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Abstract Evaluating fluid responsiveness with dynamic parameters is recommended for fluid management. However, in hemodynamically stable patients who are breathing spontaneously, accurately measuring stroke volume variation via echocardiography and passive leg raising is challenging due to subtle SV changes. This study aimed to identify normal SV changes in healthy volunteers and evaluate the precision of hemodynamic parameters in screening mild hypovolemia in patients. This prospective, repeated-measures, cross-sectional study screened 269 subjects via echocardiography. Initially, 45 healthy volunteers underwent a fluid challenge test, the outcomes of which served as criteria to screen 215 ICU patients. Among these patients, 53 underwent additional fluid challenge testing. Hemodynamic parameters, including medians of maximum velocity time integrals (VTImaxs), peak velocity of VTImax (PV), internal jugular vein diameters (IJVD), and area (IJVA) were repeatedly measured first at a 60° upper body elevation (UBE), second in a supine position, third at UBE, fourth in a supine position, and lastly in a supine position after fluid loading. The hemodynamic responses to the position changes were compared between 83 fluid non-responders and 15 fluid responders. Fluid responsiveness was defined as fluid-induced medians’ change of VTImaxs (fluid-induced median VTImax change) ≥ 10%. None of the healthy volunteers showed the mean value of repeatedly measured medians of VTImaxs ≥ 7%, following either UBE position (UBE-induced median VTImax change) or fluid loading (fluid-induced median VTImax change). UBE-induced median VTImax and PV changes were significantly correlated with fluid responsiveness (p

PURPOSE This study aimed to validate the effect of core-based exercise on proprioception in individuals with neurological disorders through a systematic review and meta-analysis. METHODS A systematic literature search was conducted using databases such as PubMed, Web of Science, and Scopus for studies published up to October 10, 2023. The search yielded 1,945 articles, with seven studies ultimately included for in-depth analysis. Meta-analysis was performed using Review Manager 5.4 software. Standardized mean differences (SMDs) were calculated using Hedges’ g value using both random-effects and fixed-effects models. RESULTS The meta-analysis revealed that core-based exercise significantly improved joint position sense (SMD=-1.33; 95% confidence interval [CI]=-2.09 to −0.57; I²=0%; p

PURPOSE This study aimed to prove the mediator effect of skill level on participation frequency and injury level of leisure sports players with the highest injury rate. METHODS Raw data of the “2019 Sports Safety accident data” conducted by the Korea Sports Safety Foundation were used for this study. We analyzed 857 leisure sports players participating in events with the top four highest injury rates (Basketball, Soccer, Baseball/Softball, Foot Volleyball). Frequency, descriptive statistics, and correlation analyses using SPSS version 27.0 and Process macro model 4 were employed for analysis. RESULTS The results regarding participation frequency, injury severity, and skill level among recreational athletes are as follows. First, a positive correlation was established between the participation frequency of recreational athletes and their skill levels. Second, the correlation between participation frequency and injury severity was observed only in soccer and basketball. Third, skill level plays a mediating role in the relationship between participation frequency and injury level. The results indicate that as the participation frequency among leisure sports players who participate in ball sports with a high injury rate increases, this affects the degree of injury. CONCLUSIONS Skill level appears to play a mediating role in the relationship between participation frequency and injury level. Based on the results, we recommend safety education not only on the relationship between participation frequency and injury level, but also the intermediary role of skill level.

Abstract Background Plant scientists have largely relied on pathogen growth assays and/or transcript analysis of stress-responsive genes for quantification of disease severity and susceptibility. These methods are destructive to plants, labor-intensive, and time-consuming, thereby limiting their application in real-time, large-scale studies. Image-based plant phenotyping is an alternative approach that enables automated measurement of various symptoms. However, most of the currently available plant image analysis tools require specific hardware platform and vendor specific software packages, and thus, are not suited for researchers who are not primarily focused on plant phenotyping. In this study, we aimed to develop a digital phenotyping tool to enhance the speed, accuracy, and reliability of disease quantification in Arabidopsis. Results Here, we present the Arabidopsis Disease Quantification (AraDQ) image analysis tool for examination of flood-inoculated Arabidopsis seedlings grown on plates containing plant growth media. It is a cross-platform application program with a user-friendly graphical interface that contains highly accurate deep neural networks for object detection and segmentation. The only prerequisite is that the input image should contain a fixed-sized 24-color balance card placed next to the objects of interest on a white background to ensure reliable and reproducible results, regardless of the image acquisition method. The image processing pipeline automatically calculates 10 different colors and morphological parameters for individual seedlings in the given image, and disease-associated phenotypic changes can be easily assessed by comparing plant images captured before and after infection. We conducted two case studies involving bacterial and plant mutants with reduced virulence and disease resistance capabilities, respectively, and thereby demonstrated that AraDQ can capture subtle changes in plant color and morphology with a high level of sensitivity. Conclusions AraDQ offers a simple, fast, and accurate approach for image-based quantification of plant disease symptoms using various parameters. Its fully automated pipeline neither requires prior image processing nor costly hardware setups, allowing easy implementation of the software by researchers interested in digital phenotyping of diseased plants.

Abstract Postoperative pancreatic fistula is a life-threatening complication with an unmet need for accurate prediction. This study was aimed to develop preoperative artificial intelligence-based prediction models. Patients who underwent pancreaticoduodenectomy were enrolled and stratified into model development and validation sets by surgery between 2016 and 2017 or in 2018, respectively. Machine learning models based on clinical and body composition data, and deep learning models based on computed tomographic data, were developed, combined by ensemble voting, and final models were selected comparison with earlier model. Among the 1333 participants (training, n = 881; test, n = 452), postoperative pancreatic fistula occurred in 421 (47.8%) and 134 (31.8%) and clinically relevant postoperative pancreatic fistula occurred in 59 (6.7%) and 27 (6.0%) participants in the training and test datasets, respectively. In the test dataset, the area under the receiver operating curve [AUC (95% confidence interval)] of the selected preoperative model for predicting all and clinically relevant postoperative pancreatic fistula was 0.75 (0.71–0.80) and 0.68 (0.58–0.78). The ensemble model showed better predictive performance than the individual ML and DL models.

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.

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Background: Distinguishing between large-vessel diseases such as acute aortic syndrome (AAS) and pulmonary embolism (PE), and non-large-vessel diseases, such as acute coronary syndrome (ACS), heart failure (HF), and neurogenic diseases, in patients presenting with chest symptoms remains a challenge, which can result in a significant number of misdiagnoses. Simultaneously distinguishing both AAS and PE is essential because large-vessel diseases require angio-computed tomography (CT) during initial presentation whereas, non-large-vessel diseases do not. This study aimed to determine the optimal method for differentiating between large-vessel and non-large-vessel diseases using D-dimer, troponin I, and pretest probability scores. Methods: From the 11683 patients who presented with chest symptoms including chest pain, discomfort, or dyspnea, this retrospective observational study included 1817 patients who had complete data for essential biomarkers; 105 with AAS, 139 with PE, 1093 with ACS, 451 with HF, and 83 with neurogenic diseases. Results: D-dimer, D-dimer/troponin I ratio (DT ratio), and troponin I results distinguished the 2 groups: D-dimer (>2.38 μg/mL), AUC 0.935; DT ratio, AUC 0.827; and troponin I, AUC 0.653. For predicting AAS, the performances of D-dimer level and aortic dissection detection risk score (ADD-RS) were AUCs of 0.915 (p

Abstract This study aimed to select the optimal microbial agents for ammonia gas reduction in Chinese cabbage cultivation and evaluate their ammonia reduction efficiency. By selecting the optimum microorganism to reduce ammonia emissions, the ammonia emission reduction efficiencies of the nitrification microorganisms, Alcaligenes faecalis subsp. faecalis and Brevibacillus sp. were 21 and 31%, respectively, which were superior to those of other microorganisms. The best ammonia emission reduction efficiency of the acid-producing microorganisms was 55%. The optimum mixing ratio of microbial agent for removing ammonia gas emitted from NPK-containing soil was: acid-producing microorganism:Alcaligenes faecalis subsp. faecalis:Brevibaillus sp. = 0.70:0.15:0.15. The optimum treatment amount was 500 L/ha, and the optimum number of microbial agents was basal fertilization (also known as pre-planting fertilization) once and additional fertilization three times, for a total of four times. The reduction efficiency of ammonia emissions from NPK-containing soil under optimum conditions in cabbage cultivation was 27% lower than that of the control (only NPK-containing soil). Therefore, the microbial agent developed in this study can be utilized to effectively reduce the emission of ammonia, a secondary fine particle precursor, while maintaining crop yield in agricultural fields.

PURPOSE The first purpose of this study is to investigate the relationship between Post-Stroke Respiratory Sarcopenia (PSRS) and Cognitive Impairment (CI) through Breathing Exercise (BE) as a respiratory rehabilitation after stroke (ST). The second purpose is to introduce a pilot study design set to investigate and compare the acute effects of each BE to develop a BE protocol for further studies. METHODS Pubmed, Scopus, Web of Science and Google Scholar search engines were used to identify the definition and mechanism of ST, CI and respiratory sarcopenia (RS), and to find cases of application of BE in such conditions. RESULTS Review; BEs that improve ST, RS, and CI symptoms are Box Breathing (Tactical Breathing), Fast-Breathing, Slow-paced Breathing, Inspiratory Diaphragmatic Breathing+Expiratory Pursed-lip Breathing Exercise. However, the effect is still unclear as post-stroke patients undergo multiple medical treatments other than BE. Pilot Study Prospective results; Inspiratory Diaphragmatic Breathing+Expiratory Pursed-lip Breathing Exercise, Slow-paced Breathing, Box Breathing (Tactical Breathing) and Fast-Breathing will be performed by 40 healthy college students through a randomized controlled trial for 4 weeks. Respiratory functions, exercise intensity, active oxygen level, blood lactate level, cerebral oxygen saturation and cognitive function will be measured pre- and post-intervention along with acute and 2 week mid-intervention. BEs are expected to improve respiratory function, cognitive performance and energy levels while reducing HR, BP, and stress. However, individual response to BE may vary according to health, physical fitness and life styles. All BE will be conducted in an evenly controlled and supervised environment for accurate data collection. CONCLUSIONS Further study will be done to develop an appropriate BE protocol for PSRS patients per this review. Follow-up studies may also use this review as a reference for the application of BEs in PSRS patients with CI.

Abstract Analyzing volatile organic compounds (VOCs) in food is crucial but challenging. Schisandra chinensis Baillon (omija) is an herbal plant with various functional health activities. Previous VOC analyses focused on S. chinensis fruit but not its leaves. Therefore, VOCs in S. chinensis fruit and leaves were analyzed using headspace stir‐bar sorptive extraction (HS‐SBSE)‐GC–MS, and optimal conditions were established. Various factors, such as the sample preparation method, twister stir‐bar type, sample amount, extraction temperature, and extraction time, expected to affect extraction were carefully optimized. Under the optimal conditions, 35 and 40 VOCs were identified in S. chinensis fruit and leaves, respectively. This HS‐SBSE method is capable of rapid analysis and a low contamination rate without requiring organic solvents. These findings provide practical guidelines for HS‐SBSE applications in various food matrices by providing analytical methods for VOC detection.

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.

Characteristics of random ocean waves have been measured by different devices, and X-band marine radar is one of the typical devices. This study proposes an enhanced methodology for estimating the significant wave height of ocean waves through the analysis of X-band radar images, particularly leveraging the shadowing characteristics inherent within radar images. The enhancement of the shadowing-based algorithm is achieved by incorporating three different key physical properties of ocean waves. These include the spatial autocorrelation function (SACF) in the Smith function, the orthogonal property of mean surface slopes, and the relationship of high-order spectral moments. The enhanced algorithm is complementarily integrated with fast Fourier transform (FFT)-based spectral analysis, facilitating the determination of significant wave height without the necessity for supplementary reference measurements. Numerical tests have been conducted using synthetic and real radar images corresponding to various sea states to validate the accuracy and reliability of the proposed methodology. The results demonstrate that the proposed techniques consistently improve the estimation accuracy of significant wave heights for both synthetic and real radar images. Even though the measured real radar images used for validation are not exhaustive in terms of the amount of dataset and range of sea state severity, considering that the proposed technique is in its early development stage, it is inspiring that its effectiveness and physical validity have been demonstrated through the present study.

Abstract Background To develop a new algorithm to differentiate ventricular tachycardia (VT) from preexcited tachycardia (pre‐ET) according to left bundle branch block (LBBB) and right bundle branch block (RBBB) patterns. Methods This study included 67 electrocardiograms (ECGs) with VT and 63 ECGs with pre‐ET, collected from our hospital and through PubMed. Of those, 64 were allocated to the derivation cohort and the rest to the validation cohort. The diagnoses of the ECGs were confirmed using an electrophysiological study. Parameters and classifiers from prior algorithms along with the propagation speeds in the early portion of the QRS complex (initial deflection index) in leads V1, V6, aVR, II, and III were manually measured. The performance of the new algorithm was compared with that of prior algorithms. Results The initial deflection index in lead III was the strongest predictor of pre‐ET in LBBB‐pattern wide‐QRS tachycardia (p = 0.003, AUC 0.805). The initial deflection index in lead V1 was the most powerful predictor of pre‐ET in RBBB‐pattern wide‐QRS tachycardia (p = 0.001, AUC 0.848). Compared to earlier algorithms, those using the initial deflection indexes: lead III in LBBB patterns (cutoff value >0.3) and lead V1 in RBBB patterns (cutoff value ≤0.48), demonstrated superior performance in screening VT, with AUC values of 0.828. The initial deflection indexes proved effective as discriminators between VT and pre‐ET in the validation cohort. Conclusions In LBBB‐pattern wide‐QRS tachycardia, the early propagation speed of pre‐ET was faster than that in VT. Conversely, in RBBB‐pattern wide‐QRS tachycardia, it was slower.

This multicentre, phase II study of the Australian Lymphoma and Leukaemia Group (ALLG) and the Asian Myeloma Network (AMN) investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d; KTd) in patients with relapsed and/or refractory multiple myeloma and 1-3 prior lines of therapy. Patients received induction with up to twelve 28-day cycles of K [20mg/m2 IV cycle 1 day 1 and 2, 56mg/m2 (36mg/m2 for patients ≥75 years) from day 8 onwards), T 100mg PO nocte and weekly dexamethasone 40mg (20mg for patients ≥75 years). During maintenance T was omitted, while K continued on days 1,2,15,16 with fortnightly dexamethasone. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate, overall survival (OS), duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years (41.9 – 84.5)) were enrolled with a median follow-up of 26.4 (1.6 – 54.6) months. The median PFS was 22.3 months (95% CI 15.7 – 25.6) with a 46.3% (95% CI 35.1 – 52.8) 2-year PFS. Median OS was not reached and was 73.8% (95% CI 62.9 – 81.9) at 2 years. The overall response rate was 88% (≥ VGPR 73%). There was no difference in the depth of response, PFS or OS comparing Asian and Non-Asian cohorts (p=0.61). The safety profile for KTd was consistent with each individual drug. KTd is well tolerated and effective in patients with RRMM irrespective of Asian or non-Asian ethnicity and provides an alternative option particularly where use of KRd is limited by access, cost, or renal impairment.

Background: The impact of cerebral edema on brain cells and ventricles in cardiac arrest patients can manifest as effacement of cortical sulci, diminished ventricle size, altered gray matter to white matter ratio (GWR), and increased optic nerve sheath diameter (ONSD) in brain CT scans. However, a complete investigation of GWR in whole lobes, quantitative cistern size, and comprehensive comparison of various brain CT parameters has not been conducted. This study aimed to comprehensively compare various early brain CT parameters along with conventional significant variables in relation to poor neurological outcome and diffuse cortical necrosis. Methods: This retrospective study included 86 adult patients with cardiac arrest who underwent brain CT/MRI. GWRs, the distance of the posterior ambient cistern, and ONSD in early brain CT and regions of interest (ROIs) in brain MRI were measured and analyzed along with clinical characteristics. Results: ROIs in the putamen and parietal white matter showed significant differences (p = 0.05, p = 0.022, respectively). The distance of the posterior ambient cistern and the GWR of the putamen and parietal white matter were newly developed predictors that were not used previously and demonstrated a significant correlation with the presence of diffuse cortical necrosis (OR 0.4, p = 0.006, AUC 0.637; OR 0.478, p = 0.02, AUC 0.603, respectively) or poor neurological outcomes (AUC 0.637, AUC 0.603, respectively), but were not more significant than pupil reflex (OR 0.06, p

Objective This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET). Methods Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16–18) or MSP (cycle days 19–21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups. Results Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group. Conclusion Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.

Highly malignant electroencephalogram (EEG) patterns (including suppressed background and burst suppression) refer to a poor neurological outcome in cardiac arrest patients, but some of those patients may show a good neurological outcome. This is the first report that details the reason for their uncommon survival despite highly malignant EEG patterns after cardiac arrest. The brain cortical activities in very elderly patients (who are vulnerable to the usual sedative doses) showed a suppressed background and burst suppression but resulting in a good neurological outcome. The mean suppression rates from their EEGs were 100% and 68.4%, respectively, and a normal pattern was completely restored after the sedatives had affected their brain waves for 12 hours. It was speculated that sedatives given at an ordinary dose may negatively affect the brain’s cortical activity in elderly patients who demonstrate a good neurological outcome. When appropriate doses of sedatives are used, highly malignant EEG patterns in very elderly patients should be carefully interpreted for early neuroprognostication.

Abstract This study aimed to identify the benefits of autologous-stem cell transplantation (auto-SCT) and allogeneic-SCT (allo-SCT) in patients with aggressive T-cell lymphomas to aid in the selection of transplantation type in clinical practice. This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 patients underwent up-front SCT as consolidation therapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 68.7% and 76.1%, respectively. Patients who underwent auto-SCT had significantly better OS (p = 0.026) than those who underwent allo-SCT; however, no statistical difference in PFS was found. Transplantation was used as a salvage therapy in 188 patients who had relapsed/refractory disease. Overall, 96 (51.1%) patients underwent auto-SCT and 92 (48.9%) patients underwent allo-SCT. Auto-SCT improved long-term survival in patients with complete remission (CR). Allo-SCT demonstrated better 3-year PFS in patients with partial remission and relapsed/refractory disease status. However, >50% of patients died within 1 year of allo-SCT. As a consolidative therapy, up-front auto-SCT demonstrated a survival benefit. Auto-SCT was also effective in patients who achieved CR after salvage therapy. If the disease persists or cannot be controlled, allo-SCT may be considered with reduced intensity conditioning.

Abstract Background Myosteatosis and systemic inflammation are well‐known prognostic factors in patients with colorectal cancer (CRC). The serum albumin level is a reflection of malnutrition and systemic inflammation, which in turn plays a key role in the development of myosteatosis. However, few studies have been conducted on these synergistic effects. This study aimed to examine the individual and synergistic effects of different prognostic markers related to skeletal muscle quality and serum albumin levels in patients with CRC. Methods This study enrolled patients with stage I–III CRC who underwent surgical resection between July 2006 and February 2014. Skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) were calculated using computed tomography at the L3 level obtained within 2 months prior to surgery. The albumin‐myosteatosis gauge (AMG) was defined as SMD × albumin. Patients were divided into sex‐specific quartiles (G1 to G4) according to the AMG, and analysis of variance for continuous variables and chi‐square test for categorical variables were used to compare variables among quartiles. Cox proportional hazard models were constructed and integrated receiver operating characteristic curve (iAUC) analysis was used to compare the prognostic performance of SMD, albumin and AMG. Results Among the 906 participants, the median (interquartile) age was 64 (55–72) years, and 365 (40.3%) were female. AMG was significantly correlated with the occurrence of complications, albumin level, SMI and SMD (all P

Damage to the intestinal barrier causes intestinal inflammation, which could lead to the development of gastrointestinal diseases. Nut oils contain an abundance of unsaturated fatty acids, which are responsible for most of the bioactivities of nut oils. Here, the protective effect of four nut oils on the intestinal epithelial barrier was confirmed using Caco-2 cells damaged by tumor necrosis factor-α/interferon-γ treatment. Nut oils effectively increased transepithelial electronic resistance and lowered paracellular fluorescein isothiocyanate-dextran permeability in damaged Caco-2 cells. Furthermore, the nut oils inhibited the pro-inflammatory cytokine production of interleukin-6, which was induced by the inflammatory response. In particular, walnut oil effectively improved tight junction protein (occludin and zonula occludens-1) expression and distribution in damaged Caco-2 cells. In conclusion, our findings suggest that nut oils are promising candidates for impaired intestinal barrier protection.

IntroductionPegylated granulocyte colony-stimulating factor (G-CSF) has been widely used for preventing febrile neutropenia in various types of cancer treatment. In the present study, we prospectively evaluated the safety and efficacy of pegfilgrastim as a primary prophylaxis of febrile neutropenia and infection among patients with relapsed refractory multiple myeloma (RRMM) treated with pomalidomide-based regimens.MethodsThirty-three patients with RRMM who received pomalidomide and dexamethasone (Pd) with or without cyclophosphamide (PCd) were enrolled in this study. Twenty-eight patients were treated with PCd and 5 patients were treated with Pd. All patients were given pegfilgrastim subcutaneously with a single administration performed on the first day of each cycle as primary prophylaxis until the fourth cycle.ResultsThe median age of the patients was 75 (range 56-85), and the median prior line of therapy was 2 (range 2-6). Seventeen patients (51.5%) had any grade of neutropenia and 20 (60.6%) had any grade of thrombocytopenia before starting pomalidomide treatment. During the 4 cycles of treatment, grade 3 or more neutropenia occurred in 17 patients (51.5%), and 4 (12.1%) experienced grade 3 or more febrile neutropenia. Grade 3 or more infections occurred in 5 patients (15.2%). Interestingly, the patients with markedly increased ANC of more than 2 x 109/L compared to baseline ANC after 7 days of pegfilgrastim at 1st cycle of treatment showed a significantly lower incidence of grade 3-4 neutropenia. The most common adverse event of pegfilgrastim was fatigue, and all the adverse events caused by pegfilgrastim were grade 1 or 2. And there was no significant change in the immune cell population and cytokines during the administration of pegfilgrastim.DiscussionConsidering that this study included elderly patients with baseline neutropenia, pegylated G-CSF could be helpful to prevent severe neutropenia, febrile neutropenia, or infection in patients with RRMM.

Candidate strains that contribute to drought resistance in plants have been previously screened using approximately 500 plant growth-promoting rhizobacteria (PGPR) obtained from Gotjawal, South Korea, to further understand PGPR associated with plant drought tolerance. In this study, a selected PGPR candidate, Flavobacterium sp. strain GJW24, was employed to enhance plant drought tolerance. GJW24 application to Arabidopsis increased its survival rate under drought stress and enhanced stomatal closure. Furthermore, GJW24 promoted Arabidopsis survival under salt stress, which is highly associated with drought stress. GJW24 ameliorated the drought/salt tolerance of Brassica as well as Arabidopsis, indicating that the drought-resistance characteristics of GJW24 could be applied to various plant species. Transcriptome sequencing revealed that GJW24 upregulated a large portion of drought- and drought-related stress-inducible genes in Arabidopsis. Moreover, Gene Ontology analysis revealed that GJW24-upregulated genes were highly related to the categories involved in root system architecture and development, which are connected to amelioration of plant drought resistance. The hyper-induction of many drought/salt-responsive genes by GJW24 in Arabidopsis and Brassica demonstrated that the drought/salt stress tolerance conferred by GJW24 might be achieved, at least in part, through regulating the expression of the corresponding genes. This study suggests that GJW24 can be utilized as a microbial agent to offset the detrimental effects of drought stress in plants.

Background Predicting the length of stay (LOS) for coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is essential for efficient use of ICU resources. We analyzed the clinical characteristics of patients with severe COVID-19 based on their clinical care and determined the predictive factors associated with prolonged LOS. Methods We included 96 COVID-19 patients who received oxygen therapy at a high-flow nasal cannula level or above after ICU admission during March 2021 to February 2022. The demographic characteristics at the time of ICU admission and results of severity analysis (Sequential Organ Failure Assessment [SOFA], Acute Physiology and Chronic Health Evaluation [APACHE] II), blood tests, and ICU treatments were analyzed using a logistic regression model. Additionally, blood tests (C-reactive protein, D-dimer, and the PaO2 to FiO2 ratio [P/F ratio]) were performed on days 3 and 5 of ICU admission to identify factors associated with prolonged LOS. Results Univariable analyses showed statistically significant results for SOFA score at the time of ICU admission, C-reactive protein level, high-dose steroids, mechanical ventilation (MV) care, continuous renal replacement therapy, extracorporeal membrane oxygenation, and prone position. Multivariable analysis showed that MV care and P/F ratio on hospital day 5 were independent factors for prolonged ICU LOS. For D-dimer, no significant variation was observed at admission; however, after days 3 and 5 days of admission, significant between-group variation was detected. Conclusions MV care and P/F ratio on hospital day 5 are independent factors that can predict prolonged LOS for COVID-19 patients.

Vision: bringing the two sides together A protein regulating gene expression called Vax1 is essential for building the optic chiasm (OC), a brain structure where nerves from the left and right eyes cross to the other side of the brain. Signals from both eyes must be integrated for space and depth perception. Although some cues guiding optic nerve growth are known, those for the OC are not. Jin Woo Kim at the Korea Advanced Institute of Science and Technology, Daejeon, South Korea, and co-workers investigated visual development in mice expressing a mutant Vax1. They found that the mutant Vax1 could not support the optic nerve, which grew slowly and failed to connect to the other side of the brain. Consequently, the mice had impaired depth perception and low vision. These results show the importance of Vax1 for the development of binocular vision.

Cultured meat production relies on various cell types, including muscle stem cells (MuSCs), embryonic stem cell lines, induced pluripotent cell lines, and naturally immortalized cell lines. MuSCs possess superior muscle differentiation capabilities compared to the other three cell lines, making them key for cultured meat development. Therefore, to produce cultured meat using MuSCs, they must first be effectively separated from muscles. At present, the methods used to isolate MuSCs from muscles include (1) the pre-plating method, using the ability of cells to adhere differently, which is a biological characteristic of MuSCs; (2) the density gradient centrifugation method, using the intrinsic density difference of cells, which is a physical characteristic of MuSCs; and (3) fluorescence- and magnetic-activated cell sorting methods, using the surface marker protein on the cell surface of MuSCs, which is a molecular characteristic of MuSCs. Further efficient and valuable methods for separating MuSCs are expected to be required as the cell-based cultured meat industry develops. Thus, we take a closer look at the four methods currently in use and discuss future development directions in this review.

Ecklonia cava, a brown seaweed native to the East Asian coast, is known for its unique composition, including polysaccharides, polyphenols, and phlorotannins. Fucoidan is a sulfated polysaccharide widely used as a functional ingredient in foods. This study obtained crude polysaccharides (ECC_CPS) from E. cava celluclast enzymatic hydrolysate using ethanol precipitation. ECC_CPS increased cell viability during the proliferation of Hanwoo muscle satellite cells (HMSCs). The effect of ECC_CPS on the expression of proliferation-related markers was confirmed as MYF5 and MYOD expression significantly increased, whereas PAX7 expression was maintained. The evaluation of cell migration activity has a major impact on cell proliferation and differentiation, and the cell migration index significantly increased with ECC_CPS treatment (p < 0.01). This was related to the HGF/MET pathway and FAK pathway. Treatment with ECC_CPS promoted differentiation at the cell differentiation stage, thereby increasing the expression of differentiation markers, such as MYH2, MYH7, and MYOG (p < 0.001 or p < 0.01). Therefore, our findings imply that crude polysaccharide obtained from E. cava can be an additive ingredient that enhances the proliferation and differentiation of muscle satellite cells used in the manufacture of cultured meat products.

Background: We aimed to analyze the correlation between in-hospital mortality and hemodynamic changes, using polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) initiation time in patients with cancer with refractory septic shock. Methods: Forty-six patients with cancer who received PMX-DHP for refractory septic shock were retrospectively analyzed and classified into early (≤3 h between refractory septic shock and PMX-DHP; n = 17) and late (>3 h; n = 29) initiation groups. The vasopressor inotropic score (VIS), sequential organ failure assessment (SOFA) score, and lactate clearance before and 24 h post-PMX-DHP were compared. Results: Overall, 52.17% died from multiple organ dysfunction, with a lower mortality rate in the early initiation group. The VIS and SOFA score decreased in both groups, but the magnitude of decrease was not significant. Lactate clearance improved in both groups, with greater improvement in the early initiation group. Univariable analysis identified associations of in-hospital mortality with early initiation, ΔC-reactive protein, lactate clearance, ΔSOFA score, and ΔVIS. Multivariable analysis demonstrated associations of in-hospital mortality risk with ΔSOFA score and early PMX-DHP initiation. Overall survival was higher in the early initiation group. Early initiation of PMX-DHP in patients with cancer with refractory septic shock reduced in-hospital mortality and improved lactate clearance.

Determining genotype–phenotype correlations in patients with hypodontia is important for understanding disease pathogenesis, although only a few studies have elucidated it. We aimed to identify genetic variants linked to non-syndromic bilateral mandibular second premolar hypodontia in a Korean population for the first time by specifying the phenotype of hypodontia. Twenty unrelated individuals with non-syndromic bilateral mandibular second premolar hypodontia were enrolled for whole-exome sequencing. Using a tooth agenesis gene set panel consisting of 112 genes based on literature, potential candidate variants were screened through variant filtering and prioritization. We identified 13 candidate variants in 12 genes, including a stop-gain variant (c.4750C>T) in LAMA3. Through the functional enrichment analysis of the prioritized genes, several terms related to tooth development were enriched in a protein–protein interaction network of candidate genes for mandibular premolar hypodontia. The hypodontia group also had approximately 2-fold as many mutated variants in all four genes related to these key terms, which are CDH1, ITGB4, LAMA3, LAMB3, as those in the 100 healthy control group individuals. The relationship between enriched terms and pathways and mandibular premolar hypodontia was also investigated. In addition, we identified some known oligodontia variants in patients with hypodontia, strengthening the possibility of synergistic effects in other genes. This genetic investigation may be a worthwhile preliminary attempt to reveal the pathogenesis of tooth agenesis and sets a background for future studies.

IntroductionThe analgesia nociception index (ANI) monitor is a nociception monitoring device based on heart rate variability. We aimed to determine the effect of ANI monitor-based intraoperative nociception control on the perioperative stress response during laparoscopic surgery in the Trendelenburg position.MethodsAltogether, 72 female patients who underwent total laparoscopic hysterectomy were randomized to either the control or ANI group. Intraoperative nociception was controlled by remifentanil administration in a conventional manner (based on blood pressure and heart rate) in the control group and by ANI monitoring in the ANI group. Perioperative stress responses were estimated by measuring the levels of serum catecholamines and catabolic stress hormones at three timepoints: after loss of consciousness, at the end of surgery, and 1 h after the end of surgery.ResultsThe serum cortisol level at the end of surgery was significantly higher in the ANI group than in the control group (p

Abstract Ixazomib‐lenalidomide‐dexamethasone (ixazomib‐Rd) showed clinical efficacy over placebo‐Rd in patients with relapsed/refractory multiple myeloma (MM) in the TOURMALINE‐MM1 trial. Over a median follow‐up of ∼85 months, as patients showed disease progression, they received subsequent novel therapies that confounded the overall survival (OS) benefit. Here, we conducted a post hoc analysis in 148 patients from seven countries defined as emerging markets, with limited access to novel therapies for MM during the trial period, to describe the impact of these therapies on OS. Patients were randomised to ixazomib‐Rd (n = 71) or placebo‐Rd (n = 77). The median progression‐free survival (PFS) was 18.7 versus 10.2 months, with ixazomib‐Rd versus placebo‐Rd (hazard ratio [HR], 0.504; p = 0.008) demonstrating a statistically significant improvement as observed in the primary trial. The median OS improved by 32.6 months with ixazomib‐Rd over placebo‐Rd (63.5 vs. 30.9 months; HR, 0.794; p = 0.261); however, the statistically significant benefit seen in PFS was not observed for OS. Improvement with ixazomib‐Rd over placebo‐Rd was observed in overall response (81.7% vs. 64.9%; odds ratio [OR], 2.38; p = 0.019) and complete response (22.5% vs. 3.9%; OR, 7.57; p < 0.001). Patient‐reported quality of life and use of subsequent therapies were similar across treatment groups. No new safety concerns were identified. Compared with the main cohort, median OS was 10 months longer with ixazomib‐Rd and 21 months shorter with placebo‐Rd in this subgroup, indicating a clinically meaningful survival benefit of ixazomib‐Rd treatment in this patient population with limited access to subsequent novel therapies.

Abstract 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

Abstract Background The clinical features of Alzheimer’s disease (AD) vary substantially depending on whether the onset of cognitive deficits is early or late. The amount and distribution patterns of tau pathology are thought to play a key role in the clinical characteristics of AD, which spreads throughout the large-scale brain network. Here, we describe the differences between tau-spreading processes in early- and late-onset symptomatic individuals on the AD spectrum. Methods We divided 74 cognitively unimpaired (CU) and 68 cognitively impaired (CI) patients receiving 18F-flortaucipir positron emission tomography scans into two groups by age and age at onset. Members of each group were arranged in a pseudo-longitudinal order based on baseline tau pathology severity, and potential interregional tau-spreading pathways were defined following the order using longitudinal tau uptake. We detected a multilayer community structure through consecutive tau-spreading networks to identify spatio-temporal changes in the propagation hubs. Results In each group, ordered tau-spreading networks revealed the stage-dependent dynamics of tau propagation, supporting distinct tau accumulation patterns. In the young CU/early-onset CI group, tau appears to spread through a combination of three independent communities with partially overlapped territories, whose specific driving regions were the basal temporal regions, left medial and lateral temporal regions, and left parietal regions. For the old CU/late-onset CI group, however, continuation of major communities occurs in line with the appearance of hub regions in the order of bilateral entorhinal cortices, parahippocampal and fusiform gyri, and lateral temporal regions. Conclusion Longitudinal tau propagation depicts distinct spreading pathways of the early- and late-onset AD spectrum characterized by the specific location and appearance period of several hub regions that dominantly provide tau.

Background/Aims We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Edible insects are promising future food resources globally. Herein, the structural, physicochemical, and bio-functional properties of edible insect protein isolates (EPIs) extracted from Protaetia brevitarsis larvae were investigated. The results showed that EPIs have a high total essential amino acid content; moreover, β-sheet is the major secondary protein structure. The EPI protein solution was highly soluble and electrically stable and did not aggregate easily. In addition, EPIs exhibited immune-enhancing properties; EPI treatment of macrophages induced the activation of macrophages and consequently promoted the production of pro-inflammatory mediators (NO, TNF-α, and IL-1β). Moreover, macrophage activation of EPIs was confirmed to occur through the MAPK and NF-κB pathways. In conclusion, our results suggest that the isolated P. brevitarsis protein can be fully utilized as a functional food material and alternative protein source in the future food industry.

Abstract This work investigates the evolution of the ferroelectric (FE) performance of the sputtered aluminum scandium nitride (AlScN) thin film, which has a high remanent polarization (Pr, > 100 µC cm−2) and coercive field (Ec, > 6 MV cm−1), with the electric field cycling. The work aims at elucidating the underlying origin of the severe fatigue behavior, even with a relatively small number of endurance cycles (

Artemisia argyi (A. argyi) is a medicinal plant belonging to the Asteraceae family and Artemisia genus. Flavonoids abundant in A. argyi are associated with anti-inflammatory, anticancer, and antioxidative effects. Eupatilin and jaceosidin are representative polymethoxy flavonoids with medicinal properties significant enough to warrant the development of drugs using their components. However, the biosynthetic pathways and related genes of these compounds have not been fully explored in A. argyi. This study comprehensively analyzed the transcriptome data and flavonoids contents from four different tissues of A. argyi (young leaves, old leaves, trichomes collected from stems, and stems without trichomes) for the first time. We obtained 41,398 unigenes through the de-novo assembly of transcriptome data and mined promising candidate genes involved in the biosynthesis of eupatilin and jaceosidin using differentially expressed genes, hierarchical clustering, phylogenetic tree, and weighted gene co-expression analysis. Our analysis led to the identification of a total of 7,265 DEGs, among which 153 genes were annotated as flavonoid-related genes. In particular, we were able to identify eight putative flavone-6-hydroxylase (F6H) genes, which were responsible for providing a methyl group acceptor into flavone basic skeleton. Furthermore, five O-methyltransferases (OMTs) gene were identified, which were required for the site-specific O-methylation during the biosynthesis of eupatilin and jaceosidin. Although further validation would be necessary, our findings pave the way for the modification and mass-production of pharmacologically important polymethoxy flavonoids through genetic engineering and synthetic biological approaches.

Ovalbumin (OA) is a major protein in egg white, and enzymatic hydrolysis of OA is well-known to improve its functional properties. In this study, the immune-enhancing effects of OA hydrolysates (OAH), prepared using proteolytic enzymes (Alcalase®, α-chymotrypsin, Flavourzyme®, Neutrase®, and papain) in RAW 264.7 macrophages, were investigated. All the OAH enhanced NO production, with the maximum level found in the OAH prepared with papain (OAPP) by increasing the expression of iNOS mRNA and protein. RAW 264.7 macrophages treated with the OAPP showed higher mRNA expression levels and the production of pro-inflammatory cytokines (TNF-α and IL-6). The evaluation results with specific inhibitors showed that the mitogen-activated protein kinase (MAPK) signaling pathway involved the macrophage activation induced by the OAPP. Moreover, the immunomodulatory activity of OAPP was improved under the in vitro gastrointestinal digestion model, indicating that the OAPP could be used as an effective immune-enhancing agent in the functional food industry.

In this study, we introduce a novel framework that combines human motion parameterization from a single inertial sensor, motion synthesis from these parameters, and biped robot motion control using the synthesized motion. This framework applies advanced deep learning methods to data obtained from an IMU attached to a human subject’s pelvis. This minimalistic sensor setup simplifies the data collection process, overcoming price and complexity challenges related to multi-sensor systems. We employed a Bi-LSTM encoder to estimate key human motion parameters: walking velocity and gait phase from the IMU sensor. This step is followed by a feedforward motion generator-decoder network that accurately produces lower limb joint angles and displacement corresponding to these parameters. Additionally, our method also introduces a Fourier series-based approach to generate these key motion parameters solely from user commands, specifically walking speed and gait period. Hence, the decoder can receive inputs either from the encoder or directly from the Fourier series parameter generator. The output of the decoder network is then utilized as a reference motion for the walking control of a biped robot, employing a constraint-consistent inverse dynamics control algorithm. This framework facilitates biped robot motion planning based on data from either a single inertial sensor or two user commands. The proposed method was validated through robot simulations in the MuJoco physics engine environment. The motion controller achieved an error of ≤5° in tracking the joint angles demonstrating the effectiveness of the proposed framework. This was accomplished using minimal sensor data or few user commands, marking a promising foundation for robotic control and human–robot interaction.

Type A acute aortic syndrome (urgent AAS, UAAS) has a low incidence and high mortality rate; however, it is often missed or diagnosed late. Our aim was to create a new tool for distinguishing UAAS by using multiple modalities to select patients for CT aortography. This study included 75 patients with UAAS, 77 with acute coronary syndrome (ACS), and 81 with heart failure (HF) who received urgent treatment after propensity matching. Specific symptoms, past medical history, mediastinal width, region of interest (ROI) ratio in the lung base/apex, D-dimers, and troponin I were investigated to differentiate UAAS from ACS and HF. The most significant variables were selected to create a new scoring system. The UAAS score exhibited a performance AUC of 0.982. A simple UAAS score >1, excluding ROI ratios in lung base/apex, showed an AUC of 0.977, a sensitivity of 96%, and specificity of 92.41%. The results were validated using an external data set of 292 patients (simple UAAS score > 1: AUC of 0.966, sensitivity 93.33%, and specificity 95.36%). The simple UAAS score may be a valuable tool for suspecting UAAS and may reduce the likelihood of misdiagnosis or performing unnecessary CT aortography.