Search

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

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.

Not available.

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 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.

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

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.

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.

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.

This study evaluates the capability of a single inertial sensor based joint angles estimation during four different walking patterns in an outdoor setting. The sensor was placed on the upper part of the tibia, which was chosen due to its large range of motion and minimal foot-ground impact. A Bi-LSTM (bidirectional long short-term memory) data-driven approach was used for joint angle estimation. The results showed smaller errors in intra-subject angle estimation compared to inter-subject, with an average MAE (mean absolute error) of 2.11° to 3.65°. The study suggests that deep learning approaches can effectively process data from a single IMU (inertial measurement unit) for accurate human motion monitoring, reducing the need for multiple sensors. Despite using only one sensor and four different walking patterns (zigzag, sideways, backward, and ramp walking), our method achieved similar results to previous studies that used single-motion activities. This study, conducted outdoors without instructing participants, is a step closer to real-world application, potentially providing insights into lower body biomechanics in physiotherapy, mobility improvement progress after surgery, and aiding in the development of personalized exoskeletons robots.

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.

A transfer function is the main model of a design program that correlates mechanistically calculated damage to a pavement with the actual field distress. In this study, a pavement condition index (PCI) model that reflects environmental and traffic loads was developed as a transfer function for a design program for airport concrete pavements. Seven runways from five airports in Korea, for which design data were available, were selected as target runways, and their design, traffic, and weather data were collected. The minimum tensile stress of the slab generated by environmental loads and the maximum tensile stress induced by combined environmental and traffic loads were calculated by conducting a three-dimensional finite element analysis. The cumulative fatigue damage to the target runways was calculated by substituting the climatic conditions and traffic volume into the fatigue model, which considered the minimum and maximum tensile stresses. The PCI, which was uniformly and varyingly distributed according to pavement age, was adopted as the indicator of actual field distress, whereas the previously used structural condition index was mostly 100 because no structural distress occurred, regardless of the pavement age. The PCI model was established via multi-regression analysis to predict field PCIs using mechanistically calculated cumulative fatigue damage and pavement age as independent variables. The actual and predicted PCIs of the target airports were compared to validate the PCI model.

Coronavirus disease 2019 (COVID-19) can lead to acute organ dysfunction, and delirium is associated with long-term cognitive impairment and a prolonged hospital stay. This retrospective single-center study aimed to investigate the risk factors for delirium in patients with COVID-19 infection receiving treatment in an intensive care unit (ICU). A total of 111 patients aged >18 years with COVID-19 pneumonia who required oxygen therapy from February 2021 to April 2022 were included. Data on patient demographics, past medical history, disease severity, delirium, and treatment strategies during hospitalization were obtained from electronic health records. Patient characteristics and risk factors for delirium were analyzed. Old age (P < 0.001), hypertension (P < 0.001), disease severity (Sequential Organ Failure Assessment score) (P < 0.001), mechanical ventilator support (P < 0.001), neuromuscular blocker use (P < 0.001), and length of stay in the ICU (P < 0.001) showed statistically significant differences on the univariable analysis. Multivariable analysis with backward selection revealed that old age (odds ratio, 1.149; 95% confidence interval, 1.037-1.273; P = 0.008), hypertension (odds ratio, 8.651; 95% confidence interval, 1.322-56.163; P = 0.024), mechanical ventilator support (odds ratio, 226.215; 95% confidence interval, 15.780-3243.330; P < 0.001), and length of stay in the ICU (odds ratio, 30.295; 95% confidence interval, 2.539-361.406; P = 0.007) were significant risk factors for delirium. In conclusion, old age, ICU stay, hypertension, mechanical ventilator support, and neuromuscular blocker use were predictive factors for delirium in COVID-19 patients in the ICU. The study findings suggest the need for predicting the occurrence of delirium in advance and preventing and treating delirium.

Coronavirus disease 2019 (COVID-19) is associated with a systemic inflammatory response that activates coagulation in symptomatic patients. In addition, a rare form of thrombosis has been reported in people who received the COVID-19 vaccine, most of whom were women younger than 50 years of age. Considering that hormonal contraceptive methods widely used by women of childbearing age increase the risk of thrombosis, the development of guidelines for the use of hormonal contraceptives in the era of the COVID-19 pandemic is necessary. In this context, the Korean Society of Contraception and Reproductive Health provides guidelines for issues regarding contraception and reproductive health during the pandemic.

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results : (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions: The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Purpose Intraoperative cardiac arrest (IOCA) is rare, unpredictable, and may result in a poor outcome. The features of IOCA during cancer surgery and factors related to survival following an IOCA were examined. Methods This was a retrospective study of patients who had cancer surgery under general anesthesia between March 2009 and March 2021 (n = 84,615) to determine the number of patients who had an IOCA. Patients’ clinical information, cause of IOCA, hypoxemia during anesthesia, and the duration of hypotension and CPR were analyzed. Results A total of 22 cases of IOCA occurred during cancer surgery (overall incidence: 2.6 per 10,000 surgeries). Return of spontaneous circulation was achieved in 17 patients, but only 13 survived until discharge. There were statistically significant differences between the deceased and the survival cancer patient groups in; (1) duration of hypoxemia (survival group: 5 minutes, range: 2–18 minutes; deceased group: 60 minutes, range, 22.5–120 minutes; p = 0.019); (2) duration of hypotension (survival group: 35 minutes, range, 15–55 minutes; deceased group 160 minutes, range, 140–185 minutes; p = 0.007); and (3) total duration of CPR (survival group: 3 minutes, range: 1–15 minutes; deceased group: 40 minutes, range: 19–149 minutes; p = 0.005). Conclusion The duration of hypoxemia and hypotension prior to the onset of IOCA, as well as the duration of CPR were associated with the prognosis of IOCA, highlighting the need to reduce multi-organ damage caused by hypoxemia and hypotension during surgery in high-risk patients.

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator’s choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.

This study investigated the immunostimulatory effect of egg yolk-derived phosvitin phosphopeptides (PPPs) prepared by high-temperature and mild-pressure (HTMP) pretreatment and enzyme combinations in RAW 264.7 macrophages. Treating RAW 264.7 macrophages with PPPs, especially those produced by HTMP pretreatment and trypsin + Multifect 14L combination (HTMP-TM), significantly increased nitric oxide (NO) production. The PPPs increased NO production by inducing the expression of inducible nitric oxide synthase (iNOS) mRNA in RAW 264.7 cells. The mRNA expression and secretion of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-6) were also enhanced by PPPs. Furthermore, PPPs activated the mitogen-activated protein kinase (MAPK) signaling pathway, and PPPs-induced NO production was suppressed by MAPK inhibitors and anti-Toll-like receptor 2 (TLR2) antibody in RAW 264.7 cells. In conclusion, the immunostimulatory effects of PPPs on RAW 264.7 cells were due to the activation of TLR2-mediated MAPK signaling pathway.

Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDAC. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval : 30.9-61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were two CR and five partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AE) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥3 AE emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AE were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat could be a new therapeutic option in patients with R/R PTCL (clinicaltrials gov. Identifier: NCT02953652).

Primary hepatic mixed germ cell tumor (GCT) is very rare, and less than 10 cases have been reported. We report a case of mixed GCT composed of a choriocarcinoma and yolk sac tumor, which occurred in the liver of a 40-year-old woman. A large mass was detected by computed tomography solely in the liver. Serum β-human chorionic gonadotropin (hCG) was highly elevated, otherwise, other serum tumor markers were slightly elevated or within normal limits. For hepatic choriocarcinoma, neoadjuvant chemotherapy was administered, followed by right lobectomy. Histologic features of the resected tumor revealed characteristic choriocarcinoma features with diffuse positivity for hCG in the syncytiotrophoblasts and diffuse positivity for α-fetoprotein and Sal-like protein 4 in the yolk sac tumor components. Primary malignant GCT in the liver is associated with a poor prognosis and requires specific treatment. Therefore, GCT should be considered during a differential diagnosis of a rapidly growing mass in the liver.

Ovotransferrin (OTF), an egg protein known as transferrin family protein, possess strong antimicrobial and antioxidant activity. This is because OTF has two iron binding sites, so it has a strong metal chelating ability. The present study aimed to evaluate the improved immune-enhancing activities of OTF hydrolysates produced using bromelain, pancreatin, and papain. The effects of OTF hydrolysates on the production and secretion of pro-inflammatory mediators in RAW 264.7 macrophages were confirmed. The production of nitric oxide (NO) was evaluated using Griess reagent and the expression of inducible nitric oxide synthase (iNOS) were evaluated using quantitative real-time polymerase chain reaction (PCR). And the production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6) and the phagocytic activity of macrophages were evaluated using an ELISA assay and neutral red uptake assay, respectively. All OTF hydrolysates enhanced NO production by increasing iNOS mRNA expression. Treating RAW 264.7 macrophages with OTF hydrolysates increased the production of pro-inflammatory cytokines and the phagocytic activity. The production of NO and pro-inflammatory cytokines induced by OTF hydrolysates was inhibited by the addition of specific mitogen-activated protein kinase (MAPK) inhibitors. In conclusion, results indicated that all OTF hydrolysates activated RAW 264.7 macrophages by activating MAPK signaling pathway.

Abstract This study aimed to investigate the efficacy of the combination of neuron-specific enolase (NSE) measurement and initial neurological examination in predicting the neurological outcomes of patients with cardiac arrest (CA) by retrospectively analyzing data from the Korean Hypothermia Network prospective registry. NSE levels were recorded at 48 and 72 h after CA. The initial Full Outline of UnResponsiveness (FOUR) and Glasgow Coma Scale (GCS) scores were recorded. These variables were categorized using the scorecard method. The primary endpoint was poor neurological outcomes at 6 months. Of the 475 patients, 171 (36%) had good neurological outcomes at 6 months. The areas under the curve (AUCs) of the categorized NSE levels at 72 h, GCS score, and FOUR score were 0.889, 0.722, and 0.779, respectively. The AUCs of the combinations of categorized NSE levels at 72 h with categorized GCS scores and FOUR score were 0.910 and 0.912, respectively. Each combination was significantly higher than the AUC value of the categorized NSE level at 72 h alone (with GCS: p = 0.015; with FOUR: p = 0.026). Combining NSE measurement and initial neurological examination improved the prediction of neurological outcomes.

Background and Objectives The olfactory fossa is an important anatomical structure to prevent surgical complications such as skull base injury and meningitis. The purpose of this study is to determine if there is a difference in lateral lamella length (LLL) between the left and right sides, a topic that has been studied rarely in Korea. Subjects and Method We analyzed 592 left and right sides of 296 PNS CTs. We measured LLL as the distance between the fovea ethmoidalis and the horizontal cribriform plate in the olfactory fossa of the coronal surface where the crista galli was observed. Results The average LLL on the left side was significantly longer than that on the right. Age and LLL showed a negative correlation. Multiple regression analysis revealed younger age and left side as independent variables for predicting increasing LLL. Conclusion There was a significant difference between the two sides of LLL on sinus CT in Koreans. Before sinus surgery, the asymmetry of the ethmoid roof must be assessed, even by skilled doctors. If the height of the ethmoid roof is asymmetric, extra care is required during sinus surgery.

Objectives: Formononetin is one of the phytoestrogens that functions like a selective estrogen receptor modulator (SERM). In this study, we evaluated the effects of formononetin on endometriosis progression in vitro and in vivo. Materials and methods: After pathological confirmation, 10 eutopic and ectopic endometria were collected from patients with endometriosis. Ten eutopic endometria samples were collected from patients who did not have endometriosis. To determine the cytotoxic dose and therapeutic dose of formononetin, the concentration of 70% of the cells that survived after formononetin administration was estimated using a Cell counting kit-8 (CCK 8) assay. Western blot analysis was used to determine the relative expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 in the eutopic endometria without endometriosis, eutopic endometria with endometriosis, and ectopic endometria with endometriosis as the formononetin concentration was increased. We confirmed the effect of formononetin on apoptosis and migration in endometriosis using fluorescence-activated cell sorting (FACS) and wound healing assays, respectively. A mouse model of endometriosis was prepared using a non-surgical method, as previously described. The mice were intraperitoneally administered formononetin for four weeks after dividing them into control, low-dose formononetin (40 mg/kg/day) treatment, and high-dose (80 mg/kg/day) formononetin treatment groups. All the mice were euthanized after formononetin treatment. Endometriotic lesions were retrieved and confirmed using hematoxylin and eosin (H&E) staining. Immunohistochemical (IHC) staining of p27 was performed. Results: We set the maximum concentration of formononetin administration to 80 μM through the CCK8 assay. Based on formononetin concentration, the expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 proteins were measured using Western blot analysis (N = 4 per group). The expression level of pERK, p27, and pSTAT3 in eutopic endometrium with endometriosis tended to decrease with increasing formononetin concentration, and a significant decrease was noted at 80 μM. The expression of p27 in ectopic endometrium with endometriosis was also significantly decreased at 80 μM of formononetin. FACS analysis revealed that formononetin did not significantly affect apoptosis. In the wound healing assay, formononetin treatment revealed a more significant decrease in the proliferation of the eutopic endometrium in patients with endometriosis than in the eutopic endometrium without endometriosis. Relative expression of sex hormone receptors decreased with increasing formononetin doses. Although no significant differences were observed in the ER, PR-A, ERβ/ERα, and PR-B/PR-A, significant down-regulation of PR-B expression was noted after formononetin treatment at 80 μM. In the in vivo study, endometriotic lesions in the formononetin-treated group significantly decreased compared to those in the control group. The relative expression of p27 using IHC was highest in the control group and lowest in the high-dose formononetin treatment group. Conclusions: Formononetin treatment was shown to inhibit the proliferation of eutopic and ectopic endometria in patients with endometriosis through the regulation of p27, pSTAT3, and PR-B. In an endometriosis mouse model, formononetin treatment significantly reduced the number of endometriotic lesions with decreased p27 expression. The results of this study suggest that formononetin may be used as a non-hormonal treatment option for endometriosis.

Gait analysis is important in a variety of applications such as animation, healthcare, and virtual reality. So far, high-cost experimental setups employing special cameras, markers, and multiple wearable sensors have been used for indoor human pose-tracking and gait-analysis purposes. Since locomotive activities such as walking are rhythmic and exhibit a kinematically constrained motion, fewer wearable sensors can be employed for gait and pose analysis. One of the core parts of gait analysis and pose-tracking is lower-limb-joint angle estimation. Therefore, this study proposes a neural network-based lower-limb-joint angle-estimation method from a single inertial sensor unit. As proof of concept, four different neural-network models were investigated, including bidirectional long short-term memory (BLSTM), convolutional neural network, wavelet neural network, and unidirectional LSTM. Not only could the selected network affect the estimation results, but also the sensor placement. Hence, the waist, thigh, shank, and foot were selected as candidate inertial sensor positions. From these inertial sensors, two sets of lower-limb-joint angles were estimated. One set contains only four sagittal-plane leg-joint angles, while the second includes six sagittal-plane leg-joint angles and two coronal-plane leg-joint angles. After the assessment of different combinations of networks and datasets, the BLSTM network with either shank or thigh inertial datasets performed well for both joint-angle sets. Hence, the shank and thigh parts are the better candidates for a single inertial sensor-based leg-joint estimation. Consequently, a mean absolute error (MAE) of 3.65° and 5.32° for the four-joint-angle set and the eight-joint-angle set were obtained, respectively. Additionally, the actual leg motion was compared to a computer-generated simulation of the predicted leg joints, which proved the possibility of estimating leg-joint angles during walking with a single inertial sensor unit.

Abstract Background Recent experimental studies using herbal extracts have shown the possibility of peripheral nerve regeneration. This study aimed to investigate the effects of herbal extracts on peripheral nerve regeneration in a rat sciatic nerve injury model. Methods A total of 53 rats were randomly assigned to a control group or one of four experimental groups. In all rats, the sciatic nerve was completely severed and microscopic epineural end-to-end neurorrhaphy was performed. Normal saline (2 mL) was topically applied to the site of nerve repair in the control group, whereas four different herbal extracts – 2 mL each of Astragalus mongholicus Bunge, Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, or Paeonia lactiflora Pall. – were topically applied to the site of nerve repair in each experimental group. Nerve conduction studies were performed at an average of 11.9 weeks after the operation, and conduction velocity and proximal and distal amplitudes were measured. Biopsies were performed at an average of 13.2 weeks after the initial neurorrhaphy. The quality of nerve anastomosis and perineural adhesion to the surrounding soft tissues was macroscopically evaluated. The neuroma size at the site of the neurorrhaphy was microscopically measured, whereas the size of the scar tissue was evaluated relative to the diameter of the repaired nerve. Results The nerve conduction study results showed the highest nerve conduction velocity in the experimental group that used the Coptis japonica (Thunb.) Makino extract and the highest proximal and distal amplitudes in the experimental group that used the Aconitum carmichaelii Debeaux extract. Macroscopic evaluations after the second operation showed that grade 2 perineural adhesion was found in 70.8% of rats. The mean neuroma size in the Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, and Paeonia lactiflora Pall. groups showed statistically significant decreases relative to the control group. The mean scar tissue formation index in the Paeonia lactiflora Pall. group showed a statistically significant decrease relative to the control group. Conclusions The peripheral nerve regeneration effect of the herbal extracts was confirmed through decreased neuroma and scar tissue formation.