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Supercritical fluid-based extraction technologies are currently being increasingly utilized in high purity extract products for food industries. In recent years, supercritical fluid-based extraction technology is transformed in biomaterials process fields to be further utilized for tissue engineering and other biomedical applications. In particular, supercritical fluid-based decellularization protocols have great advantage over the conventional decellularization as it may allow preservation of extracellular matrix components and structures. In this review, the latest technological development utilizing the supercritical fluid-based decellularization for regenerative medicine is introduced.

Background Human embryonic stem cells (hESCs) transplantation had shown to provide a potential source of cells in neurodegenerative disease studies and lead to behavioral recovery in lentivirus transfected or, toxin-induced Huntington's disease (HD) rodent model. Here, we aimed to observe if transplantation of superparamagnetic iron oxide nanoparticle (SPION)-labeled hESCs could migrate in the neural degenerated area and improve motor dysfunction in an AAV2-Htt171-82Q transfected Huntington rat model. Methods All animals were randomly allocated into three groups at first: HD group, sham group, and control group. After six weeks, the animals of the HD group and sham group were again divided into two subgroups depending on animals receiving either ipsilateral or contralateral hESCs transplantation. We performed cylinder test and stepping test every two weeks after AAV2-Htt171-82Q injection and hESCs transplantation. Stem cell tracking was performed once per two weeks using T2 and T2*-weighted images at 4.7 Tesla MRI. We also performed immunohistochemistry and immunofluorescence staining to detect the presence of hESCs markers, huntingtin protein aggregations, and iron in the striatum. Results After hESCs transplantation, the Htt virus-injected rats exhibited significant behavioral improvement in behavioral tests. SPION labeled hESCs showed migration with hypointense signal in MRI. The cells were positive with βIII-tubulin, GABA, and DARPP32. Conclusion Collectively, our results suggested that hESCs transplantation can be a potential treatment for motor dysfunction of Huntington's disease.

(1) Background and Purpose: Global cerebral ischemia-induced severe hypoxic brain damage is one of the main causes of mortality and long-term neurologic disability even after receiving early blood reperfusion. This study aimed to test the hypothesis that atorvastatin potentially has neuroprotective effects in global cerebral ischemia (GCI). (2) Methods: We performed two sets of experiments, analyzing acute (1-week) and chronic (4-week) treatments. For the vehicle (Veh) and statin treatments, 1 mL of 0.9% saline and 5 mg/kg of atorvastatin (ATOR) were administered orally. For histological analysis, we used the following staining protocols: Fluoro-Jade B and NeuN, 4-hydroxynonenal, CD11b and GFAP, IgG, SMI71, and vWF. Finally, we evaluated the cognitive function with a battery of behavioral tests. (3) Results: The GCI-ATOR group showed significantly reduced neuronal death, oxidative stress, inflammation, and BBB disruption compared with the GCI-Veh group. Moreover, the GCI-ATOR group showed decreased endothelial damage and VV proliferation and had significantly improved cognitive function compared with the GCI-Veh group in both models. (4) Conclusions: ATOR has neuroprotective effects and helps recover the cognitive function after GCI in rats. Therefore, administration of atorvastatin may be a therapeutic option in managing GCI after CA.

Ultra-deep sequencing detects low-frequency genetic mutations with high sensitivity. We used this approach to prospectively examine mutations in the BCR/ABL1 tyrosine kinase from patients with newly diagnosed, chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor nilotinib. Between May 2013 and November 2014, 50 patients from 18 institutions were enrolled in the study. We screened 103 somatic mutations and found that mutations in the P-loop domain were the most frequent (173/454 mutations in the P-loop) and noted the presence of the V299 L mutation (dasatinib-resistant/nilotinib-sensitive) in 98 % of patients (49/50). No patients had Y253H, E255 V, or F359 V/C/I mutations, which would recommend dasatinib rather than nilotinib treatment. The S417Y mutation was associated with lower achievement of a major molecular response (MMR) at 6 months, and the V371A mutation was associated with reduced MMR and MR4.5 durations (MMR for 2 years: 100 % for no mutation vs. 75 % for mutation, P=0.039; MR4.5 for 15 months: 94.1 % vs. 25 %, P=0.002). Patients with known nilotinib-resistant mutations had lower rates of MR4.5 achievement. In conclusion, ultra-deep sequencing is a sensitive method for genetic-based treatment decisions. Based on the results of these mutational analyses, nilotinib treatment is a promising option for Korean patients with CML.

Purpose: This study utilizes the KNV measure to evaluate performance of national pension funds of Korea. Design/methodology/approach: First, this study investigates whether fund managers pick stocks in expansions and time the market in recessions. Second, we examine skilled funds that have both high picking skill in booms and high timing skill in recessions. Third, we examine whether skilled managers have timing ability as well as picking ability. Finally, persistence of skill indexes is investigated. Findings: First, market timing skill is more relevant in recessions whereas stock selection skill is more relevant in expansions. Second, the performance differences between superior and inferior funds are persistent over one-year. Finally, there is no evidence that the same fund managers who display superior stock picking skill in expansions show superior market timing skill in recessions. Research limitations/implications: Since no institutions or organizations provide real-time indicators of the business cycle, switching strategy between timing and picking is not available. Originality/value: This is the first research to analyze the national pension fund using KNV methodology in the Korean market.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRD

BACKGROUND: This study aimed to identify the determinant factors of survival in patients with acute myocardial infarction (AMI) and refractory cardiogenic shock (RCS) who underwent veno-arterial extracorporeal membrane oxygenation (ECMO). METHODS: Sixty-nine consecutive patients with AMI-related RCS were enrolled in the study. They were treated with ECMO and primary percutaneous coronary intervention (PCI). The clinical scores and coronary angiography (CAG) factors related to 100-day survival were evaluated. RESULTS: Thirty patients (43.5%) survived for more than 100 days. The CAG showed that 19 (27.5%) patients had left main disease (LMD). There were 17 (24.6%), 27 (39.1%), and 25 (36.3%) patients with one-vessel, two-vessel, and three-vessel disease, respectively. There were significant differences between the survivors and non-survivors in the simplified acute physiology score II (SAPSII) (65.4±17.2 vs. 83.1±13.0, P

A variety of pathogenic mechanisms, such as cytoplasmic calcium/zinc influx, reactive oxygen species production, and ionic imbalance, have been suggested to play a role in cerebral ischemia induced neurodegeneration. During the ischemic state that occurs after stroke or heart attack, it is observed that vesicular zinc can be released into the synaptic cleft, and then translocated into the cytoplasm via various cation channels. Transient receptor potential melastatin 2 (TRPM2) is highly distributed in the central nervous system and has high sensitivity to oxidative damage. Several previous studies have shown that TRPM2 channel activation contributes to neuroinflammation and neurodegeneration cascades. Therefore, we examined whether anti-oxidant treatment, such as with N-acetyl-l-cysteine (NAC), provides neuroprotection via regulation of TRPM2, following global cerebral ischemia (GCI). Experimental animals were then immediately injected with NAC (150 mg/kg/day) for 3 and 7 days, before sacrifice. We demonstrated that NAC administration reduced activation of GCI-induced neuronal death cascades, such as lipid peroxidation, microglia and astroglia activation, free zinc accumulation, and TRPM2 over-activation. Therefore, modulation of the TRPM2 channel can be a potential therapeutic target to prevent ischemia-induced neuronal death.

Supplemental Digital Content is available in the text, There are limited data regarding the association between brain natriuretic peptide (BNP) levels obtained after weaning from extracorporeal membrane oxygenation (ECMO) and the outcomes of patients with acute coronary syndrome (ACS)-associated cardiogenic shock. We prospectively obtained data regarding patients (aged ≥ 19 years) with ACS-associated cardiogenic shock who received ECMO and were subsequently weaned off the treatment. BNP levels were collected at 5 time points: pre-ECMO implantation, post-ECMO implantation, pre-ECMO weaning, day 1 after ECMO weaning, and day 5 after ECMO weaning. Of 48 patients with ACS-related cardiogenic shock, 33 were included in this analysis. Mean patient age was 59.0 (50.0–66.5) years, and 5 patients (15.2%) were women. Eight patients had asystole/pulseless electrical activity before ECMO and 14 (42.4%) had 3-vessel disease on coronary angiography. During the 6-month follow up, 12 (36.4%) patients died. BNP levels after ECMO weaning were significantly different between 6-month survivors and non-survivors. Cox proportional hazards model revealed that BNP levels (tertiles) on days 1 and 5 after ECMO weaning were significantly associated with 6-month mortality (hazard ratio, 7.872; 95% confidence interval, 1.870–32.756; 8.658 and 1.904–39.365, respectively). According to the Kaplan–Meier curves, the first tertile had significantly longer survival compared to the third tertile for both days 1 and 5 after ECMO weaning. Post-ECMO weaning BNP levels (days 1 and 5) were significantly associated with increased 6-month mortality in patients with ACS complicated by refractory cardiogenic shock who were weaned off ECMO.

Background/Aims: A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe tox icities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary compli cations in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity. Methods: We retrospectively reviewed the medical records and chest image find ings of 644 patients who were treated with targeted antineoplastic agents at Soon chunhyang University Hospital between May 2005 and September 2014. Results: Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontin ued in all patients, while 11 patients were simultaneously treated with glucocorti coids. Three patients died of drug-related pulmonary toxicity. Conclusions: During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontin uing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.

Introduction The heart rate is a basic indicator of the state of the human body and therefore it is important to measure the heart rate continuously, reliably, and accurately. However, it is difficult to measure the heart rate in various environments due to the limitations of Contact sensors, such as ECG. Therefore, heart rate measurement using non-contact sensors such as PVDF, Radar, and cameras has been widely studied. Among these non-contact sensors to measure the heart rate, the PVDF sensor, installed under a bed or chair, can measure the heart rate from the J-peak of Ballistocardiograph (BCG). However, it is challenging to accurately measure the heart rate due to noise-induced by the external environment. To overcome these challenges in this study, we have proposed a new algorithm for accurate heart rate measurement using PVDF sensor. The proposed algorithm includes estimators and clustering techniques to estimate the beat-to-beat of BCG signals. Methods In order to continuously estimate inter-beat interval, basic, auto-correlation, average magnitude difference function, maximum amplitude pairs, and a Bayesian approach are used to obtain basic information to calculate inter-beat interval. Auto-correlation is an estimator that estimates heart rate intervals by calculating for all discrete lags. The average magnitude difference function (AMDF), which is often used for pitch tracking, also calculates for discrete lags like auto-correlation. If the waveforms of BCG are similar, the calculated value with AMDF is small. Therefore, the reciprocal of the ADMF output is used to take the larger value for the most likely interval. This is a complementary relationship from auto-correlation because the noise characteristics are different. Maximum amplitude pairs is an estimator used for indirect peak detectors with the amplitude information of the signal. The estimated IBI was determined by combining the estimation results of three estimators with a Bayesian approach. After the estimated IBI was obtained, continuously estimated inter-beat intervals were clustered into locally similar values. The inter-beat interval values were determined by voting for the most estimated interval value in the clustered sets.All inter-beat intervals estimated by the Bayesian method have their own probability density function and the confidence value was calculated using the difference between the largest peak and the second largest peak of the probability density function. By excluding inter-beat intervals with low confidence values, the accuracy of the estimation was improved. After, the final continuous inter-beat intervals were calculated by performing the ectopic beats removal algorithm and interpolation. Results To evaluate the performance, BCG data from PVDF sensor was simultaneously measured with PSG. The PSG datasets consisted of three male patients with moderate sleep apnea, a patient with snoring problems, and a normal person. Because of the difference in timing between the peak signal of ECG and that of BCG, less than 1 HR count was allowed when the inter-beat intervals were converted to HR. When the 21-hour inter-beat intervals were compared, the difference in HR was less than 1 in 91.4%. The rest 8.6% had a difference of 1 HR or more, and it was confirmed that 6.9% of them were caused by movement, and the remaining 1.7% were caused by a temporary failure of the sensor. Conclusion The proposed algorithm showed better coverage by 18.71% compared to the coverage of 72.69% from the previous study. It was confirmed that the proposed algorithm provides a more accurate heart rate than previous studies, and the measured inter-beat intervals will be used to estimate, not only the heart rate but also the sleep stage in the future. Support (If Any)

Aim Cytotoxic chemotherapy-based treatment of multiple myeloma (MM) is not curative, and the disease eventually recurs. This is partially because although currently available anti-MM strategies are effective in targeting the bulk of tumor cells, they do not target the tumor-initiating subpopulation of cancer stem cells. This study investigated the prevalence and biological functions of side population (SP) cells in MM cell lines including RPMI8226, ARH77, MM.1R and IM 9. Materials and methods Flow cytometry-based Hoechst 33342 staining was used to evaluate the existence of SP cells. In addition, the ability of SP cells to regenerate the original population was determined. Results The frequency of SP cells was heterogeneous. Most cell lines (ARH77, IM9, and MM.1R) contained fewer than 1% SP cells; however, RPMI8226 contained approximately 10% SP cells. Sorted SP cells showed a higher proliferative ability and clonogenicity than the MP in the RPMI8226 myeloma cell line. The activity of ATP-binding cassette subfamily G member 2 (ABCG2), which is associated with high rates of proliferation, was higher in SP cells. However, the expression of specific surface markers such as cluster of differentiation (CD)138, CD34, CD38, CD19, CD20, and CD27 did not differ between SP and MP cells. Bortezomib was the only agent that significantly affected proliferation of both SP and MP cells. Conclusion Our studies demonstrated that the SP fraction of myeloma cells possessed clonogenic tumor-initiating potential and revealed new mechanisms of action for bortezomib on SP cells.

When existing Reinforced Concrete (RC) framed structures are strengthened with Precast Concrete (PC) wall panels, a special connection is required that can accommodate the time-dependent deformation of the RC frame when using PC members made of the same size and resist a large shear force. In this study, we propose a connection that can solve both of these issues through overlapping anchors. The purpose of this study is to investigate and analyze the shear resistance of the overlapped anchor connections between the PC panel and the RC elements in modeling tests. A total of ten full-scale specimens of anchored connection models were constructed and push-out tested. Two anchor groups were installed in three concrete segments and overlapped in the connection of the specimens. The tested average shear strength of the overlapped anchored connections was 109% of the calculated values according to the American anchor design code. The results of this study show that the new anchored connection model can be analyzed using the American anchor design code. Therefore, we can predict the effect of the proposed connection, and it is expected that the design safety and construction practicability of the infill method will be improved using these connections.

Purpose Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). Materials and methods This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed. Results Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naive patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common. Conclusion Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naive benefitted from dovitinib.

An increase in the ratio of the brachial pre-ejection period to brachial ejection time [pre-ejection period (PEP)/ET] is correlated with a decrease of left ventricular ejection fraction (LVEF). The current study was designed to test the hypothesis that the change value (Δ) of PEP/ET is a useful indicator of Δ LVEF in patients with left ventricular systolic dysfunction.We consecutively enrolled 104 patients with left ventricular systolic dysfunction (LVEF < 45%). PEP/ET, B-type natriuretic peptide (BNP), and LVEF were evaluated at baseline and at 6-month follow-up. Compared with the baseline measurements, the 6-month values of ΔLVEF, ΔBNP, and ΔPEP/ET were 9.8% ± 9.0% (from 36.3% ± 9.2% to 46.3% ± 12.5%, P < 0.001), -168.5 ± 255.4 (from 271.4 ± 282.5 to 104.1 ± 129.6, P < 0.001), and -0.060 ± 0.069 (from 0.413 ± 0.097 to 0.358 ± 0.079, P < 0.001), respectively. There were significant correlations between LVEF and PEP/ET and between LVEF and BNP in both the initial (r = -0.316, P = 0.001 and r = -0.598, P < 0.001, respectively) and 6-month follow-up (r = -0.307, P = 0.003 and r = -0.701, P < 0.001, respectively). The Steiger's Z test showed that BNP had a significantly stronger correlation with LVEF compared with the correlations between LVEF and PEP/ET in both the initial and 6-month studies (Z = 2.471, P = 0.013 and Z = 3.575, P < 0.001, respectively). There were also significant correlations between ΔLVEF and ΔPEP/ET (r = -0.515, P < 0.001) and between ΔLVEF and ΔBNP (r = -0.581, P < 0.001); however, there was no difference between the correlations for ΔLVEF and ΔPEP/ET versus ΔLVEF and ΔBNP (Steiger's Z = 0.600, P = 0.545).In patients with left ventricular systolic dysfunction not only ΔBNP but also ΔPEP/ET could be a simple indicator of predicting change of LVEF.

The purpose of this study is to investigate the behavior of existing Reinforced Concrete (RC) frames strengthened with L-type Precast Concrete (PC) wall panels under cyclic loads. The idea is to remove the brick walls with windows inside the RC frames and to strengthen the frames using L-type PC wall panels, thus transforming the existing brick infill into a strong and rigid PC infill. Herein, a technique using dowels (i.e. post-installed anchors) to fix a PC wall panel firmly to a RC frame is proposed. This technique is to anchor dowels through pre-installed holes in a PC wall panel. A total of six full-scale, one-bay, one-story RC frames were constructed and tested under reverse cyclic loading. Four L-type PC wall panels with large openings were used for strengthening the RC frames. As a result, the lateral strength, stiffness, and energy dissipation capability of the frame was greatly improved. Specifically, the more dowels that were used to fix the vertical part of a PC wall panel to an RC column and the thicker the PC wall panel, the better the seismic resistance of the frame.

Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR 4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR 4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR 4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR 4, and MR 4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.