performance of developed composite system by internally supplied water from SAP. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function. Methods and results: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation. Conclusion: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma. [ABSTRACT FROM AUTHOR]

Electrical resistance measurement is central to materials characterization, circuit analysis and resistance-based sensing. Resistance measurement involving the two-probe method (involving two electrical connections) is known to overassess the resistance, due to the electrode-specimen contact resistance. Resistance measurement involving the four-probe method (involving four electrical connections) is advantageous in that it essentially excludes the contact resistance at the connection-specimen interface. Nevertheless, the two-probe method is widely used, because of the simplicity of having only two connections. In the two-probe method, the current passes through the specimen and connections. The connection-related stray inductance is found in this work to cause large additional overassessment of the two-probe resistance when the electrical connection configuration entails current direction changes. The connections pertain to electrical leads and clips. The inductance increase due to a current direction change is in line with Faraday's law. Mere constriction or spreading of the current due to the connections also increases the inductance, but it does not influence the two-probe resistance. The inductance and two-probe resistance increase with the lead length because of the connection-related inductance, not because of the negligible increase in the lead resistance. An inductance increase of ≤ 80% causes a two-probe resistance increase of ≤ 278%. The specimen in this work is aluminum. It does not need to be magnetic. The connections in this work are also not magnetic. This inductance-related source of two-probe resistance overassessment is reported here for the first time. [ABSTRACT FROM AUTHOR]

As global temperatures have steadily increased over past decades, studying of the impacts of heat stress on morpho-physiological traits and economic yields of horticultural crops have been increasingly gained attentions by many scientists and farmers. Hot pepper (Capsicum annuum L.) is an important vegetable crop mostly grown in open-fields in South Korea. In this study, the impacts of prolonged heat stress on three hot pepper genotypes differing by levels of stress susceptibility were evaluated. The study was conducted in two different temperature-controlled greenhouses for 75 days. 48 days old plants were grown in control and heat-treated greenhouses where the temperatures had been set at 30 °C and 35 °C during the day for 75 days, respectively. Morphological, physiological, and nutrient characteristics of three accessions were measured. All hot pepper accessions were enabled to recover from prolonged heat stress exposures within approximately a month. The phenomenon of recovery was observed in some significant morphological and physiological characteristics. For example, the plant growth rate and photosynthesis rate significantly increased after 40th days of heat treatment. The heat stress sensitivity varied between genotypes. The plants that produced more fruits over biomass at early stage of heat treatment had relatively slow recovery, resulting in the largest yield loss. This key morphological characteristic can be used for future breeding program to adapt the prolonged heat stress. [ABSTRACT FROM AUTHOR]

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing symptoms in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Brain imaging data were acquired from 71 healthy participants. WM regions of mirroring network were analyzed using tract-based spatial statistics. After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. We found that self-compassion scale total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores were also negatively correlated with FA values of the same regions. These FA values were negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Our findings suggest levels of SC may be associated with WM microstructural changes of SLF in healthy individuals. These lower WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies. [ABSTRACT FROM AUTHOR]

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection. [ABSTRACT FROM AUTHOR]

The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P < 0.001, and 21.5 vs. 60.9 months, P < 0.001, respectively). Primary PCL diagnosed using the revised criteria presented with higher total calcium levels and serum creatinine levels, lower platelet counts and frequent organomegaly and plasmacytoma at diagnosis. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum β2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs ≥ 5% in a peripheral blood smear is appropriate for PCL diagnosis. [ABSTRACT FROM AUTHOR]

This paper reports a new nondestructive noncontact method of sensing surface roughness, particularly the surface undulation produced in the plowing stage of wear. This method involves inductance measurement. It is fast, provides global information and is suitable for real-time monitoring, but it is limited to electrical conductors. This amounts to structural self-sensing. Ultramild abrasive wear primarily in the plowing regime, with areal weight loss ≤ 0.075 g/cm2 and ≤ 0.040 g/cm2 for steel and aluminum, respectively (i.e., thickness loss ≤ 0.30 mm and ≤ 0.48 mm for steel and aluminum, respectively), is effectively sensed by this method. The inductance measurement involves two electrical contacts (clips) and an LCR meter (2 kHz). The inductance increases monotonically with increasing degree of wear primarily in the plowing regime, beyond which it does not increase further. This is due to the sensitivity of the inductance to the surface undulation, as expected from Faraday’s law. Longitudinal wear (wear performed in the inductance measurement direction, i.e., direction along the metal bar length) and transverse wear (wear performed along the direction perpendicular to the inductance measurement direction) give similar weight loss. However, the fractional increase in inductance due to wear is greater for transverse wear than longitudinal wear, as expected from Faraday’s law. Hence, the inductance method can discern the surface undulation direction, i.e., the wear direction, but the weight loss method cannot. The fractional increase in inductance due to wear is greater for steel (magnetic) than aluminum (not magnetic). However, magnetic character is not required for the sensing. [ABSTRACT FROM AUTHOR]

Compared to ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) patients with symptoms related invasion beyond the ocular adnexa, the different approaches to staging assessment may be required in OAML patients with symptoms limited to the ocular adnexa. Seventy-six patients to be diagnosed with OAML and performed bone marrow biopsy and imaging study at Yeungnam University Hospital in 1995–2014 were enrolled. Patients with symptoms limited to the ocular adnexa were included. Computed tomography, magnetic resonance imaging, positron emission tomography (PET), and bone marrow biopsies were performed for diagnosis, NM staging and follow up evaluation. Most patients were treated with external beam irradiation (median dose, 30 Gray (Gy)). The relapse-free survival (RFS) was analyzed according to the tumor laterality and TNM stage. The median follow-up period was 72 months. The 5-year RFS and overall survival rates were 82.1% and 95.6% respectively. Of all 76 patients, lymph node and bone marrow involvement was identified in 1 patient, respectively. Among the 3 patients with T4 stage as tumor invasion beyond ocular adnexa, bone marrow involvement was confirmed in a patient with left cheek invasion. Only 11 of the 43 patients who underwent PET showed positive uptakes in orbital lesion. The patients with advanced stage were alive without recurrences. Bone marrow examination is useful in OAML patients with T4 for extended stage assessment. The AJCC TNM staging system was not significantly predictive factor for relapse, but may contribute to clarifying the patient group that needs bone marrow study. [ABSTRACT FROM AUTHOR]

Purpose: This observational study aimed to evaluate the safety and efficacy of pegteograstim prophylaxis in patients with lymphoma and solid malignancies. Methods: This study was conducted at 18 sites in Korea between November 2015 and August 2018. Results: In total, 611 patients (female, 61.2%) with a median age of 58 (range, 18–88) years were included. Most patients had lymphomas (n = 371, 60.7%) and breast cancer (n = 230, 37.6%) and were administered R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone per 21 days) (n = 284, 46.5%) and AC (doxorubicin and cyclophosphamide) (n = 177, 29.0%). The total pegteograstim dose in the 611 patients was 14,970 mg (2495 doses), with each patient receiving an average daily dose of 6.0 mg. Neutropenia grade 4 occurred in 97 patients (15.9%), and febrile neutropenia (FN) occurred in 31 patients (5.1%). Among the 611 patients, 267 patients (43.7%) developed 882 adverse events (AEs), and 11 patients (1.8%) experienced 18 adverse drug reactions (ADRs). There were 62 patients (10.2%) who experienced 81 cases of serious adverse events (SAEs), with FN and pneumonia being the most frequent at 14 and 13 episodes, respectively, in 13 patients (2.1%). Meanwhile, 1 patient (0.2%) developed 2 episodes of serious ADRs (grade 1 and grade 2 hypotension). No safety concerns in the elderly and patients with liver and/or renal disease were identified. Conclusion: The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases. [ABSTRACT FROM AUTHOR]

The present study introduces a systematic approach using analytical quality by design (AQbD) methodology for the development of a qualified liquid chromatographic analytical method, which is a challenge in herbal medicinal products due to the intrinsic complex components of botanical sources. The ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS) technique for 11 flavonoids in Genkwa Flos was utilized through the entire analytical processes, from the risk assessment study to the factor screening test, and finally in method optimization employing central composite design (CCD). In this approach, column temperature and mobile solvent slope were found to be critical method parameters (CMPs) and each of the eleven flavonoid peaks' resolution values were used as critical method attributes (CMAs) through data mining conversion formulas. An optimum chromatographic method in the design space was calculated by mathematical and response surface methodology (RSM). The established chromatographic condition is as follows: acetonitrile and 0.1% formic acid gradient elution (0–13 min, 10–45%; 13–13.5 min, 45–100%; 13.5–14 min, 100–10%; 14–15 min, 10% acetonitrile), column temperature 28℃, detection wavelength 335 nm, and flow rate 0.35 mL/min using C18 (50 × 2.1 mm, 1.7 μm) column. A validation study was also performed successfully for apigenin 7-O-glucuronide, apigenin, and genkwanin. A few important validation results were as follows: linearity over 0.999 coefficient of correlation, detection limit of 2.87–22.41, quantitation limit of 8.70–67.92, relative standard deviation of precision less than 0.22%, and accuracy between 100.13 and 102.49% for apigenin, genkwanin, and apigenin 7-O-glucuronide. In conclusion, the present design-based approach provide a systematic platform that can be effectively applied to ensure pharmaceutically qualified analytical data from complex natural products based botanical drug. [ABSTRACT FROM AUTHOR]

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival. [ABSTRACT FROM AUTHOR]

Purpose: Although several studies have examined tyrosine kinase inhibitor (TKI)-induced hepatotoxicity, the majority of patients in those studies displayed low-grade (grade I–II) hepatotoxicity. The purpose of this study was to investigate factors affecting high-grade (grade III–IV) hepatotoxicity of TKIs. Methods: This multi-center, retrospective study used individual patient data from five studies that examined factors affecting hepatotoxicity by TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib). Odds ratio (OR) and adjusted OR (AOR) were estimated from univariate and multivariate analyses, respectively. Results: Data from 1279 patients treated with TKIs were analyzed. The rate of patients who experienced high-grade hepatotoxicity after TKI administration was 5.5%. In multivariable analysis, H2 blockers and CYP3A4 inducers increased high-grade hepatotoxicity 2.2- (95% CI 1.255–3.944) and 3.3-fold (95% CI 1.260–8.698), respectively. Patients with liver metastasis revealed a 3.4-fold (95% CI 1.561–7.466) higher risk of high-grade hepatotoxicity. Among underlying malignancies, pancreatic cancer and other cancers including acute lymphoblastic leukemia increased the risk of high-grade hepatotoxicity by 2.6- and 24.3-fold, respectively, whereas breast cancer decreased the risk (AOR 0.3, 95% CI 0.106–0.852), compared to non-small cell lung cancer. In patients who administrated TKIs which form reactive metabolites, use of CYP3A4 inducers and liver metastasis increased incidence of high-grade hepatotoxicity by 3.0- and 2.3-fold, respectively. In patients with EGFR mutation, exon 19 deletion and use of proton pump inhibitors were risk factors for high-grade hepatotoxicity in addition to liver metastasis and use of H2 blockers. Conclusion: The use of H2 blockers, presence of liver metastasis, and CYP3A4 inducers were associated with high-grade hepatotoxicity of TKIs. In subgroup analyses, presence of exon 19 deletion, and/or proton pump inhibitors, was additional risk factors for high-grade hepatotoxicity in special patients and use of specific TKIs. Close liver function monitoring is recommended, especially in patients with liver metastasis or using H2 blockers or CYP3A4 inducers. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) positivity in diffuse large B cell lymphoma (DLBCL) provokes a critical oncogenic mechanism to activate intracellular signaling by LMP1. LMP1 specifically mimics the role of BTK-dependent B cell receptor. Therefore, a trial considering RCHOP therapy along with ibrutinib (I-RCHOP) in combination was conducted among patients with EBV-positive DLBCL. This study was an open-label, single-arm, prospective multicenter phase II clinical trial. Patients received 560 mg of ibrutinib with RCHOP every 3 weeks until 6 cycles were completed or progression or unacceptable toxicity was observed. The primary endpoint was objective response, while secondary endpoints included toxicity, progression-free survival, and overall survival. A matched case-control analysis was completed to compare the efficacy and toxicity of I-RCHOP and RCHOP, respectively, in EBV-positive DLBCL patients. From September 2016 to August 2019, 24 patients proven to have EBV-positive DLBCL in the tissue were enrolled and received I-RCHOP. Their median age was 58 years (range, 28-84 years). The objective overall response was 66.7%, including 16 patients who achieved complete response after 6 cycles. Patients aged younger than 65 years presented a superior OR (87.5%) as compared with those older than 65 years (25.0%; p = 0.01). In a matched case-control study, I-RCHOP therapy provoked a more favorable complete response rate (87.3%) than did RCHOP (68.8%) in those younger than 65 years. Treatment-related mortality was linked most frequently with I-RCHOP therapy (four patients presented with unusual infection without Gr3/4 neutropenia) in the older age group (age ≥ 65 years). In conclusion, in this phase II trial for EBV-positive DLBCL, I-RCHOP was effective but did not show a significant improvement in response and survival in comparison with RCHOP. Also, I-RCHOP promoted serious toxicity and treatment-related death in older patients. [ABSTRACT FROM AUTHOR]

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes. [ABSTRACT FROM AUTHOR]

The synthesis of (porphyrinato)Sn-viologen, 1, and its supramolecular complexation with cucurbit[7]uril (CB[7]) were studied. 1H NMR spectroscopic studies obviously reveal that 1 forms a 1 : 2 supramolecular complex with CB[7] through the inclusion of viologen moieties of 1 into the cavity of CB[7]. The cyclic voltammetric study supports that the binding affinity of the radical cation forms is comparable to that of the di-cation viologen toward CB[7]. The fluorescence arising from the porphyrin moiety is significantly quenched upon the complexation of 1 with CB[7]. The ps-time-resolved fluorescence and ns-transient absorption spectroscopic studies reveal that the photoinduced electron transfer (PET) between viologen and Sn(iv) porphyrin of 1 takes place from the first excited singlet (S1) state and the second excited triplet (T2) state of the porphyrin moiety upon complexation with CB[7], while the PET from the S1 state is negligible in the absence of CB[7]. [ABSTRACT FROM AUTHOR]

In this study we prepared tissue-adhesive hemostatic glue and assessed hemostatic effects on hepatic bleeding animal model. Alginate was used as primary polymer for the fabrication of hemostatic glue, oxidized for the introduction of the tissue-adhesive Schiff base forming aldehyde and then encoded with mussel-inspired dopa. In addition, polyallylamine (PAA) was selected for as an intra-structuring polymer which ensures the gel strength and allows instantaneous glue formation on the bleeding spot. Primary glue (OA glue) was quickly formed within 5 to 10 seconds after the mixing oxidized alginate (OA) with PAA. The degree of oxidation and the mixing ratio of OA and PAA were precisely determined based on glue formation time and gel strength. And the extend of dopa conjugation on OA was determined by the tissue adhesion force and the elasticity of the glue (Dopa-OA glue). Especially, elasticity of Dopa-OA glue was significantly enhanced after introduction of dopa to OA. Functional assay of Dopa-OA glue on hepatic bleeding animal model showed much enhanced hemostatic action. Dopa-OA glue is expected to provide novel injectable tissue adhesives for the treatment of hemorrhage caused by clinical procedures or trauma. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs.Methods: We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients.Results: Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort.Conclusion: The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs. [ABSTRACT FROM AUTHOR]

Among the several components in Korean red ginseng, the saponin components are known to have various pharmacologic activities. The objective of this study was to evaluate therapeutic effects of saponin extracts from Korean red ginseng on endometriosis and to identify microRNAs (miRNAs) associated with saponin treatment. This is an in vitro study which used human endometrial stromal cells (HESCs) obtained from patients who underwent laparoscopic surgery for endometriosis and other benign conditions. Human endometrial stromal cells were treated with saponin extracts, and microarray profiling was performed. Human endometrial stromal cells were then transfected with miRNAs identified in the profiling. After the saponin extract treatment, the expression of caspase 3 was significantly increased in HESCs. Microarray profiling revealed several miRNAs that were differentially expressed, and miR-21-5p was further validated. Expression of miR-21-5p was significantly upregulated in the endometrium of patients with endometriosis, compared with controls. Transfection of a miR-21-5p inhibitor significantly increased caspase 3 expression in HESCs. The apoptotic potential of saponin extracts and the miR-21-5p inhibitor were further validated in HESCs using flow cytometry analysis. In conclusions, treatment with saponin extracts significantly decreased the expression of miR-21-5p in HESCs from patients with endometriosis. Inhibition of miR-21-5p effectively increased the apoptotic potential of HESCs. These findings suggest that saponin extract treatment may have therapeutic potential for endometriosis via modulation of specific miRNAs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence. Study Design: The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis. Results: Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosis were 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P < .0001 and 0.50 vs 4.26 U/mL, P < .0001, respectively). Of the 28 patients, 13 (46.4%) simultaneously had adenomyosis, and 2 (7.1%) underwent LNG-IUS removal because of unresolved vaginal bleeding and dysmenorrhea. Recurrence was noted in 2 (7.1%) women. Conclusion: Postoperative LNG-IUS insertion after GnRH-a treatment is an effective approach for preventing endometriotic cyst recurrence, especially in women who do not desire to conceive. [ABSTRACT FROM AUTHOR]

Regarding the size increase, we consider that the lesion was initially an ML and then evolved into EMH due to altered hematopoiesis and mesenchymal stem cell function. Extramedullary hematopoiesis (EMH) is the proliferation of all three cell lineages in extramedullary sites occurring as a physiological compensatory phenomenon in response to altered hematopoiesis due to inadequate bone marrow function, such as anemia and myelodysplastic syndrome [[3]]. [Extracted from the article]

Background: Post-laparoscopic shoulder pain (PLSP) frequently follows a laparoscopic cholecystectomy. A proposed mechanism for PLSP is the irritation or injury of the phrenic nerve by the CO2 pneumoperitoneum during laparoscopic surgery. Here, we investigated whether a phrenic nerve block (PNB), performed under ultrasound guidance, could reduce the incidence and severity of PLSP after laparoscopic cholecystectomy.Method: Sixty patients were randomized into two groups, with one group receiving PNB with 4 ml (30 mg) of 0.75% ropivacaine (group P, n = 28) and a control group (group C, n = 32). The existence and severity of PLSP were assessed for 2 days postoperatively. A pulmonary function test (PFT) and diaphragmatic excursion test were performed pre- and postoperatively.Results: With ultrasound guidance, all PNBs were performed successfully in group P. In group P, the overall incidence and severity of PLSP decreased significantly. There were no significant differences in incisional pain, visceral pain, and analgesic requirements between the groups. Right-side diaphragmatic excursion decreased significantly in group P at 1 h postoperatively. The PFT results and respiratory discomfort assessed by a modified Borg's scale were not different significantly between the groups.Conclusion: Based on these findings, ultrasound-guided PNB can prevent or reduce the PLSP without clinically significant respiratory discomfort. [ABSTRACT FROM AUTHOR]

Megestrol acetate (MGA) belongs to the BCS class II drugs with low solubility and high permeability, and its oral absorption in conventional dosage form MGA microcrystal suspension (MGA MS) is very limited and greatly affected by food. In this study, MGA nanoemulsion (MGA NE) was formulated based on solubility, phase-diagram and release studies. Then oral bioavailability of MGA NE and MGA MS was evaluated. A randomized two-way crossover trial was conducted on six male dogs under fed and fasting conditions. Blood concentrations of MGA were analyzed using LC-MS/MS. MGA NE yielded 5.00-fold higher oral bioavailability in fasting conditions and displayed more stable absorption profiles after food intake compared with MGA MS. [ABSTRACT FROM AUTHOR]

Self-expanding non-vascular metal stents (SEMS) is now a choice of treatment for tumor-induced obstructive symptoms of gastrointestinal tract. But in-growing tumor causes re-stenosis. Here, we studied a paclitaxel-eluting nanofiber-covered stent for palliative chemotherapy of gastrointestinal cancer and its related stenosis. In vivo and in vitro feasibility of nanofiber-covered nonvascular stent was evaluated in this study. Nanofiber-covered stent released paclitaxel (PTX) in controlled manner for 30 days. PTX-NFM significantly inhibited the growth of CT-26 colon cancer in comparison with PTX injection. PTX maintained higher tumor concentrations over 1.0 μg/ml for more than 14 days without systemic exposure. TUNEL and H&E staining proved locally concentrated PTX induced the higher apoptosis than PTX injection. In this way, PTX-eluting nanofiber-covered stent possibly inhibits in-growth of cancer and extends patency of stent. Clinical feasibility of PTX-eluting nanofiber nonvascular stent for cholangiocarcinoma and gastrointestinal cancers will be investigated in further studies. [ABSTRACT FROM AUTHOR]

We previously reported the development of a neutralization assay system for evaluating Japanese Encephalitis Virus (JEV) neutralizing antibody (NAb) using pseudotyped-JEV (JEV-PV). JEV-PV-based neutralization assay offers several advantages compared with the current standard plaque-reduction neutralization test (PRNT), including simplicity, safety, and speed. To evaluate the suitability of the JEV-PV assay as new replacement neutralization assay, we compared its repeatability, reproducibility, specificity, and correlated its results with those obtained using the PRNT. These analyses showed a close correlation between the results obtained with the JEV-PV assay and the PRNT, using the 50% plaque reduction method as a standard for measuring NAb titers to JEV. The validation results m et all analytical acceptance criteria. These results suggest that the JEV-PV assay could serve as a safe and simple method for measuring NAb titer against JEV and could be used as an alternative approach for assaying the potency of JEV neutralization. [ABSTRACT FROM AUTHOR]

Embryonic stem (ES) cells may be used as an alternative source of functionally intact cardiomyocytes for ischemic heart disease. Several natural and synthetic small molecules have been identified as useful tools for controlling and manipulating stem cell renewal and differentiation. Currently, there is an urgent requirement for novel small molecules that specifically induce differentiation of stem cells into cardiomyocytes. To identify compounds that promote cardiomyogenesis of stem cells, cell-based screening of a peptidomimetic small-molecule library was carried out. A series of β-turn peptidomimetic compounds, including CW209E, increased the expression of α-MHC promoter-driven enhanced green fluorescent protein (EGFP) and ratio of beating embryoid bodies (EBs) without inducing cytotoxicity in mouse embryonic stem cells. CW209E also increased the number of beating EBs in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Thus, this chemical compound should be useful for elucidation of the molecular pathway of cardiogenesis and generation of cardiomyocytes ex vivo, which can be further applied for experimental or clinical cell therapy for ischemic heart diseases. [ABSTRACT FROM AUTHOR]

Recently, it was reported that in a 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model, neuronal cell death is associated with the cdk5-mediated hyperphosphorylation of myocyte enhancer factor 2 (MEF2), a transcription factor that is critically required for neuronal survival. In the present study, we investigated the possible involvement of cdk5-mediated MEF2D down-regulation on 6-hydroxydopamine (6-OHDA)-induced PC12 cell death. 6-OHDA was found to significantly increase nitric oxide (NO) production and to induce apoptosis in a time-dependent manner in PC12 cells. Furthermore, 6-OHDA was found to markedly reduce MEF2D levels under conditions that could induce PC12 cell apoptosis. In addition, PC12 cell death and MEF2D degradation by 6-OHDA were prevented by the cdk5 inhibitor roscovitine, but roscovitine could not restore the 6-OHDA-induced inactivation of Akt. These results suggest that the cell death and MEF2D degradation caused by 6-OHDA are dependent on cdk5 activity. On the other hand, roscovitine enhanced the 6-OHDA-induced activations of ERK1/2 and JNK, but reduced the 6-OHDA-induced activation of p38. These results suggest that PC12 cell death by 6-OHDA appears to be regulated by the down-regulation of MEF2D via some interaction between cdk5 and MAP kinase. [ABSTRACT FROM AUTHOR]

Gemcitabine is the only drug approved for single-agent therapy in advanced pancreatic carcinoma (APC). Gemcitabine-based combination chemotherapy has not yet shown promising results. This multicenter phase II study enrolled previously untreated patients with locally advanced and/or metastatic pancreatic adenocarcinoma. Patients received 1,000 mg/m2 gemcitabine, 100-min infusion, day 1 and 100 mg/m2 oxaliplatin, 2-h infusion, day 2; q2w. The primary end point was response rate (RR). Thirteen study centers enrolled 48 eligible patients of which 44 were evaluable. The RR, median overall survival, and median time to progression were 18.2%, 9.4 and 5.6 months, respectively. Sixteen patients (36.4%) experienced clinical benefit. The global quality of life scores improved by 11.71. Grade 3/4 peripheral sensory neuropathy was noted (2.1%), while the most common hematologic toxicity was anemia (grade 3/4, 6.3%). Gemcitabine and oxaliplatin combination chemotherapy showed a promising activity in APC patients and was well tolerated. [ABSTRACT FROM AUTHOR]

The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with advanced gastric cancer. Fifty-seven patients with advanced gastric cancer treated with paclitaxel and cisplatin combination chemotherapy were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue, and the single nucleotide polymorphisms (SNPs) of ten apoptosis-related genes [LTA, TP53, BCL2L11, BID, FASL, caspase 3, caspase 6, caspase 7, and caspase 9] determined using a polymerase chain reaction–restriction fragment length polymorphism assay. The Arg/Pro and Pro/Pro genotypes of TP53 codon 72 were significantly correlated with a lower response rate to the combination chemotherapy when compared to the Arg/Arg genotype (35.7 vs. 66.7%, P-value 0.019) in a logistic regression analysis. A multivariate survival analysis also showed that the time to progression for the patients with the Arg/Pro and Pro/Pro genotypes of TP53 codon 72 was worse than for the patients with the Arg/Arg genotype (Hazard ratio = 3.056, P-value = 0.047), whereas the overall survival was not significantly different. The TP53 codon 72 SNP was found to be predictive of the response to chemotherapy and correlate with the time to progression in patients with advanced gastric cancer treated with paclitaxel and cisplatin chemotherapy. [ABSTRACT FROM AUTHOR]

Unfortunately, the original version of this article contained several errors made during final step of article production. In the results section (fourth sentence) of the Abstract, the incomplete sentence,”, 31.4% in high-risk group and 4.7% in treatment failure group. [ABSTRACT FROM AUTHOR]

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea., Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response., Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients)., Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Background: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea., Methods: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed., Results: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%)., Conclusion: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Background: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA., Methods: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment., Results: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH., Conclusion: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.

Background: We investigated the clinical features and treatment outcomes of patients with mantle cell lymphoma (MCL) in Korea., Methods: We retrospectively analyzed the clinical characteristics and prognosis of 131 patients diagnosed with MCL between January 2004 and December 2009 at 15 medical centers in Korea; all patients received at least 1 chemotherapeutic regimen for MCL., Results: The median age for the patients was 63 years (range, 26-78 years), and 77.9% were men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty-two patients (39.7%) were categorized with high- or high-intermediate risk MCL according to the International Prognostic Index (IPI). Eighteen patients (13.7%) were in the high-risk group according to the simplified MCL-IPI (MIPI). The overall incidence of extranodal involvement was 69.5%. The overall incidence of bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%, respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab were used frequently as the first-line treatment (41.2%). With a median follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%. Multivariate analysis showed that the simplified MIPI was significantly associated with OS. However, the use of a rituximab-containing regimen was not associated with OS and EFS., Conclusion: Similar to results from Western countries, the current study found that simplified MIPI was an important prognostic factor in Korean patients with MCL.