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Abstract Minimally invasive plate osteosynthesis is the most commonly used minimally invasive surgery technique for tibial fractures, possibly involving single or dual plate methods. Herein, we performed a finite element analysis to investigate plate strength according to the plate type, length, and presence of a fibula by constructing a three-dimensional tibia model. A thickness of 20 mm was cut 50 mm distal from the lateral plateau, and the ligaments were created. Plates were modeled with lengths of 150, 200, and 250 mm and mounted to the tibia. Screws were arranged to avoid overlapping in the dual plating. The von-Mises stress applied to the plates was measured by applying a load of 1 body weight. Dual plates showed the least stress with low displacement, followed by medial and lateral plates. As the plate length increased, the average stress gradually decreased, increasing plate safety. The difference in the influence of the fibula depending on the presence of proximal fibula osteotomy showed that the average stress increased by 35% following proximal fibula osteotomy in the D1(Plate type: Dual plate, Medial plate length: 150 mm, Lateral plate length: 200 mm, Non Proximal fibula osteotomy) and D1P(Plate type: Dual plate, Medial plate length: 150 mm, Lateral plate length: 200 mm, Proximal fibula osteotomy) models, confirming the necessity of the fibula model. There is no consensus guideline for treatment of this kind of fracture case. A single fracture plate can decrease the risk of skin damage, ligament damage, and wound infection, but because of its design, it cannot provide sufficient stability and satisfactory reduction of the condylar fragment, especially in cases of comminution or coronal fracture. So, these results will help clinicians make an informed choice on which plate to use in patients with tibial fractures.

Abstract More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.

Abstract Background The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation. Results Genetically engineered Tat-A86, featuring 16 copies of the interleukin-4 receptor (IL-4R)-binding peptide (AP1), Tat for tumor penetration, and an elastin-like polypeptide (ELP) for presenting target ligands and ensuring stability, served as the basis for this delivery system. Comparative groups, including Tat-E60 and A86, were employed to discern differences in binding and penetration. The designed ELP-based nanoparticle Tat-A86 effectively condensed miRNA, forming stable nanocomplexes under physiological conditions. The miRNA/Tat-A86 formulation bound specifically to tumor cells and facilitated stable miRNA delivery into them, effectively inhibiting tumor growth. The efficacy of miRNA/Tat-A86 was further evaluated using three-dimensional spheroids of lewis lung carcinoma (LLC) as in vitro model and LLC tumor-bearing mice as an in vivo model. It was found that miRNA/Tat-A86 facilitates effective cell killing by markedly improving miRNA penetration, leading to a substantial reduction in the size of LLC spheroids. Compared to other controls, Tat-A86 demonstrated superior efficacy in suppressing the growth of 3D cellular aggregates. Moreover, at equivalent doses, miRNA-34a delivered by Tat-A86 inhibited the growth of LLC cells in allograft mice. Conclusions Overall, these studies demonstrate that Tat-A86 nanoparticles can deliver miRNA systemically, overcoming the basic hurdles impeding miRNA delivery by facilitating both miRNA uptake and stability, ultimately leading to improved therapeutic effects. Graphical Abstract

Abstract Background Mesenchymal stem cells (MSCs) play important roles in tissue homeostasis by providing a supportive microenvironmental niche for the hematopoietic system. Cigarette smoking induces systemic abnormalities, including an impeded recovery process after hematopoietic stem cell transplantation. However, the role of cigarette smoking-mediated alterations in MSC niche function have not been investigated. Methods In the present study, we investigated whether exposure to cigarette smoking extract (CSE) disrupts the hematopoietic niche function of MSCs, and pathways impacted. To investigate the effects on bone marrow (BM)-derived MSCs and support of hematopoietic stem and progenitor cells (HSPCs), mice were repeatedly infused with the CSE named 3R4F, and hematopoietic stem and progenitor cells (HSPCs) supporting function was determined. The impact of 3R4F on MSCs at cellular level were screened by bulk-RNA sequencing and subsequently validated through qRT-PCR. Specific inhibitors were treated to verify the ROS or NLRP3-specific effects, and the cells were then transplanted into the animal model or subjected to coculture with HSPCs. Results Both direct ex vivo and systemic in vivo MSC exposure to 3R4F resulted in impaired engraftment in a humanized mouse model. Furthermore, transcriptomic profile analysis showed significantly upregulated signaling pathways related to reactive oxygen species (ROS), inflammation, and aging in 3R4F-treated MSCs. Notably, ingenuity pathway analysis revealed the activation of NLRP3 inflammasome signaling pathway in 3R4F-treated MSCs, and pretreatment with the NLRP3 inhibitor MCC950 rescued the HSPC-supporting ability of 3R4F-treated MSCs. Conclusion In conclusion, these findings indicate that exposure to CSE reduces HSPCs supportive function of MSCs by inducing robust ROS production and subsequent NLRP3 activation.

Abstract In recent years, the utility of polygenic risk scores (PRS) in forecasting disease susceptibility from genome-wide association studies (GWAS) results has been widely recognised. Yet, these models face limitations due to overfitting and the potential overestimation of effect sizes in correlated variants. To surmount these obstacles, we devised the Stacked Neural Network Polygenic Risk Score (SNPRS). This novel approach synthesises outputs from multiple neural network models, each calibrated using genetic variants chosen based on diverse p-value thresholds. By doing so, SNPRS captures a broader array of genetic variants, enabling a more nuanced interpretation of the combined effects of these variants. We assessed the efficacy of SNPRS using the UK Biobank data, focusing on the genetic risks associated with breast and prostate cancers, as well as quantitative traits like height and BMI. We also extended our analysis to the Korea Genome and Epidemiology Study (KoGES) dataset. Impressively, our results indicate that SNPRS surpasses traditional PRS models and an isolated deep neural network in terms of accuracy, highlighting its promise in refining the efficacy and relevance of PRS in genetic studies.

Background To investigate the real-world safety and effectiveness of dulaglutide in Korean adults with type 2 diabetes mellitus (T2DM). Methods This was a real-world, prospective, non-interventional post-marketing safety study conducted from May 26, 2015 to May 25, 2021 at 85 Korean healthcare centers using electronic case data. Data on patients using dulaglutide 0.75 mg/0.5 mL or the dulaglutide 1.5 mg/0.5 mL single-use pens were collected and pooled. The primary objective was to report the frequency and proportion of adverse and serious adverse events that occurred. The secondary objective was to monitor the effectiveness of dulaglutide at 12 and 24 weeks by evaluating changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose, and body weight. Results Data were collected from 3,067 subjects, and 3,022 subjects who received ≥1 dose (of any strength) of dulaglutide were included in the safety analysis set (53% female, mean age 56 years; diabetes duration 11.2 years, mean HbA1c 8.8%). The number of adverse events reported was 819; of these, 68 (8.3%) were serious adverse events. One death was reported. Adverse events were mostly mild in severity; 60.81% of adverse events were considered related to dulaglutide. This study was completed by 72.73% (2,198/3,022) of subjects. At 12/24 weeks there were significant (P

Background/Aims: Reports on the association between sarcopenic visceral obesity and non-alcoholic fatty liver disease (NAFLD)-associated morbidities remain scarce. We investigated the association between sarcopenia and visceral obesity, and the influence of this association on hepatic and coronary comorbidities. Methods: The appendicular skeletal muscle mass to visceral fat area ratio (SV ratio) was evaluated using bioelectric impedance analysis. NAFLD and significant liver fibrosis were assessed using transient elastography, and high atherosclerotic cardiovascular disease (ASCVD) risk was defined as a 10-year ASCVD risk score >10%. Sarcopenia was defined as appendicular skeletal muscle mass adjusted by body mass index (

Dual left anterior descending artery (LAD) is a rare congenital coronary artery anomaly with a prevalence of approximately 1% in the general population. To date, 10 types of dual LAD artery anomalies have been reported. Among these, type 4 is one of the rarest. Knowledge and recognition of the dual LAD artery are important for correct diagnosis and planning of coronary bypass surgery and percutaneous coronary intervention. We report a case of a 59-year-old male with type 4 dual LAD artery who presented with dyspepsia and sweating for several months and had approximately 50%–70% stenosis in a major diagonal branch off the short LAD artery.

Objective This study aimed to compare the accuracy of robotic spine surgery and conventional pedicle screw fixation in lumbar degenerative disease. We evaluated clinical and radiological outcomes to demonstrate the noninferiority of robotic surgery. Methods This study employed propensity score matching and included 3 groups: robot-assisted mini-open posterior lumbar interbody fusion (PLIF) (robotic surgery, RS), c-arm guided minimally invasive surgery transforaminal lumbar interbody fusion (C-arm guidance, CG), and freehand open PLIF (free of guidance, FG) (54 patients each). The mean follow-up period was 2.2 years. The preoperative spine condition was considered. Accuracy was evaluated using the Gertzbein-Robbins scale (GRS score) and Babu classification (Babu score). Radiological outcomes included adjacent segmental disease (ASD) and mechanical failure. Clinical outcomes were assessed based on the visual analogue scale, Oswestry Disability Index, 36-item Short Form health survey, and clinical ASD rate. Results Accuracy was higher in the RS group (p < 0.01) than in other groups. The GRS score was lower in the CG group, whereas the Babu score was lower in the FG group compared with the RS group. No significant differences were observed in radiological and clinical outcomes among the 3 groups. Regression analysis identified preoperative facet degeneration, GRS and Babu scores as significant variables for radiological and clinical ASD. Mechanical failure was influenced by the GRS score and patients’ age. Conclusion This study showed the superior accuracy of robotic spine surgery compared with conventional techniques. When combined with minimally invasive surgery, robotic surgery is advantageous with reduced ligament and muscle damage associated with traditional open procedures.

Background Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable remission in patients with B-cell malignancies. However, its efficacy in treating solid tumors remains limited. Here, we investigated a combination therapy approach using an engineered long-acting interleukin (IL)-7 (rhIL-7-hyFc or NT-I7) and CAR-T cells targeting three antigens, glypican-2 (GPC2), glypican-3 (GPC3), and mesothelin (MSLN), against multiple solid tumor types including liver cancer, neuroblastoma, ovarian cancer, and pancreatic cancer in mice.Methods CAR-T cells targeting GPC2, GPC3, and MSLN were used in combination with NT-I7 to assess the anticancer activity. Xenograft tumor models, including the liver cancer orthotopic model, were established using NOD scid gamma mice engrafted with cell lines derived from hepatocellular carcinoma, neuroblastoma, ovarian cancer, and pancreatic cancer. The mice were monitored by bioluminescence in vivo tumor imaging and tumor volume measurement using a caliper. Immunophenotyping of CAR-T cells on NT-I7 stimulation was evaluated for memory markers, exhaust markers, and T-cell signaling molecules by flow cytometry and western blotting.Results Compared with the IL-2 combination, preclinical evaluation of NT-I7 exhibited regression of solid tumors via enhanced occupancy of CD4+ CAR-T, improved T-cell expansion, reduced exhaustion markers (programmed cell death protein 1 or PD-1 and lymphocyte-activation gene 3 or LAG-3) expression, and increased generation of stem cell-like memory CAR-T cells. The STAT5 pathway was demonstrated to be downstream of NT-I7 signaling, mediated by increased expression of the IL-7 receptor expression in CAR-T cells. Furthermore, CAR-T cells improved efficacy against tumors with low antigen density when combined with NT-I7 in mice, presenting an avenue for patients with heterogeneous antigenic profiles.Conclusion This study provides a rationale for NT-I7 plus CAR-T cell combination therapy for solid tumors in humans.

BackgroundsFreezing of gait (FoG) is a common and debilitating symptom of Parkinson's disease (PD) that can lead to falls and reduced quality of life. Wearable sensors have been used to detect FoG, but current methods have limitations in accuracy and practicality. In this paper, we aimed to develop a deep learning model using pressure sensor data from wearable insoles to accurately detect FoG in PD patients.MethodsWe recruited 14 PD patients and collected data from multiple trials of a standardized walking test using the Pedar insole system. We proposed temporal convolutional neural network (TCNN) and applied rigorous data filtering and selective participant inclusion criteria to ensure the integrity of the dataset. We mapped the sensor data to a structured matrix and normalized it for input into our TCNN. We used a train-test split to evaluate the performance of the model.ResultsWe found that TCNN model achieved the highest accuracy, precision, sensitivity, specificity, and F1 score for FoG detection compared to other models. The TCNN model also showed good performance in detecting FoG episodes, even in various types of sensor noise situations.ConclusionsWe demonstrated the potential of using wearable pressure sensors and machine learning models for FoG detection in PD patients. The TCNN model showed promising results and could be used in future studies to develop a real-time FoG detection system to improve PD patients' safety and quality of life. Additionally, our noise impact analysis identifies critical sensor locations, suggesting potential for reducing sensor numbers.

Aim: We validated the prognostic performance of neuron-specific enolase (NSE) according to the recommended values in cardiac arrest (CA) survivors. Methods: We analyzed the data of adult CA survivors who underwent targeted temperature management between January 2014 and December 2020. We measured the NSE level 48 h and 72 h after CA. We performed receiver operating characteristics (ROC) and used the reference value (17 μg/L) and the guidelines-suggested value (60 μg/L) as thresholds. The primary outcome was 6-month neurological outcomes with Cerebral Performance Category (CPC), dichotomized into good (CPC 1 or 2) or poor (CPC 3–5). Results: Of the 513 included patients, 346 (67.4 %) patients had poor neurological outcomes. The area under ROC (AUC) of NSE at 48 h was 0.887 (95 % confidence intervals [CIs], 0.851–0.909) with the Youden index of 35.6 μg/L. A false positive rate (FPR) of

Aims In South Korea, to care for patients with dementia, a new dementia-specific nursing institution has been established that, unlike general nursing institutions, uses shared living rooms and provides customized programs for dementia. This study aims to investigate the effectiveness of dementia-specific nursing institutions. For this purpose, whether psychotropic drugs (antipsychotics, antidepressants, sedatives, mood stabilizers) used to treat behavioral and psychological symptoms of dementia (BPSD) are prescribed, and the mortality and morbidity rates mentioned as side effects of psychotropic drugs (cerebrovascular disease, fall-related fractures, pneumonia, pressure ulcers) varied depending on the use of a dementia-specific nursing institution. Methods Using the National Health Insurance Service's customized and Long-Term Care Insurance databases for older people, we collected data over the four years since the introduction of dementia-specific nursing institutions. Among patients with dementia aged 65 years or older, those who used dementia-specific nursing institutions and those who used general nursing institutions were matched for gender, age, history of cerebrovascular disease, disability, comorbidities, and history of taking psychotropic drugs. Thus, 835 users of dementia-specific nursing institutions and 2,505 users of general nursing institutions were analyzed. During the study period, the subjects' use of psychotropic drugs, mortality, and morbidity (cerebrovascular disease, fall-related fractures, pneumonia, and pressure ulcers) were determined. After controlling for variables such as Activities of Daily Living (ADL) scores, the effect of using a dementia-specific nursing institution on mortality and morbidity was analyzed using a logistic regression model. Results Users of dementia-specific nursing institutions were more likely to be prescribed antipsychotics, antidepressants, and sedatives during the study period compared with users of general nursing institutions. Also, users of dementia-specific nursing institutions had a lower mortality rate and lower morbidity rates of pneumonia and pressure ulcers than users of general nursing institutions. Conclusion Users of dementia-specific nursing institutions had significantly lower mortality rates and morbidity rates of pneumonia and pressure ulcers. This is attributed to dementia-specific nursing institutions encouraging social interaction and physical activity by providing shared living rooms and specialized programs catered towards patients with dementia. However, since the influence of other confounding variables cannot be ruled out, more precisely designed research is needed in the future.

Background:. Falls after orthopaedic surgery can cause serious injuries, which lengthen hospital stays and increase medical expenses. This has prompted hospitals to implement various fall-prevention protocols. The aims of this study were to determine the incidence of in-hospital falls after spine surgery, to analyze the overall risk factors, to discern factors that have a major influence on falls, and to evaluate the effectiveness of the fall-prevention protocol that we implemented. Methods:. This was a retrospective, single-center study including patients who underwent spine surgery from January 2011 to November 2021 at the National Health Insurance Service Ilsan Hospital (NHISIH) in Goyang, Republic of Korea. Reported falls among these patients were examined. Patient demographics; surgery type, date, and diagnosis; and fall date and time were evaluated. Results:. Overall, 5,317 spine surgeries were performed, and 128 in-hospital falls were reported (overall incidence: 2.31%). From the multivariable analyses, older age and American Society of Anesthesiologists (ASA) score were identified as independent risk factors for in-hospital patient falls (multivariable adjusted hazard ratio [aHR] for age 70 to 79 years, 1.021 [95% confidence interval (CI), 1.01 to 1.031]; for age ≥80 years, 1.035 [1.01 to 1.06]; and for ASA score of 3, 1.02 [1.01 to 1.031]). Similar results were seen in the subgroup who underwent primary surgery. Within 2 weeks following surgery, the highest frequency of falls occurred at 3 to 7 days postoperatively. The lowest fall rate was observed in the evening (6 to 10 p.m.). Morbidities, including rib, spine, and extremity fractures, were recorded for 14 patients, but none of these patients underwent operative treatment related to the fall. The NHISIH implemented a comprehensive nursing care service in May 2015 and a fall protocol in May 2017, but the annual incidence rate did not improve. The fall rate was higher after thoracolumbar surgeries (2.47%) than after cervical surgeries (1.20%). Moreover, a higher fall rate was observed in thoracolumbar cases with a greater number of fusion levels and revision spine surgeries. Conclusions:. Patients with advanced age, more comorbidities, a greater number of fusion levels, and revision surgeries and who are female are more vulnerable to in-hospital falls after spine surgery. Novel strategies that target these risk factors are warranted. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

This paper presents an automated machine learning framework designed to assist hydrologists in detecting anomalies in time series data generated by sensors in a research watershed in the northeastern United States critical zone. The framework specifically focuses on identifying peak-pattern anomalies, which may arise from sensor malfunctions or natural phenomena. However, the use of classification methods for anomaly detection poses challenges, such as the requirement for labeled data as ground truth and the selection of the most suitable deep learning model for the given task and dataset. To address these challenges, our framework generates labeled datasets by injecting synthetic peak patterns into synthetically generated time series data and incorporates an automated hyperparameter optimization mechanism. This mechanism generates an optimized model instance with the best architectural and training parameters from a pool of five selected models, namely Temporal Convolutional Network (TCN), InceptionTime, MiniRocket, Residual Networks (ResNet), and Long Short-Term Memory (LSTM). The selection is based on the user’s preferences regarding anomaly detection accuracy and computational cost. The framework employs Time-series Generative Adversarial Networks (TimeGAN) as the synthetic dataset generator. The generated model instances are evaluated using a combination of accuracy and computational cost metrics, including training time and memory, during the anomaly detection process. Performance evaluation of the framework was conducted using a dataset from a watershed, demonstrating consistent selection of the most fitting model instance that satisfies the user’s preferences.

Abstract Bioactive glass–ceramic (BGC) cage is a substitute for polyether ether ketone (PEEK) cages in anterior cervical discectomy and fusion (ACDF). Only a few comparative studies exist using PEEK and non-window-type BGC cages (CaO–SiO2–P2O5–B2O3) in single-level ACDF. This study compared PEEK cages filled with autologous iliac bone grafts and BGC cages regarding clinical safety and effectiveness. A retrospective case series was performed on 40 patients who underwent single-level ACDF between October 2020 and July 2021 by a single orthopedic spine surgeon. The spacers used in each ACDF were a PEEK cage with a void filled with an autologous iliac bone graft and a non-window-type BGC cage in 20 cases. The grafts were compared pre-operatively and post-operatively at 6 weeks and 3, 6, and 12 months. Post-operative complications were investigated in each group. Clinical outcome was measured, including Visual Analog Scale (VAS) scores of neck and arm pains, Japanese Orthopedic Association score (JOA), and Neck Disability Index (NDI). Dynamic lateral radiographs were used to assess the inter-spinous motion (ISM) between the fusion segment and subsidence. The fusion status was evaluated using a computed tomography (CT) scan. Overall, 39 patients (19 and 20 patients in the PEEK and BGC groups, respectively) were recruited. Eighteen (94.7%) and 19 (95.0%) patients in the PEEK and BGC groups, respectively, were fused 12 months post-operatively, as assessed by ISM in dynamic lateral radiograph and bone bridging formation proven in CT scan. The PEEK and BGC groups showed substantial improvement in neck and arm VAS, JOA, and NDI scores. No substantial difference was found in clinical and radiological outcomes between the PEEK and BGC groups. However, the operation time was considerably shorter in the BGC group than in the PEEK group. In conclusion, a non-window-type BCG cage is a feasible substitute for a PEEK cage with an autologous iliac bone graft in single-level ACDF.

Screen summarization aims to generate concise textual descriptions that communicate the crucial contents and functionalities of a mobile user interface (UI) screen. A UI screen consists of objects with a hierarchical structure that are tightly interconnected, and each object contains multimodal data such as images, texts, and bounding boxes. Considering these characteristics, previous works encoded the absolute position of objects at the view hierarchy to extract the semantic representation of the UI screen. However, the importance of the hierarchical dependency between objects in the UI structure was overlooked. In this study, we propose an object-wise hierarchical dependency-based Transformer named OHiFormer. OHiFormer considers the objects on the UI screen as tokens in natural language processing and leverages the Transformer to capture the mutual relationships between objects. Moreover, OHiFormer includes a modified self-attention mechanism using structural relative position encoding to represent the hierarchically connected UI. Experimental results demonstrate that OHiFormer outperforms benchmark models in the BLEU 1, BLEU 2, BLEU 3, BLEU 4, ROUGE-L, and CIDEr metrics by 3.63%, 2.1%, 0.12%, 1.8%, 2.38%, and 17.58%, respectively, on the Screen Summarization dataset. Furthermore, our proposed UI structural representation method achieves remarkable performance on complex UIs with numerous objects compared to other structural position encoding methods. Finally, a visualization of the self-attention heatmaps demonstrates how OHiFormer reflects the hierarchical dependencies between objects. By reflecting hierarchical dependencies hidden in the visual layout of the UI, OHiFormer not only improves the quality of summaries but also offers the potential for applications in mobile apps and systems containing numerous interactive objects.

Abstract Background Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support—including protein, calcium, and vitamin D—are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia. Methods This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points. Discussion This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women. Trial registration Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262 .

Abstract Although KRASG12C inhibitors have shown promising activity in lung adenocarcinomas harbouring KRASG12C, acquired resistance to these therapies eventually occurs in most patients. Re-expression of KRAS is thought to be one of the main causes of acquired resistance. However, the mechanism through which cancer cells re-express KRAS is not fully understood. Here, we report that the Hedgehog signal is induced by KRASG12C inhibitors and mediates KRAS re-expression in cancer cells treated with a KRASG12C inhibitor. Further, KRASG12C inhibitors induced the formation of primary cilia and activated the Hedgehog-GLI-1 pathway. GLI-1 binds to the KRAS promoter region, enhancing KRAS promoter activity and KRAS expression. Inhibition of GLI using siRNA or the smoothened (Smo) inhibitor suppressed re-expression of KRAS in cells treated with a KRASG12C inhibitor. In addition, we demonstrate that KRASG12C inhibitors decreased Aurora kinase A (AURKA) levels in cancer cells, and inhibition of AURKA using siRNA or inhibitors led to increased expression levels of GLI-1 and KRAS even in the absence of KRAS inhibitor. Ectopic expression of AURKA attenuated the effect of KRASG12C inhibitors on the expression of GLI-1 and re-expression of KRAS. Together, these findings demonstrate the important role of AURKA, primary cilia, and Hedgehog signals in the re-expression of KRAS and therefore the induction of acquired resistance to KRASG12C inhibitors, and provide a rationale for targeting Hedgehog signalling to overcome acquired resistance to KRASG12C inhibitors.

Introduction: The platelet-to-lymphocyte ratio (PLR) is associated with the inflammatory response in various diseases. However, studies on the use of the PLR for the prognosis of elderly patients with severe trauma are lacking. In this study, we examined the relationship between the PLR and in-hospital mortality in elderly patients with severe trauma. Methods: This retrospective observational study included elderly (≥65 years) patients who were admitted for severe trauma (as defined by an Injury Severity Score [ISS] ≥ 16) between January–December 2022. We conducted multivariate analysis to assess the association between the PLR and in-hospital mortality using logistic regression of relevant covariates. We also performed receiver operating characteristic curve analysis to examine the prognostic performance of the PLR for in-hospital mortality. Results: Among the 222 patients included in the study, the in-hospital mortality rate was 19.4% (43). The PLR of non-survivors was lower than that of survivors (62.1 vs 124.5). The areas under the curve (AUC) of the Glasgow Coma Scale (GCS) score ≤12, ISS, hemoglobin level, and PLR for predicting in-hospital mortality were 0.730 (95% confidence interval [CI] 0.667–0.787), 0.771 (95% CI 0.710–0.824), 0.657 (95% CI 0.591–0.719), and 0.730 (95% CI 0.667–0.788), respectively. The AUC of the PLR was not significantly different from that of GCS score ≤12 and ISS for predicting in-hospital mortality. Multivariate analysis showed that the PLR was independently associated with in-hospital mortality (odds ratio: 0.993; 95% CI 0.987–0.999). Conclusion: Low platelet-to-lymphocyte ratio is independently associated with in-hospital mortality in elderly patients with severe trauma.

Abstract We investigated the difference in optical coherence tomography angiography characteristics between the patients with compressive optic neuropathy (CON, n = 26) and glaucomatous optic neuropathy (GON, n = 26), who were matched for the severity of visual field defect. The peripapillary retinal nerve fiber layer (pRNFL) thickness in the nasal and temporal sectors was thinner in the CON group, whereas the inferior pRNFL thickness was thinner in the GON group. Accordingly, the CON group had lower peripapillary vessel density (pVD) in the nasal and temporal sectors, and the GON group in the inferior sector. In the macular area, the CON group had a thinner macular ganglion cell-inner plexiform layer in the superior and nasal sectors, whereas the GON group in the inferior sector. However, the CON group did not have a lower macular VD than the GON group in any sector, whereas the GON group exhibited lower superficial capillary plexus VD in the superior, inferior, and temporal sectors. Comparison of the structure–vasculature correlation revealed a significant difference in the nasal and temporal peripapillary areas and superior and nasal macular sectors; a decrease in VD was greater in the GON group than in the CON group when the comparable structural change occurred.

Objective Myocardial rupture is a fatal complication of acute myocardial infarction (AMI). Early diagnosis of myocardial rupture is feasible when emergency physicians (EPs) perform emergency transthoracic echocardiography (TTE). The purpose of this study was to report the echocardiographic features of myocardial rupture on emergency TTE performed by EPs in the emergency department (ED). Methods This was a retrospective and observational study involving consecutive adult patients presenting with AMI who underwent TTE performed by EPs in the ED of a single academic medical center from March 2008 to December 2019. Results Fifteen patients with myocardial rupture, including eight (53.3%) with free wall rupture (FWR), five (33.3%) with ventricular septal rupture (VSR), and two (13.3%) with FWR and VSR, were identified. Fourteen of the 15 patients (93.3%) were diagnosed on TTE performed by EPs. Diagnostic echocardiographic features were found in 100% of the patients with myocardial rupture, including pericardial effusion for FWR and a visible shunt on the interventricular septum for VSR. Additional echocardiographic features indicating myocardial rupture were thinning or aneurysmal dilatation in 10 patients (66.7%), undermined myocardium in six patients (40.0%), abnormal regional motions in six patients (40.0%), and pericardial hematoma in six patients (40.0%). Conclusion Early diagnosis of myocardial rupture after AMI is possible using echocardiographic features on emergency TTE performed by EPs.

Considerable evidence has been published since the 2020 Korean Cardiopulmonary Resuscitation Guidelines were reported. The International Liaison Committee on Resuscitation (ILCOR) also publishes the Consensus on CPR and Emergency Cardiovascular Care Science with Treatment Recommendations (CoSTR) summary annually. This review provides expert opinions by reviewing the recent evidence on CPR and ILCOR treatment recommendations. The authors reviewed the CoSTR summary published by ILCOR in 2021 and 2022. PICO (patient, intervention, comparison, outcome) questions for each topic were reviewed using a systemic or scoping review methodology. Two experts were appointed for each question and reviewed the topic independently. Topics suggested by the reviewers for revision or additional description of the guidelines were discussed at a consensus conference. Forty-three questions were reviewed, including 15 on basic life support, seven on advanced life support, two on pediatric life support, 11 on neonatal life support, six on education and teams, one on first aid, and one related to COVID-19. Finally, the current Korean CPR Guideline was maintained for 28 questions, and expert opinions were suggested for 15 questions.

Abstract Integrating different modification strategies into a single step to achieve the desired properties of metal–organic frameworks (MOFs) has been very synthetically challenging, especially in developing advanced MOF/polymer mixed matrix membranes (MMMs). Herein, we report a polymer–MOF (polyMOF) system constructed from a carboxylated polymer with intrinsic microporosity (cPIM-1) ligand. This intrinsically microporous ligand could coordinate with metals, leading to ~100 nm-sized polyMOF nanoparticles. Compared to control MOFs, these polyMOFs exhibit enhanced ultramicroporosity for efficient molecular sieving, and they have better dispersion properties in casting solutions to prepare MMMs. Ultimately, integrating coordination chemistries through the cPIM-1 and polymer-based functionality into porous materials results in polyMOF/PIM-1 MMMs that display excellent CO2 separation performance (surpassing the CO2/N2 and CO2/CH4 upper bounds). In addition to exploring the physicochemical and transport properties of this polyMOF system, scalability has been demonstrated by converting the developed MMM material into large-area (400 cm2) thin-film nanocomposite (TFN) membranes.

Abstract This study suggests a hybrid method based on ResNet50 and vision transformer (ViT) in an age estimation model. To this end, panoramic radiographs are used for learning by considering both local features and global information, which is important in estimating age. Transverse and longitudinal panoramic images of 9663 patients were selected (4774 males and 4889 females with a mean age of 39 years and 3 months). To compare ResNet50, ViT, and the hybrid model, the mean absolute error, mean square error, root mean square error, and coefficient of determination (R2) were used as metrics. The results confirmed that the age estimation model designed using the hybrid method performed better than those using only ResNet50 or ViT. The estimation is highly accurate for young people at an age with distinct growth characteristics. When examining the basis for age estimation in the hybrid model through attention rollout, the proposed model used logical and important factors rather than relying on unclear elements as the basis for age estimation.

The Middle Paleozoic tectonic evolution of the central Korean Peninsula (Gyeonggi Massif, Hongseong-Imjingang, and Okcheon zone of Okcheon Belts) remains controversial. Particularly, the occurrence of high-grade metamorphism and sedimentation need further examination. In this study, we conducted zircon U-Pb-rare earth element analyses from in the ultramafic-mafic complex in the central Korean Peninsula (Cheonan and Gapyeong areas) and the Paleozoic metasedimentary rocks in the Okcheon Zone of the Okcheon Belt to constrain the timing of maximum depositional and metamorphic ages. We also examined the metamorphic P-T-t path from garnet-bearing amphibolite in the central Korean Peninsula by pseudosection modeling and geothermobarometer. The results show that (i) some of the ultramafic-mafic complex and metasedimentary rocks in the central Korean Peninsula formed during the Middle Paleozoic (ca. 450–374 Ma); (ii) garnet-bearing amphibolite underwent successive metamorphism from amphibolite facies condition (7.5–8.0 kbar and 540–630 °C) at pre-peak stage to granulite facies condition (10.9–11.8 kbar and 740–820 °C) at peak stage, and then retrograded into amphibolite facies condition (5.7–7.7 kbar and 530–670 °C) along the clockwise P–T path during ca. 403–362 Ma. This and previous studies suggest that the central Korean Peninsula underwent subduction-related orogenic events during the Middle Paleozoic era, and it is well correlated to those of the orogenic events in the North Qinling belt.

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P

Background: Sex-related disparities in the prevalence of chronic cough have been consistently reported globally, with varying male-to-female ratios. Objectives: This study aimed to evaluate sex-related differences by comparing correlations between cough-related symptoms in males and females of different age groups. Design: Adult patients with chronic cough who completed the Leicester Cough Questionnaire (LCQ) were recruited from 16 respiratory centers. Methods: Correlation networks were constructed based on Spearman’s correlation coefficients in males and females of various age groups. The distinct relationships of cough-related symptoms between subgroups were validated by an independent cohort. Results: A total of 255 patients were enrolled in this study (male-to-female ratio, 1:1.71). The following LCQ items were highly correlated: embarrassment and interference with daily work, anxiety, and interference with overall life enjoyment/feeling of being fed up, interference with daily work and overall life enjoyment, interference with overall life enjoyment and feeling of being fed up, and feeling of being fed up and annoyance to partner/family/friends. The patterns of these correlations between LCQ items varied in males and females of different ages. The strongest interrelationship was observed in male patients aged >50 years old, which was similar to those in the validation cohort. Conclusion: The correlation patterns between cough-related symptoms vary significantly according to age and sex. Understanding the mechanisms underlying the development of cough-related symptoms may facilitate sex- and age-specific strategies for chronic cough.

Background Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT‐AC) in early‐presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT‐AC among the patients with nonminor or late‐presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. Methods and Results In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT‐AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High‐Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet‐Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1–7) were analyzed. In 2008, DAPT‐AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT‐AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10−8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51–14.09], P

Abstract Soft robots require soft actuators for mobility and functionality. To integrate multiple functions in a limited space, researchers are developing multifunctional soft actuators with several functions integrated in one device. This study successfully demonstrates an electroluminescent (EL) soft actuator, a single device with both light‐emitting and actuating capabilities, using liquid dielectric and uniformly dispersed EL phosphor particles. EL phosphor particles are copper‐doped zinc sulfide (ZnS) particles doped with copper. The work is able to disperse the ZnS particles uniformly in the oil by coating the ZnS particles with silica, ensuring consistent luminescence across the device's active area. The performance of the soft actuator is notable, with a strain of 25% and a maximum EL intensity of 23 cd m−2 for a single actuator. When stacking multiple actuators, the intensity exceeds 29 cd m−2. The findings suggest that EL actuator devices will be valuable smart components for soft robots and interactive sensors. They can effectively represent external stimuli through color signals, expanding the capabilities of these systems.