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Purpose: To evaluate the potential of incorporating respiratory muscle strength, specifically maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP), along with traditional sarcopenia screening measures such as hand grip strength (HGS) and skeletal muscle mass index (SMI), to identify sarcopenia in older men. Materials and Methods: A retrospective analysis was conducted involving male patients aged 65 years and older who underwent measurements of respiratory muscle strength, HGS, and muscle mass at a general hospital in Korea from July 2016 to May 2022. Statistical analysis utilized independent t-tests and receiver operating characteristic (ROC) curves to assess the sensitivity and specificity of MIP, MEP, HGS, and SMI in sarcopenia screening. The cut-off values for sarcopenia screening were determined based on the area under the ROC curve (AUC). Results: The analysis of 282 study participants revealed the following cut-off values for sarcopenia based on the AUC: for MIP, the cut-off value was 65.50 cmH2O (AUC=0.70, sensitivity: 0.63, specificity: 0.61), while for MEP, it was 84.50 cmH2O (AUC=0.74, sensitivity: 0.66, specificity: 0.68). Conclusions: This study showed the utility of respiratory muscle strength in screening for sarcopenia among older men. We suggest the screening cut-off values as 65.50 cmH2O for MIP and 84.50 cmH2O for MEP. Even when HGS and SMI measurements are not feasible, sarcopenia can be reasonably predicted based on respiratory muscle strength.

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa.Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy.Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively.Conclusions: Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.

Abstract Neutrophils perform essential functions in antimicrobial defense and tissue maintenance at mucosal barriers. However, a dysregulated neutrophil response and, in particular, the excessive release of neutrophil extracellular traps (NETs) are implicated in the pathology of various diseases. In this review, we provide an overview of the basic concepts related to neutrophil functions, including NET formation, and discuss the mechanisms associated with NET activation and function in the context of the prevalent oral disease periodontitis.

Abstract Background The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months. Methods In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered. Results At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase. Conclusion A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period. Trial registration The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.

The sit-to-stand test is an essential tool used to assess lower limb function and muscle strength in older adults and various patient populations, and also plays a role in sarcopenia screening. Among its forms, the five-time sit-to-stand test (FTSST) is widely used, with previous studies suggesting cutoff values of >10 seconds and >11 seconds for the sitting-to-standing and standing-to-sitting transitions, respectively. The 30-second and 1-minute sit-to-stand tests (30STS and 1MSTS, respectively) also provide comprehensive assessments. While much of the current research on sarcopenia focuses on the FTSST, there is a burgeoning need for an in-depth exploration of the 30STS and 1MSTS. Studies on these tests are vital to refine the criteria for sarcopenia, establish accurate cutoff values, and enhance diagnostic precision and treatment effectiveness. This need highlights the importance of further research into the 30STS and 1MSTS for refining the diagnostic criteria for sarcopenia.

Abstract HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1–5% of CD4+ T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4’s functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr’s C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr’s capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4+ T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.

Abstract The purpose of this study was to demonstrate the performance of a fully automated, deep learning-based brain segmentation (DLS) method in healthy controls and in patients with neurodevelopmental disorders, SCN1A mutation, under eleven. The whole, cortical, and subcortical volumes of previously enrolled 21 participants, under 11 years of age, with a SCN1A mutation, and 42 healthy controls, were obtained using a DLS method, and compared to volumes measured by Freesurfer with manual correction. Additionally, the volumes which were calculated with the DLS method between the patients and the control group. The volumes of total brain gray and white matter using DLS method were consistent with that volume which were measured by Freesurfer with manual correction in healthy controls. Among 68 cortical parcellated volume analysis, the volumes of only 7 areas measured by DLS methods were significantly different from that measured by Freesurfer with manual correction, and the differences decreased with increasing age in the subgroup analysis. The subcortical volume measured by the DLS method was relatively smaller than that of the Freesurfer volume analysis. Further, the DLS method could perfectly detect the reduced volume identified by the Freesurfer software and manual correction in patients with SCN1A mutations, compared with healthy controls. In a pediatric population, this new, fully automated DLS method is compatible with the classic, volumetric analysis with Freesurfer software and manual correction, and it can also well detect brain morphological changes in children with a neurodevelopmental disorder.

Abstract Background Bone‐subtraction computed tomography angiography (CTA) (BSCTA) is a new technique designed to overcome the limitation of three‐dimensional CTA, where the vessels surrounded by bone and calcification can be obscured. An optimal contrast CT protocol for intracranial artery visualization with BSCTA has yet to be established in dogs. Objectives The purpose of this study was to determine the optimal contrast protocol of CTA for visualizing intracranial artery using an automatic bone‐subtraction technique in dogs. Methods Brain CTA was performed four times for each of nine healthy beagle dogs to cover all the contrast protocols: two different contrast iodine concentrations (300 and 370 mgI/mL) and two different contrast media injection rates (2 and 4 mL/s). Bone removal post‐processing was performed automatically by subtracting the non‐enhanced CT data from the contrast CT data using a dedicated workstation. The bone‐subtracted intracranial vessels were analysed for quantitative and qualitative evaluation. Results Quantitative evaluation showed significantly higher CT attenuation values for the group with a 370 mgI/mL iodine content at a rate of 4 mL/s than the two groups with a 300 mgI/mL iodine content at the rates of 2 and 4 mL/s (p

Radiation therapy is a crucial cancer treatment, but it can damage healthy tissues, leading to side effects like skin injuries and molecular alterations. This study aimed to elucidate histological and molecular changes in canine skin post-radiation therapy (post-RT) over nine weeks, focusing on inflammation, stem cell activity, angiogenesis, keratinocyte regeneration, and apoptosis. Four male beagles received a cumulative radiation dose of 48 Gy, followed by clinical observations, histological examinations, and an RT-qPCR analysis of skin biopsies. Histological changes correlated with clinical recovery from inflammation. A post-RT analysis revealed a notable decrease in the mRNA levels of Oct4, Sox2, and Nanog from weeks 1 to 9. VEGF 188 levels initially saw a slight increase at week 1, but they had significantly declined by week 9. Both mRNA and protein levels of COX–2 and Keratin 10 significantly decreased over the 9 weeks following RT, although COX–2 expression surged in the first 2 weeks, and Keratin 10 levels increased at weeks 4 to 5 compared to normal skin. Apoptosis peaked at 2 weeks and diminished, nearing normal by 9 weeks. These findings offer insights into the mechanisms of radiation-induced skin injury and provide guidance for managing side effects in canine radiation therapy.

Vepdegestrant (formerly ARV-471), a novel proteolysis-targeting chimera (PROTAC), targets estrogen receptor alpha (ERα) for degradation, offering a promising option to treat advanced ER-positive breast cancer. We developed and validated a sensitive and rapid liquid chromatography–tandem mass spectrometry method to quantify vepdegestrant in rodent plasma using bavdegalutamide (formerly ARV-110) as an internal standard. Plasma samples were prepared with protein precipitation using acetonitrile and analyzed using reverse-phase C18 columns and a mobile phase of 10 mM ammonium formate in distilled water and acetonitrile. The method demonstrated linearity from 1 to 1000 ng/mL in mouse and rat plasma, meeting all validation criteria, and successfully applied to in vivo and in vitro studies. Pharmacokinetic analysis revealed low-to-moderate clearance (313.3, 1053 mL/h/kg) and oral bioavailability (17.91, 24.12%) of vepdegestrant in mice and rats, respectively. It was unstable in buffer solutions across pH 2–10 and in phosphate-buffered saline (pH 7.4), likely due to adsorption, but remained stable in mouse and rat plasma at varying temperatures. In liver microsomes, vepdegestrant exhibited moderate stability in rats but was stable in mice, dogs, and humans. These findings enhance the understanding of pharmacokinetic properties of vepdegestrant supporting further development of PROTAC drugs.

Abstract High‐capacity silicon (Si) materials hold a position at the forefront of advanced lithium‐ion batteries. The inherent potential offers considerable advantages for substantially increasing the energy density in batteries, capable of maximizing the benefit by changing the paradigm from nano‐ to micron‐sized Si particles. Nevertheless, intrinsic structural instability remains a significant barrier to its practical application, especially for larger Si particles. Here, a covalently interconnected system is reported employing Si microparticles (5 µm) and a highly elastic gel polymer electrolyte (GPE) through electron beam irradiation. The integrated system mitigates the substantial volumetric expansion of pure Si, enhancing overall stability, while accelerating charge carrier kinetics due to the high ionic conductivity. Through the cost‐effective but practical approach of electron beam technology, the resulting 500 mAh‐pouch cell showed exceptional stability and high gravimetric/volumetric energy densities of 413 Wh kg−1, 1022 Wh L−1, highlighting the feasibility even in current battery production lines.

The gastrointestinal tract is the most common extranodal site for lymphomas, and mucosa-associated lymphoid tissue lymphoma is the second most common histological lymphoma subtype. However, primary esophageal mucosa-associated lymphoid tissue lymphomas are extremely rare. Few such cases are documented, and the reports demonstrate inconsistent diagnostic and therapeutic strategies. Herein, a 54-year-old man was referred to our hospital for treatment of dysphagia. Esophagogastroduodenoscopy revealed a large, horseshoe-shaped subepithelial mass in the upper esophagus. Endoscopic ultrasonography and computed tomography revealed that the mass was well-demarcated and confined to the muscularis mucosa, with no abnormalities in other organs or lymph nodes. The mass was presumptively diagnosed as benign, and the patient underwent endoscopic mucosal dissection for pathological confirmation and symptom relief. Pathological examination of the dissection specimen revealed that it was a primary esophageal mucosa-associated lymphoid tissue lymphoma. As the patient had an elevated immunoglobulin G level and Helicobacter pylori infection, we administered adjuvant eradication therapy. The patient remains under surveillance and is free of lymphoma recurrence 36 months postoperatively. This case report demonstrates that endoscopic resection and H. pylori eradication are effective treatment strategies for early-stage esophageal mucosa-associated lymphoid tissue lymphoma.

Advancements in remote medical technologies and smart devices have led to expectations of contactless rehabilitation. Conventionally, rehabilitation requires clinicians to perform routine muscle function assessments with patients. However, assessment results are difficult to cross-reference owing to the lack of a gold standard. Thus, the application of remote smart rehabilitation systems is significantly hindered. This study analyzes the factors affecting the real-time evaluation of muscle function based on biometric sensor data so that we can provide a basis for a remote system. We acquired real clinical stroke patient data to identify the meaningful features associated with normal and abnormal musculature. We provide a system based on these emerging features that assesses muscle functionality in real time via streamed biometric signal data. A system view based on the amount of data, data processing speed, and feature proportions is provided to support the production of a rudimentary remote smart rehabilitation system.

Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors that are effective against ovarian and breast cancers with breast cancer susceptibility gene (BRCA) mutations have undesirable side effects, such as hematological toxicity. AZD5305, a selective PARP1 inhibitor currently in Phase 1/2 clinical trials, may avoid the side effects caused by PARP2. However, the in vivo pharmacokinetic characteristics of AZD5305 and its bioanalytical methods are unknown. Therefore, a method based on liquid chromatography with tandem mass spectroscopy (LC–MS/MS) was developed and validated to quantify AZD5305 in plasma of mice. Optimal chromatographic separation in terms of peak intensity and symmetry was acquired using a 4-µm Polar-RP 80 Å (2.0 × 150 mm) column with ammonium acetate (5 mM) in distilled water–acetonitrile (50:50, v/v). The retention times of AZD5305 and internal standard (IS; olaparib) were 1.82 min and 1.99 min, respectively. Detection was carried out via triple quadrupole mass spectrometry in positive ion mode employing multiple reaction monitoring transitions at m/z 407.0 → 376.0 for AZD5305 and m/z 435.0 → 281.2 for the IS. The LC–MS/MS method was linear in the range 1–1000 ng/mL with a correlation coefficient ≥ 0.990 and showed acceptable values of major parameters including accuracy, precision, and recovery. Additionally, AZD5305 showed high stability under various conditions. The in vivo and in vitro pharmacokinetics of AZD5305 were successfully characterized by employing the validated LC–MS/MS method. A high level of drug exposure and linear pharmacokinetics were observed after intravenous (IV) bolus and oral administration (PO) of AZD5305 at 0.1–1 mg/kg and 0.1–3 mg/kg, respectively. The bioavailability was close to 100%, and the metabolic stability of AZD5305 in hepatic microsomes of mice and humans was very high. These results may contribute to the improvement of PARP inhibitors that are used to treat malignancies originating from BRCA mutations.

In this study, we propose a method for predicting welding deformation caused by multi-pass welding using the thermal elastic–plastic finite element method (TEP-FEM) by considering the interpass temperature. This method increases the interpass temperature, which has not been considered in the existing TEP-FEM, from 200 °C to 1000 °C, and simultaneously performs thermal and mechanical analyses. In addition, this method can also evaluate temperature history and the time it takes to weld. By predicting the welding deformation using this method, angular distortion prediction was reduced from 16.75 mm to 10.9 mm compared to the case where the interpass temperature was cooled to room temperature. Additionally, the deformation error was significantly reduced from 6.14% to 2.92% compared to that of the strain as directed boundary method used in a previous study. Additionally, our research demonstrated that interpass temperatures above 800 °C can result in increased deformation errors. In conclusion, it is essential to select an appropriate temperature to minimize deformation error.

Head and neck cancer ranks as the sixth-most common malignancy worldwide, characterized by high mortality and recurrence rates. Research studies indicate that molecular diagnostics play a crucial role in the early detection and prognostic evaluation of these diseases. This study aimed to identify potential biomarkers for head and neck cancer and elucidate their interactions with miRNAs and possible therapeutic drugs. Four drivers, namely, FN1, IL1A, COL1A1, and MMP9, were identified using network biology and machine learning approaches. Gene set variation analysis (GSVA) showed that these genes were significantly involved in different biological processes and pathways, including coagulation, UV-response-down, apoptosis, NOTCH signaling, Wnt-beta catenin, and other signal pathways. The diagnostic value of these hub genes was validated using receiver operating characteristic (ROC) curves. The top interactive miRNAs, including miR-128-3p, miR-218-5p, miR-214-3p, miR-124-3p, miR-129-2-3p, and miR-1-3p, targeted the key genes. Furthermore, the interaction between the key genes and drugs was also identified. In summary, the key genes and miRNAs or drugs reported in this study might provide valuable information for potential biomarkers to increase the prognosis and diagnosis of head and neck cancer.

“Organoids”, three-dimensional self-organized organ-like miniature tissues, are proposed as intermediary models that bridge the gap between animal and human studies in drug development. Despite recent advancements in organoid model development, studies on toxicity using these models are limited. Therefore, in this study, we aimed to analyze the functionality and gene expression of pre- and post-differentiated human hepatic organoids derived from induced pluripotent stem cells and utilize them for toxicity assessment. First, we confirmed the functional similarity of this hepatic organoid model to the human liver through various functional assessments, such as glycogen storage, albumin and bile acid secretion, and cytochrome P450 (CYP) activity. Subsequently, utilizing these functionally validated hepatic organoids, we conducted toxicity evaluations with three hepatotoxic substances (ketoconazole, troglitazone, and tolcapone), which are well known for causing drug-induced liver injury, and three non-hepatotoxic substances (sucrose, ascorbic acid, and biotin). The organoids effectively distinguished between the toxicity levels of substances with and without hepatic toxicity. We demonstrated the potential of hepatic organoids with validated functionalities and genetic characteristics as promising models for toxicity evaluation by analyzing toxicological changes occurring in hepatoxic drug-treated organoids.