A Study on the Effects of a Self-Administered Eye Exercise Program on the Balance and Gait Ability of Chronic Stroke Patients: A Randomized Controlled Trial.

This study investigates the effects of a self-administered eye exercise (SEE) program on the balance and gait ability of chronic stroke patients hospitalized due to hemiplegia. This study includes 42 patients diagnosed with stroke-related hemiplegia and hospitalized at D Rehabilitation Hospital. The researcher randomly allocated 42 patients into two groups: the experimental group (EG, n = 21, mean age = 58.14 ± 7.69 years, mean BMI = 22.83 ± 2.19 kg/m2) and the control group (CG, n = 21, mean age = 58.57 ± 6.53 years, mean BMI = 22.81 ± 2.36 kg/m2). The SEE program was applied to the EG and the general self-administered exercise (SE) program was applied to the CG. After 4 weeks of intervention, weight distribution of the affected side, the Timed Up and Go test (TUG), step length of the affected side, step length of the unaffected side, gait speed, and cadence were analyzed and compared. In the within-group comparison, both groups showed significant differences in weight distribution (p < 0.05), TUG (p < 0.05), step length of the affected side (p < 0.05), step length of the unaffected side (p < 0.05), gait speed (p < 0.05), and cadence (p < 0.05). In the between-group comparison, a significant difference in the TUG (p < 0.05) was observed. The SEE program had an overall similar effect to the SE program in improving the balance and gait ability of chronic stroke patients, and had a greater effect on dynamic balance ability. Therefore, the SEE program can be proposed as a self-administered exercise program to improve balance and gait ability in stroke patients who are too weak to perform the SE program in a clinical environment or have a high risk of falling.

Evaluation of exposure to cyanogenic glycosides and potential hydrogen cyanide release in commercially available foods among the Korean population.

The release of hydrogen cyanide (HCN) after food ingestion can pose a serious health risk to consumers. This study aimed to simultaneously quantify four cyanogenic glycosides (lotaustralin, prunasin, taxiphyllin, and dhurrin) using liquid chromatography-tandem mass spectrometry. The analysis scope extended beyond agricultural products to various consumer foods to estimate dietary exposure to cyanogenic glycosides and assess its risk levels. The major exposure sources are cassava chips (lotaustralin), apples (seeds) (prunasin and dhurrin), and Prunus mume axis (taxiphyllin). In addition to quantifying specific cyanogenic glycosides, this study proposed the development of a preliminary risk assessment framework based on the dietary exposure assessment and the calculation of theoretical levels of HCN derived from cyanogenic glycoside concentrations. In the absence of established guidelines for the permissible intake of foods containing cyanogenic glycosides, this study provides initial guidance for assessing the risks associated with a range of commonly consumed foods.

Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting. METHODS: ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m2 for 2 h every 21 days and capecitabine 1000 mg/m2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed. FINDINGS: Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy. INTERPRETATION: The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer. FUNDING: Ono Pharmaceutical and Bristol Myers Squibb.

Risk assessment of cyclohexasiloxane D6 in cosmetic products.

Dodecamethylcyclohexasiloxane (D6) is a siloxane substance mainly used in cosmetics and personal care products. While octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were once commonly used in personal care products, their usage has been restricted due to the classification as persistent, bioaccumulative, and toxic (PBT)/very persistent and very bio-accumulative (vPvB) substances. While D6 has emerged as a substitute for D4 and D5, the risk assessment for D6 remains limited compared to the evaluations for D4 and D5. To address this gap, we conducted a comprehensive risk assessment of D6. In this study, we reviewed the toxicity information on D6 and calculated the exposure level to D6, considering the content of D6 in cosmetic products. No observed adverse effect level (NOAEL) of 1500 mg/kg bw/day was established in a repeated dose toxicity study after oral administration to rats. Negative results were found in tests on the ocular and skin irritation, skin sensitization, and genotoxicity of D6. According to the product content of up to 48% of D6 reported in 2012, the Systemic Exposure Dose (SED) was 5.4E-06 to 7.04 mg/kg bw/day for a 60 kg adult using the exposure factors from Korean cosmetic usage. The Margin of Safety was estimated to be between 35.5 and 4.63E+07, posing a potential health risk of D6 according to the maximum concentration and the product type. Further consideration of the potential of D6 as PBT or vPvB is also required.

Safety assessment of cocamidopropyl betaine, a cosmetic ingredient.

Cocamidopropyl betaine (CAPB) is a surfactant derived from coconut oil that is widely used in cosmetics and personal products for several purposes, such as a surfactant, foam booster, mildness, and viscosity control. Cocamidopropyl betaine is used at concentrations up to 30% in cosmetics. The acute toxicity, skin irritation, eye irritation, skin sensitization, repeated dose toxicity, genotoxicity, carcinogenicity, and phototoxicity of cocamidopropyl betaine were evaluated. Cocamidopropyl betaine was observed to induce mild skin irritation, eye irritation and skin sensitization. The NOAEL of cocamidopropyl betaine was determined to be 250 mg/kg/day based on the results of a 92-day repeated-dose oral toxicity study in rats. The systemic exposure dose of cocamidopropyl betaine was estimated to range from 0.00120 to 0.93195 mg/kg/day when used in cosmetic products. The margin of safety of cocamidopropyl betaine was calculated to be greater than 100 when used at a maximum concentration of 6% in leave-on products and 30% in rinse-off products, suggesting that its use in cosmetic products is safe under current usage conditions.

[IDEN Consensus on Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy].

Antithrombotic agents, including antiplatelet agent and anticoagulants are widely used in Korea due to increasing incidence of cardio-cerebrovascular disease and aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. Clinical practice guideline regarding this issue which was developed by the Korean Society of Gastrointestinal Endoscopy was published in 2020. However, since then, new evidence has emerged for the use of dual antiplatelet therapy and direct anticoagulant management, and revised guidelines were issued in the US and Europe. Accordingly, the previous guidelines were revised, cardiologists also participated in the development group, and the recommendations went through a consensus process among international experts. This guideline presents 14 recommendations made according to the Grading of Recommendations, Assessment, Development, and Evaluation methodology, and was reviewed by multidisciplinary experts. This guideline provides useful information that can assist endoscopists in the management of patients on antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

Development of an In-Pipe Inspection Robot for Large-Diameter Water Pipes.

This paper describes the development of an in-pipe inspection robot system designed for large-diameter water pipes. The robot is equipped with a Magnetic Flux Leakage (MFL) sensor module. The robot system is intended for pipes with diameters ranging from 900 mm to 1200 mm. The structure of the in-pipe inspection robot consists of the front and rear driving parts, with the inspection module located centrally. The robot is powered by 22 motors, including eight wheels with motors positioned at both the bottom and the top for propulsion. To ensure that the robot's center aligns with that of the pipeline during operation, lifting units have been incorporated. The robot is equipped with cameras and LiDAR sensors at the front and rear to monitor the internal environment of the pipeline. Pipeline inspection is conducted using the MFL inspection modules, and the robot's driving mechanism is designed to execute spiral maneuvers while maintaining contact with the pipeline surface during rotation. The in-pipe inspection robot is configured with wireless communication modules and batteries, allowing for wireless operation. Following its development, the inspection robot underwent driving experiments in actual pipelines to validate its performance. The field test bed used for these experiments is approximately 1 km in length. Results from the driving experiments on the field test bed confirmed the robot's ability to navigate various curvatures and obstacles within the pipeline. It is posited that the use of the developed in-pipe inspection robot can reduce economic costs and enhance the safety of inspectors when examining aging pipes.

Species identification and pyrethroid resistance genotyping of recently resurgent Cimex lectularius and Cimex hemipterus in Korea.

The global resurgence of bed bug infestations, exacerbated by increasing international travel, trade, and insecticide resistance, has significantly impacted Korea. This study identified the bed bug species and performed pyrethroid resistance genotyping of recently resurgent bed bugs in Korea. Thirty-one regional bed bug samples were collected from 5 administrative regions: Gyeonggi-do (n=14), Seoul (n=13), Busan (n=2), Jeonllanam-do (n=1), and Chungcheongbuk-do (n=1). The samples underwent morphological and molecular identification. Twenty-four regional samples (77.4%) were identified as the tropical bed bug, Cimex hemipterus, and the remaining 7 regional samples (22.6%) were identified as the common bed bug, Cimex lectularius. The C. hemipterus regional samples carried at least three mutations associated with knockdown resistance (kdr), including 2 super-kdr mutations. The 7 C. lectularius regional samples possessed at least one of the 3 kdr-related mutations associated with pyrethroid resistance. This study confirms that the prevalent bed bug species recently in Korea is C. hemipterus, replacing the previously endemic C. lectularius. Additionally, the rise in bed bug populations with pyrethroid resistance underscores the necessity of introducing alternative insecticides.

Failure Prediction of High-Flow Nasal Cannula at the Conventional Oxygen Therapy Phase in the Emergency Department.

INTRODUCTION: The use of high-flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure has been increasing in the emergency department (ED). However, studies are lacking on the prediction of HFNC failure before therapy initiation in the ED. We investigated whether the existing indices, such as the ratio of pulse oximetry oxygen saturation/fraction of inspired oxygen to respiratory rate (ROX) and ratio of ROX index to heart rate (ROX-HR), can accurately predict HFNC failure at the conventional oxygen therapy phase in the ED. METHODS: This retrospective single-center study included patients treated with HFNC in the ED. The ROX and ROX-HR indices were calculated before initiating HFNC. An estimated fraction of inspired oxygen was used for conventional oxygen therapy. We plotted each index's receiver operating characteristics curve and calculated the area under the curve (AUC) for diagnostic capacity. The optimal cutoff values were assessed using the Youden index. The primary outcome was HFNC failure, defined as intubation in the ED. RESULTS: Among the 97 included patients, 25 (25.8%) failed HFNC therapy in the ED. The ROX and ROX-HR indices measured before initiating HFNC showed AUCs of 0.709 and 0.754, respectively. A ROX index of <5.614 and a ROX-HR index of <6.152 were associated with a high risk of intubation, even after correcting for confounding variables. CONCLUSION: The ROX and ROX-HR indices measured before initiating HFNC provide a relatively fair predictive value of HFNC failure in the ED.

Live-Cell Imaging of MicroRNA Expression via Photoinduced Electron Transfer Controlled by Catalytic Hairpin Assembly.

MicroRNAs (miRNAs) serve as emerging biomarkers for a range of diseases, and their quantitative analysis draws increasing attention. Yet, current invasive methods limit continuous tracking within living cells. To overcome this, a nonenzymatic DNA-based nanoprobe is developed for dynamic, noninvasive miRNA tracking via live-cell imaging. This probe features a unique hairpin DNA structure with five guanines that act as internal quenchers, suppressing fluorescence from an attached fluorophore via photoinduced electron transfer. Target miRNA initiates toehold-mediated strand displacement, restoring, and amplifying the fluorescence signal. Additionally, by introducing a single mismatch to the hairpin DNA, the nanoprobe's sensitivity is significantly enhanced, lowering the detection limit to about 60 pM without compromising specificity. To optimize intracellular delivery for prolonged monitoring, the nanoprobe is encapsulated within multilamellar lipid nanovesicles, fluorescently labeled for dual-wavelength ratiometric analysis. The proposed nanoprobe demonstrates a significant advance in live-cell miRNA detection, promising enhanced in situ analysis for a better understanding of miRNAs' pathophysiological function.

Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1α/Lipin1 axis in an aging-related sarcopenia model.

Sarcopenia burdens the older population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are lacking. The glucocorticoid prednisone remodels muscle metabolism on the basis of frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone administration rescued muscle quality in aged 24-month-old mice to a level comparable to that seen in young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α) and its cofactor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed myocyte-specific Lipin1 as a nonredundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes for the coordinated rescue of energy and mass in sarcopenia.

Lenvatinib plus pembrolizumab for patients with previously treated advanced ovarian cancer: Results from the phase 2 multicohort LEAP-005 study.

OBJECTIVES: The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort. METHODS: Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%-45%) by investigator assessment and 35% (19%-55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%-56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%-93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0-8.5) months and 21.3 (11.7-32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3-4, 77%). One patient died from treatment-related hypovolemic shock. CONCLUSIONS: Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status.

Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Varlitinib and Paclitaxel for EGFR/HER2 Co-Expressing Advanced Gastric Cancer: a Multicenter Phase Ib/II Study (K-MASTER-13).

Purpose: Varlitinib is a pan-human epidermal growth (HER) inhibitor targeting epidermal growth factor receptor (EGFR), HER2, and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (IHC) (≥1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median PFS and overall survival (OS) were 3.3 months and 7.9 months, respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), AST/ALT elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion: A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

The Use of Generative AI for Scientific Literature Searches for Systematic Reviews: ChatGPT and Microsoft Bing AI Performance Evaluation.

Background: A large language model is a type of artificial intelligence (AI) model that opens up great possibilities for health care practice, research, and education, although scholars have emphasized the need to proactively address the issue of unvalidated and inaccurate information regarding its use. One of the best-known large language models is ChatGPT (OpenAI). It is believed to be of great help to medical research, as it facilitates more efficient data set analysis, code generation, and literature review, allowing researchers to focus on experimental design as well as drug discovery and development. Objective: This study aims to explore the potential of ChatGPT as a real-time literature search tool for systematic reviews and clinical decision support systems, to enhance their efficiency and accuracy in health care settings. Methods: The search results of a published systematic review by human experts on the treatment of Peyronie disease were selected as a benchmark, and the literature search formula of the study was applied to ChatGPT and Microsoft Bing AI as a comparison to human researchers. Peyronie disease typically presents with discomfort, curvature, or deformity of the penis in association with palpable plaques and erectile dysfunction. To evaluate the quality of individual studies derived from AI answers, we created a structured rating system based on bibliographic information related to the publications. We classified its answers into 4 grades if the title existed: A, B, C, and F. No grade was given for a fake title or no answer. Results: From ChatGPT, 7 (0.5%) out of 1287 identified studies were directly relevant, whereas Bing AI resulted in 19 (40%) relevant studies out of 48, compared to the human benchmark of 24 studies. In the qualitative evaluation, ChatGPT had 7 grade A, 18 grade B, 167 grade C, and 211 grade F studies, and Bing AI had 19 grade A and 28 grade C studies. Conclusions: This is the first study to compare AI and conventional human systematic review methods as a real-time literature collection tool for evidence-based medicine. The results suggest that the use of ChatGPT as a tool for real-time evidence generation is not yet accurate and feasible. Therefore, researchers should be cautious about using such AI. The limitations of this study using the generative pre-trained transformer model are that the search for research topics was not diverse and that it did not prevent the hallucination of generative AI. However, this study will serve as a standard for future studies by providing an index to verify the reliability and consistency of generative AI from a user's point of view. If the reliability and consistency of AI literature search services are verified, then the use of these technologies will help medical research greatly.

The influence of smoothness and speed of stand-to-sit movement on joint kinematics, kinetics, and muscle activation patterns.

Background: Stand-to-sit (StandTS) is an important daily activity widely used in rehabilitation settings to improve strength, postural stability, and mobility. Modifications in movement smoothness and speed significantly influence the kinematics, kinetics, and muscle activation patterns of the movement. Understanding the impact of StandTS speed and smoothness on movement control can provide valuable insights for designing effective and personalized rehabilitation training programs. Research question: How do the smoothness and speed of StandTS movement affect joint kinematics, kinetics, muscle activation patterns, and postural stability during StandTS? Methods: Twelve healthy younger adults participated in this study. There were two StandTS conditions. In the reference condition, participants stood in an upright position with their feet positioned shoulder-width apart on the force plate. Upon receiving a visual cue, participants performed StandTS at their preferred speed. In the smooth condition, participants were instructed to perform StandTS as smoothly as possible, aiming to minimize contact pressure on the seat. Lower leg kinetics, kinematics, and coordination patterns of muscle activation during StandTS were measured: (1) angular displacement of the trunk, knee, and hip flexion; (2) knee and hip extensor eccentric work; (3) muscle synergy pattern derived from electromyography (EMG) activity of the leg muscles; and (4) postural sway in the anterior-posterior (A-P), medio-lateral (M-L), and vertical directions. Results: Compared to the reference condition, the smooth condition demonstrated greater eccentric knee extensor flexion and increased joint work in both the knee and hip joints. Analysis of specific muscle synergy from EMG activity revealed a significant increase in the relative contribution of hip joint muscles during the smooth condition. Additionally, a negative correlation was observed between knee extensor and vertical postural sway, as well as hip extensor work and M-L postural sway. Conclusion: Smooth StandTS facilitates enhanced knee eccentric control and increased joint work at both the hip and knee joints, along with increased involvement of hip joint muscles to effectively manage falling momentum during StandTS. Furthermore, the increased contributions of knee and hip joint work reduced postural sway in the vertical and M-L directions, respectively. These findings provide valuable insights for the development of targeted StandTS rehabilitation training.

Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.