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Abstract Background Chest pain as the primary manifestation of epilepsy is extremely rare and has only been reported once to date. Case presentation We herein describe a 47-year-old woman with recurrent chest pain for 3 years. The cause of her chest pain remained elusive despite extensive investigations including comprehensive cardiac work-up. She was referred to the neurology clinic for one episode of confusion. Video-electroencephalographic monitoring detected unequivocal ictal changes during her habitual chest pain events. She has remained chest pain (seizure) free with a single antiseizure drug. Conclusions This case underlines the importance of epilepsy as a rare yet treatable cause of recurrent chest pain. Further studies are required to determine the pathophysiology of ictal chest pain.

Objective: The aim of this study is to investigate changes in metabolic networks based on fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with drug-resistant temporal lobe epilepsy (TLE) (with and without hippocampal sclerosis [HS]) when compared with healthy controls. Methods: We retrospectively enrolled 30 patients with drug-resistant temporal lobe epilepsy (17 patients with HS and 13 patients without HS) and 39 healthy controls. All subjects underwent interictal FDG-PET scans, which were analyzed to obtain metabolic connectivity using graph theoretical analysis. We investigated the differences in metabolic connectivity between patients with drug-resistant TLE (with and without HS) and healthy controls. Results: When compared with healthy controls, TLE patients with HS showed alterations of global and local metabolic connectivity. When considering global connectivity, TLE patients with HS had a decreased average degree with increased modularity. When considering local connectivity, TLE patients with HS displayed alterations of betweeness centrality in widespread regions. However, there were no alterations of global metabolic connectivity in TLE patients without HS when compared with healthy controls. In addition, when compared to TLE patients without HS, TLE patients with HS had increased modularity. Significance: Our study demonstrates more severe alterations in metabolic networks based on FDG-PET in TLE patients with HS than in those without HS and healthy controls. This may represent distinct epileptic networks in TLE patients with HS versus those without HS, although both are drug-resistant focal epilepsy.

Abstract Polygenic risk score (PRS) and rare monogenic variant screening are valuable tools for predicting cancer risk and identifying individuals at high risk. Integrating both common and rare genetic variants is crucial for accurate risk assessment. However, estimating the impacts of rare variants on cancer and combining them with PRS remains challenging. Here, we analyze 454,711 exome sequencing and 487,409 array UK Biobank samples, focusing on breast and prostate cancers. We introduce an expanded PRS (EPRS) approach, yielding a systematic model for more effective risk stratification. By prioritizing and clustering genes with cancer-specific rare variants based on odds ratios and population-attributable fraction, we refine risk stratification by combining both monogenic and polygenic effects. Individuals in high-PRS groups with rare high-impact gene variants show up to 15- and 22-fold higher risk for breast and prostate cancers, respectively, compared to those in the intermediate-PRS groups without rare variants. Combined risk profiles vary across distinct rare variant clusters within the same PRS group for both cancers. Our EPRS approach enhances risk stratification for breast and prostate cancers, offering important insights for future research and potential applications to other cancer types.

Abstract This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C

NORM is used as a raw material in various industries worldwide. According to the IAEA, radiological effects may occur in the environment due to raw materials and by-products generated from NORM industries. The objective of this study was to assess radiological environmental impact of the phosphate processing industry to identify the radiological effects on the general public. The resident farmer scenario was chosen as the exposure scenario due to the living characteristics of the public around the facility and the conservatism of the assessment. The RESRAD-OFFSITE code was used to evaluate the radiation dose to the public. The maximum radiation dose to the public was 6.13 × 10−3 mSv/y. Main exposure pathways were aquatic food ingestion, radon inhalation, and meat ingestion. The uranium series accounted for about 99 % of the total radiation dose, while the thorium series and K-40 nuclides accounted for less than 1 %. These study results can be used for management of radiological impact to the public around domestic NORM industries.

Abstract Background To evaluate the diagnostic characteristics of tryptophanyl tRNA synthetase (WRS) for the diagnosis of septic arthritis of the knee joint and to determine whether it is a reliable and sensitive synovial biomarker for discriminating septic arthritis from other types of arthritis. Methods Patients joint effusions for which septic arthritis was suspected were prospectively recruited between January 2019 and September 2020. A total of 9 patients had septic arthritis, 6 had acute gout attack, 1 had an acute flare of chronic rheumatic arthritis, and 46 had pseudogout or reactive arthropathy. Traditional inflammatory markers were measured, and their diagnostic abilities were compared. Neutrophil count, C-reactive protein (CRP) level, WRS, and human neutrophil α-defensin levels were assessed in the synovial fluids. Demographic parameters and biomarkers with a P

Abstract It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1–4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH quintiles and poor functional outcome was modified by stroke severity (p-for-interaction = 0.008). In mild stroke (n = 4994), WMH quintiles associated with the 3-month outcome in a dose-dependent manner for the 2nd to 5th quintile versus the 1st quintile, with adjusted-odds-ratios (aOR [95% confidence interval]) being 1.29 [0.96–1.73], 1.37 [1.02–1.82], 1.60 [1.19–2.13], and 1.89 [1.41–2.53], respectively. In moderate-to-severe stroke (n = 3924), however, there seemed to be a threshold effect: only the highest versus the lowest WMH quintile was significantly associated with poor functional outcome (aOR 1.69 [1.29–2.21]). WMH burden aggravates 3-month functional outcome after mild stroke, but has a lesser modulatory effect for moderate-to-severe stroke, likely due to saturation effects.

Abstract We report a novel deep learning (DL) method for classifying inorganic compounds using 3D electron density data. We transform Density Functional Theory (DFT)-derived CHGCAR files from the Materials Project (MP) and experimental data from the Inorganic Crystal Structure Database (ICSD) into point clouds and sparse tensors, optimized for use in DL models such as PointNet and Sparse 3D CNN. This approach effectively overcomes the limitations of handling the dense 3D data, a common challenge in DL. Contrasting with traditional 1D or 2D X-ray diffraction (XRD) patterns that necessitate complex reciprocal space analysis, our method utilizes 3D density data for direct interpretation in real lattice space. This shift significantly enhances classification accuracy, outperforming traditional XRD-driven DL methods. We achieve accuracies of 97.28%, 90.77%, and 90.10% for crystal system, extinction group, and space group classifications, respectively. Our 3D electron density-based DL approach not only showcases improved accuracy but also contributes a more intuitive and effective framework for materials discovery.

The effect of music therapy on cognitive function has been widely reported; however, its clinical implications remain controversial. Performing therapeutic musical activities in groups using individualized instruments can help overcome the issues of engagement and compliance. We aimed to evaluate the effect of a cognitive intervention with musical stimuli using digital devices on mild cognitive impairment (MCI). In this prospective study, 24 patients with MCI (intervention group, 12; and control group, 12) were enrolled. We developed an electronic device with musical instruments and the Song-based Cognitive Stimulation Therapy protocol (SongCST). Patients in the intervention group underwent a 10-week cognitive intervention involving musical stimuli generated by our device. Effect of the intervention on cognitive function was evaluated by the Mini-Mental State Examination-Dementia Screening (MMSE-DS), Montreal Cognitive Assessment-Korean (MOCA-K), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB). In the intervention group, MMSE-DS and MOCA-K scores improved significantly after the 10-week intervention. The changes in MOCA-K and CDR-SB scores were significantly different between the intervention and control groups. Our study showed that music therapy with digital devices has a positive effect on the executive function and overall disease severity in patients with MCI. Our study can facilitate individualization of music therapy using digital devices in groups.

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 (

Background Perfusion imaging (PI) serves as a valuable tool for triaging patients with acute ischemic stroke for endovascular treatment (EVT). This study aims to investigate trends in PI use and its impacts on EVT rates and clinical outcomes, particularly focusing on variations across different time windows. Methods Data from a prospective, nationwide, acute stroke registry in South Korea were analyzed retrospectively. PI was regarded as treatment‐decision imaging when conducted either (1) prior to EVT, or (2) within 3 hours from hospital arrival in patients not receiving EVT. The study spanned 3 epochs: 2011–2014, 2015–2017, and 2018–2021. Based on the time from onset to arrival, patients were categorized into 2 time windows: early (0–6 hours) and late (6–24 hours). We evaluated EVT rates and clinical outcomes in patients with anterior large vessel occlusion. Results From 2011 to 2021 among 49 449 patients with acute ischemic stroke presenting within 24 hours of onset, PI use rates declined from 36.9% to 30.1%. In the early window, rates dropped from 48.4% to 32.4%, whereas in the late window, they increased from 23.5% to 27.8%. Factors such as older age, atrial fibrillation, anterior large vessel occlusion, and severe stroke were associated with higher rates in the late window. Conversely, younger age and male sex were associated with higher rates in the early window. For patients with anterior large vessel occlusion, PI use increased the likelihood of receiving EVT in the late window and minimized the risk of symptomatic intracranial hemorrhage in the early window. However, 3‐month functional outcomes and mortality were. unaffected. Conclusion The study revealed distinct trends in PI use across early and late time windows, indicating varying roles of PI in these time frames. However, the definitive value and necessity of PI in guiding EVT decision‐making remain unclear, underscoring the need for further research

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except “cough,” were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

The occurrence of an abdominal wall hematoma caused by abdominal paracentesis in patients with liver cirrhosis is rare. This paper presents a case of an abdominal wall hematoma caused by abdominal paracentesis in a 67-year-old woman with liver cirrhosis with a review of the relevant literature. Two days prior, the patient underwent abdominal paracentesis for symptom relief for refractory ascites at a local clinic. Upon admission, a physical examination revealed purpuric patches with swelling and mild tenderness in the left lower quadrant of the abdominal wall. Abdominal computed tomography revealed advanced liver cirrhosis with splenomegaly, tortuous dilatation of the para-umbilical vein, a large volume of ascites, and a large acute hematoma at the left lower quadrant of the abdominal wall. An external iliac artery angiogram showed the extravasation of contrast media from the left deep circumflex iliac artery. Embolization of the target arterial branches using N-butyl-2-cyanoacrylate was then performed, and the bleeding was stopped. The final diagnosis was an abdominal wall hematoma from the left deep circumflex iliac artery after abdominal paracentesis in a patient with liver cirrhosis.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

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.

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.

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.