Ground Force Precision Calibration Method for Customized Piezoresistance Sensing Flexible Force Measurement Mat.

A force plate is mainly used in biomechanics; it aims to measure the ground reaction force in a person's walking or standing position. In this study, a large-area force mat of the piezoresistance sensing type was developed, and a deep-learning-based weight measurement calibration method was applied to solve the problem in which measurements are not normalized because of physical limitations in hardware and signal processing. The test set was composed of the values measured at each point by weight and the value of the center of the pressure variable, and the measured value was predicted using a deep neural network (DNN) regression model. The calibration verification results show that the average weight errors range from a minimum of 0.06% to a maximum of 3.334%. This is simpler than the previous method, which directly measures the ratio of the resistance value to the measured weight of each sensor and derives an equation.

Validation of the 2022 European LeukemiaNet risk stratification for acute myeloid leukemia.

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2). The levels of anti-RBD IgG and neutralizing antibodies increased significantly from baseline through post-dose 1 to post-dose 2 in all three groups. At the post-dose 1, the anti-RBD IgG and neutralizing antibody levels were significantly lower in cancer patients than in healthy controls. However, by post-dose 2, the seropositivity of anti-RBD IgG and neutralizing antibodies uniformly reached 100% across all groups, with no significant disparity in antibody levels among the three groups. Moreover, the antibody titers were not significantly different between patients with a vaccine and chemotherapy interval of more than 14 days or those with less than 14 days. This study demonstrated that after second doses of mRNA COVID-19 vaccines, humoral immune responses in patients receiving chemotherapy were comparable to those of healthy controls, regardless of whether the purpose of the anti-cancer treatment was palliative or adjuvant. Furthermore, the timing of vaccination did not affect the level of humoral immunity after the second vaccination.

Hepatic arterial infusion chemotherapy versus systemic therapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.

Introduction: To investigate the effects of hepatic arterial infusion chemotherapy (HAIC) with or without systemic chemotherapy compared to systemic chemotherapy alone in patients with locally advanced hepatocellular carcinoma (HCC). Methods: Following a registered protocol (PROSPERO 2023 CRD42023386780 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023386780), a comprehensive search was performed using reputable databases and registries up to December 26, 2022, with no language, publication date, or status restrictions. Only randomized controlled trials (RCTs) investigating the effects of HAIC with or without systemic chemotherapy versus systemic therapy alone were included. The primary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events. The secondary outcomes included the objective response rate (ORR) and disease control rate (DCR). A random-effects model was used, and the certainty of the evidence was rated using GRADE. Results: Seven RCTs involving 1,010 patients were included. All trials utilized sorafenib as the comparator. Five trials (690 patients) compared HAIC plus sorafenib to sorafenib alone, while two trials (320 patients) compared HAIC to sorafenib. The results indicate that HAIC, with or without sorafenib, may increase OS, PFS, and ORR compared with sorafenib alone. HAIC may enhance DCR, but the evidence is very uncertain. Adverse events were comparable between HAIC plus sorafenib and sorafenib alone. However, adverse events might be decreased in HAIC alone. Discussion: HAIC with or without systemic chemotherapy may improve survival outcomes and response rates of patients with HCC. Since the current body of evidence is moderate to very low, more robust randomized trials are needed to confirm the efficacy of HAIC. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=386780, identifier CRD42023386780.

Adaptive Control Method for Gait Detection and Classification Devices with Inertial Measurement Unit.

Cueing and feedback training can be effective in maintaining or improving gait in individuals with Parkinson's disease. We previously designed a rehabilitation assist device that can detect and classify a user's gait at only the swing phase of the gait cycle, for the ease of data processing. In this study, we analyzed the impact of various factors in a gait detection algorithm on the gait detection and classification rate (GDCR). We collected acceleration and angular velocity data from 25 participants (1 male and 24 females with an average age of 62 ± 6 years) using our device and analyzed the data using statistical methods. Based on these results, we developed an adaptive GDCR control algorithm using several equations and functions. We tested the algorithm under various virtual exercise scenarios using two control methods, based on acceleration and angular velocity, and found that the acceleration threshold was more effective in controlling the GDCR (average Spearman correlation -0.9996, p < 0.001) than the gyroscopic threshold. Our adaptive control algorithm was more effective in maintaining the target GDCR than the other algorithms (p < 0.001) with an average error of 0.10, while other tested methods showed average errors of 0.16 and 0.28. This algorithm has good scalability and can be adapted for future gait detection and classification applications.

Time-efficient implantable catheters for draining malignant ascites in terminal cancer patients.

BACKGROUND: There is a need for an improved version of the implantable catheter for malignant ascites in the abdominal cavity. OBJECTIVE: New implantable catheters have been developed that drain ascites from the abdominal cavity to the bladder by applying pressure. Based on pigtail catheters, these newly designed catheters have silicone membranes and apertures. METHODS: Experimental instruments controlled flow rates and water level to observe changes of the activation pressure and its cycle time along flow rates and turns of catheters. Furthermore, various normality tests, difference tests and non-parametric tests were investigated to observe statistical validity. RESULTS: Cycle times were significantly affected by flow rate (3/4 cases of p< 0.05). The effects of flow rate on activation pressure, however, were not significant (1/4 case of p< 0.05). Cycle times were not significantly affected by the number of turns of the catheter (3/8 cases of p< 0.05). In contrast, the effects of the turns on activation pressure were significant (5/8 cases of p< 0.05). CONCLUSION: Overall, there was no significant difference between cycle times for 1.5 turns and 2.0 turns of catheters. In addition, catheters with 1.5 turns have a lower activation pressure than catheters with 2.0 turns. It is possible to customize catheters based on the ascites excretion and urination rates of various terminal patients.

A Phase I Study of Locoregional High-Dose Autologous Natural Killer Cell Therapy With Hepatic Arterial Infusion Chemotherapy in Patients With Locally Advanced Hepatocellular Carcinoma.

Background: To explore the feasibility and safety of natural killer (NK) cell therapy in HCC, we performed a prospective, open-label, phase I trial to evaluate the synergistic effect of locoregional high-dose autologous NK cell therapy in combination with hepatic arterial infusion chemotherapy (HAIC). Methods: Patients with locally advanced HCC who were refractory to the standard treatment were eligible for this study. Patients received expanded and activated NK cells for 5 consecutive days in a dose-escalating manner (dose 2.5×108, 5×108, 10×108 NK cells/injection) through hepatic arterial infusion following 4 cycles of HAIC with 5-fluorouracil (750 mg/m2) and cisplatin (25 mg/m2). The primary endpoint was the safety of NK cell-based immunotherapy, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immunologic responses. Results: Of the 11 patients enrolled, the confirmed ORR was 63.6% (complete response [CR]: 36.4%, confirmed partial response [PR]: 27.3%). Stable disease (SD) and progressive disease (PD) were observed in two patients (18.2%) each, resulting in a disease control rate (DCR) of 81.8%. The median PFS and OS were 10.3 and 41.6 months, respectively. There were no incidences of decompensation or severe adverse events during HAIC, and no adverse events related to NK cell infusion were noted. Conclusion: The combination of HAIC and locoregional high-dose NK cell therapy is a safe and effective treatment for locally advanced HCC patients who were refractory to the standard treatment. This result warrants further development of this novel treatment to establish its efficacy in HCC. Clinical Trial Registration: cris.nih.go.kr, identifier KCT0003973.

Prognostic Significance of the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Neuroendocrine Carcinoma.

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.

Gait Disorder Detection and Classification Method Using Inertia Measurement Unit for Augmented Feedback Training in Wearable Devices.

Parkinson's disease (PD) is a common neurodegenerative disease, one of the symptoms of which is a gait disorder, which decreases gait speed and cadence. Recently, augmented feedback training has been considered to achieve effective physical rehabilitation. Therefore, we have devised a numerical modeling process and algorithm for gait detection and classification (GDC) that actively utilizes augmented feedback training. The numerical model converted each joint angle into a magnitude of acceleration (MoA) and a Z-axis angular velocity (ZAV) parameter. Subsequently, we confirmed the validity of both the GDC numerical modeling and algorithm. As a result, a higher gait detection and classification rate (GDCR) could be observed at a higher gait speed and lower acceleration threshold (AT) and gyroscopic threshold (GT). However, the pattern of the GDCR was ambiguous if the patient was affected by a gait disorder compared to a normal user. To utilize the relationships between the GDCR, AT, GT, and gait speed, we controlled the GDCR by using AT and GT as inputs, which we found to be a reasonable methodology. Moreover, the GDC algorithm could distinguish between normal people and people who suffered from gait disorders. Consequently, the GDC method could be used for rehabilitation and gait evaluation.

Observational Study of Peritoneal Washing Cytology-Positive Gastric Cancer without Gross Peritoneal Metastasis in Patients who Underwent Radical D2 Gastrectomy.

Background The clinical features and therapeutic strategies for gastric cancer with positive peritoneal washing cytology but without visible gross peritoneal metastasis have not been defined. The aim of this study was to evaluate the effect and clinical prognostic value of postoperative chemotherapy in gastric cancer patients with positive peritoneal washing cytology without gross peritoneal metastasis who underwent radical D2 gastrectomy in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods Intraoperative peritoneal washing cytology was performed in 285 patients who underwent radical D2 gastrectomy between April 2004 and May 2016. Of them, 88 patients with positive cytology but without gross peritoneal metastasis were included in the study. In total, 64 patients received postoperative chemotherapy, whereas 24 patients underwent surgery only. Results Most gastric cancer patients with positive cytology without gross peritoneal metastasis demonstrated pT4 and/or pN3 disease. Postoperative chemotherapy improved DFS and OS compared to surgery only in gastric cancer patients with positive cytology without gross peritoneal metastasis (median DFS 11.63 vs. 6.98 months, p < 0.001; median OS 25.50 vs. 12.11 months, p < 0.001). In multivariate analyses of gastric cancer patients with positive cytology without gross peritoneal metastasis, no chemotherapy was the strongest clinical factor for poorer DFS (hazard ratio [HR] 3.76, p < 0.001) or OS (HR 4.37, p < 0.001). Conclusion Postoperative chemotherapy improves the survival outcome compared to surgery alone in gastric cancer patients with positive peritoneal washing cytology but without visible gross peritoneal metastasis who underwent radical D2 gastrectomy.

Cisplatin-induced Atrioventricular Block Requiring a Pacemaker: Two Case Reports and a Literature Review.

Chemotherapeutic drugs can cause cardiac toxicities such as cardiomyopathy, arrhythmia, and cardiovascular disease. The well-known side effects of cisplatin are nephrotoxicity, nausea, vomiting, and electrolyte imbalance. Cardiotoxicity induced by cisplatin is rare, and its pathophysiology is unknown. Here, we present two cases of complete and high-degree atrioventricular (AV) block that occurred during cisplatin-based chemotherapy and required pacemaker placement. A 64-year-old woman and a 75-year-old man, who had no underlying heart disease, developed dyspnea without chest pain and bradycardia during cisplatin-based chemotherapy. However, there were no significant differences in their serum electrolyte levels, cardiac enzyme levels, and echocardiography results before and after drug administration. The ECGs were confirmed with complete AV block and high-degree AV block, which requiring pacemaker placement. We assume that cisplatin directly caused the complete, high-degree AV block, which required a pacemaker placement in our cases. In such cases, a cumulative dose of cisplatin over 240 mg/m2 is a risk factor for early symptoms of AV block. If patients complain of dyspnea without chest pain during cisplatin-based chemotherapy, arrhythmic complications should be considered. This information may be helpful for clinicians treating patients with cisplatin chemotherapy.

Lymph-node ratio is an important clinical determinant for selecting the appropriate adjuvant chemotherapy regimen for curative D2-resected gastric cancer.

PURPOSE: Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer. METHODS: We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, > 0.1-0.25; and LNR 3, > 0.25), and their disease-free survival (DFS) was evaluated. RESULTS: The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR > 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P < 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR > 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011). CONCLUSIONS: The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.

HDAC2/3 binding and deacetylation of BubR1 initiates spindle assembly checkpoint silencing.

BubR1 acetylation is essential in spindle assembly checkpoint (SAC) signaling. Here we show that BubR1 deacetylation is a signal that initiates mitotic exit. Sustained BubR1 acetylation arrests the cells in metaphase, although chromosome congression is achieved. BubR1 deacetylation was coordinated with dephosphorylation in mitotic exit, suggesting the presence of a coordinated acetylation-phosphorylation code in mitotic signaling. Histone deacetylase (HDAC) 2 and 3 bound to acetylated BubR1 exclusively in mitosis and led to the polyubiquitination of BubR1. Subsequent degradation of BubR1 resulted in the disassembly of the mitotic checkpoint complex. Importantly, BRCA2 was required for HDAC2/3 association with acetylated BubR1 in nocodazole (Noc)-arrested cells. Plk1, PP2A, P300/CBP-associated factor (PCAF) and BubR1 were found in the mitotic BRCA2 complex, suggesting that BRCA2 acts as a signaling scaffold for BubR1 modification. Furthermore, we show that Plk1 is required for BRCA2 to localize at the prometaphase kinetochore (KT). Inhibition of Plk1 resulted in the loss of BRCA2 from the KT, and so did PCAF, consistent with the loss of BubR1 acetylation. Concordantly, BRCA2-dysfunctional cells exhibited resistance to trichostatin A, which was restored when BRCA2 was introduced. That loss of Brca2 conferred resistance to various HDAC inhibitors was corroborated by the experiments in mouse pancreatic organoids. These results suggest that the BRCA2-BubR1 acetylation-deacetylation pathway is an important decision-making point for the HDAC inhibitor response. Taken together, BRCA2 is a signaling platform for BubR1, and BubR1 deacetylation is a cue for SAC silencing.