Machine-learning-based models for the optimization of post-cervical spinal laminoplasty outpatient follow-up schedules.

BACKGROUND: Patients undergo regular clinical follow-up after laminoplasty for cervical myelopathy. However, those whose symptoms significantly improve and remain stable do not need to conform to a regular follow-up schedule. Based on the 1-year postoperative outcomes, we aimed to use a machine-learning (ML) algorithm to predict 2-year postoperative outcomes. METHODS: We enrolled 80 patients who underwent cervical laminoplasty for cervical myelopathy. The patients' Japanese Orthopedic Association (JOA) scores (range: 0-17) were analyzed at the 1-, 3-, 6-, and 12-month postoperative timepoints to evaluate their ability to predict the 2-year postoperative outcomes. The patient acceptable symptom state (PASS) was defined as a JOA score ≥ 14.25 at 24 months postoperatively and, based on clinical outcomes recorded up to the 1-year postoperative timepoint, eight ML algorithms were developed to predict PASS status at the 24-month postoperative timepoint. The performance of each of these algorithms was evaluated, and its generalizability was assessed using a prospective internal test set. RESULTS: The long short-term memory (LSTM)-based algorithm demonstrated the best performance (area under the receiver operating characteristic curve, 0.90 ± 0.13). CONCLUSIONS: The LSTM-based algorithm accurately predicted which group was likely to achieve PASS at the 24-month postoperative timepoint. Although this study included a small number of patients with limited available clinical data, the concept of using past outcomes to predict further outcomes presented herein may provide insights for optimizing clinical schedules and efficient medical resource utilization. TRIAL REGISTRATION: This study was registered as a clinical trial (Clinical Trial No. NCT02487901), and the study protocol was approved by the Seoul National University Hospital Institutional Review Board (IRB No. 1505-037-670).

Distinct Cognitive Trajectories According to Amyloid Positivity in Non-Alzheimer Disease Dementias.

BACKGROUND: The clinical effects of ß-amyloid positivity (Aß+) on copathologies in various dementias remain relatively underexamined. Thus, the present study was conducted to investigate the prevalence and clinical effects of Aß+ in subcortical vascular cognitive impairment (SVCI) and frontotemporal dementia (FTD). PATIENTS AND METHODS: We enrolled SVCI (n = 583), FTD (n = 152), and cognitively unimpaired (CU) participants (n = 1,249) who underwent Aß PET scans. The odds of having Aß+ were subsequently compared among the diagnostic groups (CU, SVCI, and FTD) according to age and apolipoprotein E genotype. Additionally, a linear mixed-effects model was used to investigate the effects of Aß+ on cognitive trajectories in SVCI and FTD. RESULTS: Compared with CU, the SVCI group had a higher prevalence of Aß+ in the 75 to 90 years age group (adjusted odds ratio, 1.97; 95% confidence interval, 1.36-2.85; P < 0.001), as well as within the apolipoprotein E ε3/ε3 group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.63; P = 0.001), whereas the FTD group showed no difference in Aß+ prevalence. Aß+ was associated with a worse cognitive trajectory in SVCI (adjusted ß-coefficient = -0.6424; P < 0.001), but not in FTD. CONCLUSIONS: These findings contribute to our understanding of Aß biomarker traits in various dementias in Korea.

Real-Time Imaging Assessment of Stress-Induced Vascular Inflammation Using Heartbeat-Synchronized Motion Compensation.

BACKGROUND: Chronic mental stress accelerates atherosclerosis through complicated neuroimmune pathways, needing for advanced imaging techniques to delineate underlying cellular mechanisms. While histopathology, ex vivo imaging, and snapshots of in vivo images offer promising evidence, they lack the ability to capture real-time visualization of blood cell dynamics within pulsatile arteries in longitudinal studies. METHODS: An electrically tunable lens was implemented in intravital optical microscopy, synchronizing the focal plane with heartbeats to follow artery movements. ApoE-/- mice underwent 2 weeks of restraint stress before baseline imaging followed by 2 weeks of stress exposure in the longitudinal imaging, while nonstressed mice remained undisturbed. The progression of vascular inflammation was assessed in the carotid arteries through intravital imaging and histological analyses. RESULTS: A 4-fold reduction of motion artifact, assessed by interframe SD, and an effective temporal resolution of 25.2 Hz were achieved in beating murine carotid arteries. Longitudinal intravital imaging showed chronic stress led to a 6.09-fold (P=0.017) increase in myeloid cell infiltration compared with nonstressed mice. After 3 weeks, we observed that chronic stress intensified vascular inflammation, increasing adhered myeloid cells by 2.45-fold (P=0.031), while no significant changes were noted in nonstressed mice. Microcirculation imaging revealed increased circulating, rolling, and adhered cells in stressed mice's venules. Histological analysis of the carotid arteries confirmed the in vivo findings that stress augmented plaque area, myeloid cell and macrophage accumulation, and necrotic core volume while reducing fibrous cap thickness indicating accelerated plaque formation. We visualized the 3-dimensional structure of the carotid artery and 4-dimensional dynamics of the venules in the cremaster muscle. CONCLUSIONS: Dynamic focusing motion compensation intravital microscopy enabled subcellular resolution in vivo imaging of blood cell dynamics in beating arteries under chronic restraint stress in real time. This novel technique emphasizes the importance of advanced in vivo imaging for understanding cardiovascular disease.

UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer.

BACKGROUND: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. METHODS: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. RESULTS: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. CONCLUSION: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

Glycerophospholipid remodeling is critical for orthoflavivirus infection.

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.

Spinal Schwannoma Classification Based on the Presumed Origin With Preoperative Magnetic Resonance Images.

OBJECTIVE: Classification guides the surgical approach and predicts prognosis. However, existing classifications of spinal schwannomas often result in a high 'unclassified' rate. Here, we aim to develop a new comprehensive classification for spinal schwannomas based on their presumed origin. We compared the new classification with the existing classifications regarding the rate of 'unclassified'. Finally, we assessed the surgical strategies, outcomes, and complications according to each type of the new classification. METHODS: A new classification with 9 types was created by analyzing the anatomy of spinal nerves and the origin of significant tumor portions and cystic components in preoperative magnetic resonance images. A total of 482 patients with spinal schwannomas were analyzed to compare our new classification with the existing classifications. We defined 'unclassified' as the inability to classify a patient with spinal schwannoma using the classification criteria. Surgical approaches and outcomes were also aligned with our new classification. RESULTS: Our classification uniquely reported no 'unclassified' cases, indicating full applicability. Also, the classification has demonstrated usefulness in predicting the surgical outcome with the approach planned. Gross total removal rates reached 88.0% overall, with type 1 and type 2 tumors at 95.3% and 96.0% respectively. The approach varied with tumor type, with laminectomy predominantly used for types 1, 2, and 9, and facetectomy with posterior fixation used for type 3 tumors. CONCLUSION: The new classification for spinal schwannomas based on presumed origin is applicable to all spinal schwannomas. It could help plan a surgical approach and predict its outcome, compared with existing classifications.

High photocatalytic efficiency of a ZnO nanoplate/Fe2O3 nanospindle hybrid using visible light for methylene blue degradation.

In this work, ZnO nanoplates and Fe2O3 nanospindles were successfully fabricated via a simple hydrothermal method using inorganic salts as precursors. The ZnO/Fe2O3 hybrid was fabricated using a mechanical mixture of two different ZnO : Fe2O3 weight ratios to investigate the effect of weight ratio on catalytic properties. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed that ZnO nanoplates (NPls) are about 20 nm thick with lateral dimensions of 100 × 200 nm, and Fe2O3 nanospindles (NSs) are about 500 nm long and 50 nm wide. X-ray diffraction (XRD) patterns revealed the successful formation of the ZnO, Fe2O3, and ZnO/Fe2O3 samples and indicated that their crystallite sizes varied from 20 to 29 nm depending on the ZnO : Fe2O3 weight ratio. Ultraviolet-visible (UV-vis) spectra showed that the bandgap energies of ZnO and Fe2O3 were 3.15 eV and 2.1 eV, respectively. Energy dispersive X-ray spectroscopy (EDS) results revealed the successful combination of ZnO and Fe2O3. Photocatalytic activity of the materials was evaluated through the degradation of methylene blue (MB) in aqueous solution under green light-emitting diode (GLED) irradiation. The results indicated that the ZnO/Fe2O3 composite showed a remarkable enhanced degradation capacity compared to bare ZnO NPls and Fe2O3 NSs. The ZnO : Fe2O3 = 3 : 2 sample demonstrated the best performance among all samples under identical conditions with a degradation efficiency of 99.3% for MB after 85 min. The optimum photocatalytic activity of the sample with ZnO : Fe2O3 = 3 : 2 was nearly 3.6% higher than that of the pure ZnO sample and 1.12 times more than that of the pristine Fe2O3 sample. Moreover, the highest photo-degradation was obtained at a photocatalyst dosage of 0.25 g l-1 in dye solution.

Orally Deliverable Iron-Ceria Nanotablets for Treatment of Inflammatory Bowel Disease.

Ceria-based nanoparticles are versatile in treating various inflammatory diseases, but their feasibility in clinical translation is undermined by safety concerns and a limited delivery system. Meanwhile, the idiopathic nature of inflammatory bowel disease (IBD) calls for a wider variety of therapeutics via moderation of the intestinal immune system. In this regard, the synthesis and oral formulation of iron-ceria nanoparticles (CF NPs) with enhanced nanozymic activity and lower toxicity risk than conventional ceria-based nanoparticles are reported. CF NPs are clustered in calcium phosphate (CaP) and coated with a pH-responsive polymer to provide the enteric formulation of iron-ceria nanotablets (CFNT). CFNT exhibits a marked alleviative efficacy in the dextran sodium sulfate (DSS)-induced enterocolitis model in vivo by modulating the pro-inflammatory behavior of innate immune cells including macrophages and neutrophils, promoting anti-inflammatory cytokine profiles, and downregulating key transcription factors of inflammatory pathways.

Musa paradisiaca L. peel extract-bioinspired anisotropic nano-silver with the multipurpose of hydrogenation eco-catalyst and antimicrobial resistance.

In an effort to pursue a green synthesis approach, the biosynthesis of nano-silver (nAg) using plant extracts has garnered significant attention, particularly for its antimicrobial resistance and medical applications, which have been the focus of numerous studies. However, there remains a gap in surface catalytic studies, especially regarding the hydrogenation of 4-nitrophenol. While some studies have addressed catalytic kinetics, thermodynamic aspects have been largely overlooked, leaving the catalytic mechanisms of biosynthesized nAg unclear. In this context, the present work offers a straightforward, eco-friendly, and efficient protocol to obtain nano-silver inspired by Musa paradisiaca L. peel extract. This nAg serves multiple purposes, including antimicrobial resistance and as an eco-catalyst for hydrogenation. Predominantly consisting of zero-valent silver with anisotropic polyhedral shapes, mainly decahedra with an edge length of 50 nm, this nAg demonstrated effective antimicrobial action against both S. aureus and E. coli bacteria. More importantly, both kinetic and thermodynamic studies on the hydrogenation of 4-nitrophenol to 4-aminophenol catalyzed by this bio-inspired nAg revealed that the rate-limiting step is not diffusion-limited. Instead, the adsorbed hydrogen and 4-nitrophenolate react together via electron transfer on the surface of the nAg. The activation energy of 26.24 kJ mol-1 indicates a highly efficient eco-catalyst for such hydrogenation processes.

Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer.

Purpose: In cases where rebiopsy fails to find the epidermal growth factor receptor (EGFR) T790M mutation, the criteria for selecting patients for repeated rebiopsy remains unclear. This study aimed to assess the impact of repeated rebiopsy on T790M mutation detection in non-small cell lung cancer (NSCLC) patients. Methods: Patients with advanced EGFR-mutated NSCLC between January 2018 and December 2021 at three-referral hospitals in South Korea underwent retrospective review. Of 682 patients who had rebiopsy after disease progression, T790M mutation status was assessed in plasma circulating tumor DNA (ctDNA) and/or tumor tissues. Results: The overall T790M positivity rate increased from 40.8% after the first rebiopsy to 52.9% following multiple rebiopsies in the entire study population. Longer duration of initial EGFR TKI use (OR 1.792, ≥8 months vs. <8 months, p=0.004), better EGFR TKI responses (OR 1.611, complete or partial response vs. stable disease, p=0.006), presence of bone metastasis (OR 2.286, p<0.001) were correlated with higher T790M positivity. Longer EGFR TKI use and better responses increased T790M positivity in repeated tissue rebiopsy, while bone metastasis favored liquid rebiopsy. Additionally, T790M status has been shown to be positive over time through repeated rebiopsies ranging from several months to years, suggesting its dynamic nature. Conclusion: In this study, among patients who initially tested negative for T790M in rebiopsy, repeated rebiopsies uncovered an additional 23.5% T790M positivity. Particularly, it is suggested that repeated rebiopsies may be valuable for patients with prolonged EGFR TKI usage, better responses to treatment, and bone metastasis.

Effect of Erector Spinae Plane Block on Postoperative Quality of Recovery in Patients Undergoing Transforaminal or Oblique Lumbar Interbody Fusion: A Randomized Controlled Trial.

BACKGROUND: Erector spinae plane block (ESPB) can has been used for analgesia after lumbar spine surgery. However, its effect on postoperative quality of recovery (QoR) remains underexplored in patients undergoing transforaminal lumbar interbody fusion (TLIF) or oblique lumbar interbody fusion (OLIF). This study hypothesized that ESPB would improve postoperative QoR in this patient cohort. METHODS: Patients undergoing TLIF or OLIF were randomized into ESPB (n=38) and control groups (n=38). In the ESPB group, 25 mL of 0.375% bupivacaine was injected into each erector spinae plane at the T12 level under ultrasound guidance before skin incision. Multimodal analgesia, including wound infiltration, was applied in both groups. The QoR-15 score was measured before surgery and 1 day (primary outcome) and 3 days after surgery. Postoperative pain at rest and during ambulation and postoperative ambulation were also evaluated for 3 days after surgery. RESULTS: Perioperative QoR-15 scores were not significantly different between the ESPB and control groups including at 1 day after surgery (80±28 vs. 81±25, respectively; P=0.897). Patients in the ESPB group had a significantly lower mean (±SD) pain score during ambulation 1 hour after surgery (7±3 vs. 9±1, respectively; P=0.013) and significantly shorter median (interquartile range) time to the first ambulation after surgery (2.0 [1.0 to 5.5] h vs. 5.0 [1.8 to 10.0] h, respectively; P=0.038). There were no between-group differences in pain scores at other times or in the cumulative number of postoperative ambulations. CONCLUSION: ESPB, as performed in this study, did not improve the QoR after TLIF or OLIF with multimodal analgesia.

Pathogenicity of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Cats in Mice and Ferrets, South Korea, 2023.

The prevalence of highly pathogenic avian influenza (HPAI) A(H5N1) viruses has increased in wild birds and poultry worldwide, and concomitant outbreaks in mammals have occurred. During 2023, outbreaks of HPAI H5N1 virus infections were reported in cats in South Korea. The H5N1 clade 2.3.4.4b viruses isolated from 2 cats harbored mutations in the polymerase basic protein 2 gene encoding single amino acid substitutions E627K or D701N, which are associated with virus adaptation in mammals. Hence, we analyzed the pathogenicity and transmission of the cat-derived H5N1 viruses in other mammals. Both isolates caused fatal infections in mice and ferrets. We observed contact infections between ferrets, confirming the viruses had high pathogenicity and transmission in mammals. Most HPAI H5N1 virus infections in humans have occurred through direct contact with poultry or a contaminated environment. Therefore, One Health surveillance of mammals, wild birds, and poultry is needed to prevent potential zoonotic threats.

Association Between Body Mass Index Changes and All-Cause Mortality in Parkinson's Disease.

Background: Whether body weight changes are associated with Parkinson's disease (PD) mortality remains uncertain. Objective: To investigate the association between changes in body mass index (BMI) and all-cause mortality in patients with PD. Methods: This nationwide cohort study enrolled 20,703 individuals with new-onset PD (ICD-10 code: G20 and a rare intractable disease registration code: V124) who underwent health screening program by the Korean National Health Insurance Service within two years from pre- and post-PD diagnosis. We identified nine BMI change groups based on three BMI status: underweight (BMI <  18.5 kg/m2), normal or overweight (18.5 kg/m2≤BMI <  25 kg/m2), and obese (BMI≥25 kg/m2). Results: Of 20,703 individuals, 3,789 (18.0%) died during the follow-up period. Excessive weight loss to underweight in the obese group (hazard ratio [HR] = 3.36, 95% CI:1.60-7.08), weight loss in the normal to overweight group (HR = 2.04, 95% CI:1.75-2.39), sustained underweight status (HR = 2.05, 95% CI:1.67-2.52), and weight gain from underweight to normal or overweight (HR = 1.52, 95% CI:1.15-2.02) were associated with increased mortality. Sustained obese status (HR = 0.80, 95% CI:0.74-0.87) and weight gain in the normal to overweight group (HR = 0.82, 95% CI:0.71-0.95) were associated with reduced mortality. Conclusions: We found that BMI change at diagnosis was associated with mortality in patients with PD. Specifically, being underweight either before or after diagnosis as well as experiencing weight loss, were associated with increased mortality. These findings provide valuable insights for weight management planning in PD, highlighting the importance of individualized approach that consider pre-diagnosis BMI.

Whether body weight changes are associated with Parkinson's disease (PD) mortality remains uncertain. This study looked at how changes in body weight affect the chances of survival in people who have recently been diagnosed with PD. We followed 20,703 individuals who were newly diagnosed with this condition and checked their weight changes before and after their diagnosis. We found that people with PD who lost a lot of weight to become underweight had a higher risk of dying during our study. Similarly, those who were already underweight and remained so also had a higher mortality risk. On the other hand, people who maintained a weight or gained a small amount of weight after their diagnosis had the lowest risk of dying. Our research found that weight changes at diagnosis were associated with mortality in PD, with underweight or weight loss being linked to increased risk of death. Each person's situation is different, so weight management should be tailored to each individual, considering their weight before they were diagnosed with PD.

Ethnic differences in the prevalence of amyloid positivity and cognitive trajectories.

INTRODUCTION: We investigated the prevalence of amyloid beta (Aß) positivity (+) and cognitive trajectories in Koreans and non-Hispanic Whites (NHWs). METHODS: We included 5121 Koreans from multiple centers across South Korea and 929 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent Aß positron emission tomography and were categorized into cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia stages. Age, sex, education, and apolipoprotein E. genotype were adjusted using multivariable logistic regression and stabilized inverse probability of treatment weights based on the propensity scores to mitigate imbalances in these variables. RESULTS: The prevalence of Aß+ was lower in CU Koreans than in CU NHWs (adjusted odds ratio 0.60). Aß+ Koreans showed a faster cognitive decline than Aß+ NHWs in the CU (B = -0.314, p = .004) and MCI stages (B = -0.385, p < .001). DISCUSSION: Ethnic characteristics of Aß biomarkers should be considered in research and clinical application of Aß-targeted therapies in diverse populations. HIGHLIGHTS: Koreans have a lower prevalence of Aß positivity compared to NHWs in the CU stage. The effects of Alzheimer's risk factors on Aß positivity differ between Koreans and NHWs. Aß-positive (Aß+) Koreans show faster cognitive decline than Aß+ NHWs in the CU and MCI stages.

Incorporation of Whole-Body Metabolic Tumor Burden into Current Prognostic Models for Non-Small Cell Lung Cancer patients with Spine metastasis.

BACKGROUND CONTEXT: Numerous prognostic models are utilized for surgical decision and prognostication in metastatic spine tumors. However, these models often fail to consider the whole-body tumor burden into account, which may be crucial for the prognosis of metastatic cancers. A potential surrogate marker for tumor burden, whole-body metabolic tumor burden (wMTB), can be calculated from total lesion glycolysis (TLG) obtained from 18F-Fludeoxyglucose positive emission tomography (18F-FDG PET) images. PURPOSE: We aimed to improve prognostic power of current models by incorporating wMTB for non-small cell lung cancer (NSCLC) patients with spine metastases. DESIGN: Retrospective analysis using a review of electrical medical records and survival data. PATIENT SAMPLE: In this study, we included 74 NSCLC patients with image proven spine metastases. OUTCOME MEASURES: Increase in Integrated Discrimination Improvement (IDI) index after incorporation of wMTB into prognostic scores. METHODS: Enrolled patients' baseline data, cancer characteristics and survival status were retrospectively collected. Five widely used prognostic scores (Tomita, Katagiri, Tokuhashi, Global Spine Tumor Study Group [GSTSG], New England Spine Metastasis Score [NESMS]), and TLG indexes were calculated for all patients. The relationships among survival time, prognostic models and TLG values were analyzed. Improvement of prognostic power was validated by incorporating significant TLG index into significant current models. RESULTS: Among current prognostic models, Tomita (EGFR wild-type), Katagiri, GSTSG and Tokuhashi were significantly related to patient survival. Among TLG indexes, LogTLG3 was significantly related to survival. Incorporation of LogTLG3 into significant prognostic models resulted in positive IDI index until three years in all models. CONCLUSION: This study showed that incorporation of wMTB improved prognostic power of current prognostic models of metastatic spine tumors.

Rapid and efficient dual detection of Zn2+ ions and oxytetracycline hydrochloride using a responsive fluorescent "on-off" sensor based on simple salen-type Schiff base ligand.

This research has progressed a effective dual detection chemosensor of zinc ion and oxytetracycline hydrochloride antibiotic based on fluorescence technique. A straightforward method utilizing microwave irradiation was employed to synthesize the salen-type Schiff base ligand N,N'-bis(salicylaldehyde)4,5-dichloro-1,2-phenylenediamine (H2I), providing a good 70% yield. In ethanol, the H2I sensor demonstrated remarkable rapidity, selectivity, and sensitivity in detecting zinc ions. The fluorescence spectrum exhibited a 44-fold substantial enhancement at 522 nm and achieved a low limit of detection (LOD) of 1.47 µM. The ability to recognize zinc ions in different real water samples demonstrated from 98.67% to 103.31% in recovery. Interestingly, a naked-eye visible fluorescence color of H2I solution impregnated filter papers turned colorless into yellow under UV irradiation by adding Zn2+ ion, renders it suitable for developing a practical zinc ion detection kit test. In particular, the I-Zn2+ complex effectively quenched the fluorescence toward oxytetracycline hydrochloride (OTC) with a LOD value of 1.49×10-2 µM in DMSO: H2O (6:4, v/v). This is a novel and effective procedure in sensing OTC antibiotic by the I-Zn2+ complex. These findings hold immense potential for the development of dual fluorescent probes, thereby enhancing sensitivity and specificity in identifying metal ions and antibiotics in wide range of applications.

Deep learning-based predictive models for forex market trends: Practical implementation and performance evaluation.

In recent years, there has been growing interest in the prediction of financial market trends, due to its potential applications in the real world. Unlike traditional investment avenues such as the stock market, the foreign exchange (Forex) market revolves around two primary types of orders that correspond with the market's direction: upward and downward. Consequently, forecasting the behaviour of the Forex behaviour market can be simplified into a binary classification problem to streamline its complexity. Despite the significant enhancements and improvements in performance seen in recent proposed predictive models for the forex market, driven by the advancement of deep learning in various domains, it remains imperative to approach these models with careful consideration of best practices and real-world applications. Currently, only a limited number of papers have been dedicated to this area. This article aims to bridge this gap by proposing a practical implementation of deep learning-based predictive models that perform well for real-world trading activities. These predictive mechanisms can help traders in minimising budget losses and anticipate future risks. Furthermore, the paper emphasises the importance of focussing on return profit as the evaluation metric, rather than accuracy. Extensive experimental studies conducted on realistic Yahoo Finance data sets validate the effectiveness of our implemented prediction mechanisms. Furthermore, empirical evidence suggests that employing the use of three-value labels yields superior accuracy performance compared to traditional two-value labels, as it helps reduce the number of orders placed.

Biophysically stressed vascular smooth muscle cells express MCP-1 via a PDGFR-ß-HMGB1 signaling pathway.

Vascular smooth muscle cells (VSMCs) under biophysical stress play an active role in the progression of vascular inflammation, but the precise mechanisms are unclear. This study examined the cellular expression of monocyte chemoattractant protein 1 (MCP-1) and its related mechanisms using cultured rat aortic VSMCs stimulated with mechanical stretch (MS, equibiaxial cyclic stretch, 60 cycles/ min). When the cells were stimulated with 10% MS, MCP-1 expression was markedly increased compared to those in the cells stimulated with low MS intensity (3% or 5%). An enzyme-linked immunosorbent assay revealed an increase in HMGB1 released into culture media from the cells stimulated with 10% MS compared to those stimulated with 3% MS. A pretreatment with glycyrrhizin, a HMGB1 inhibitor, resulted in the marked attenuation of MCP-1 expression in the cells stimulated with 10% MS, suggesting a key role of HMGB1 on MCP-1 expression. Western blot analysis revealed higher PDGFR-α and PDGFR-ß expression in the cells stimulated with 10% MS than 3% MS-stimulated cells. In the cells deficient of PDGFR-ß using siRNA, but not PDGFR-α, HMGB1 released into culture media was significantly attenuated in the 10% MS-stimulated cells. Similarly, MCP-1 expression induced in 10% MS-stimulated cells was also attenuated in cells deficient of PDGFR-ß. Overall, the PDGFR-ß signaling plays a pivotal role in the increased expression of MCP-1 in VSMCs stressed with 10% MS. Therefore, targeting PDGFR-ß signaling in VSMCs might be a promising therapeutic strategy for vascular complications in the vasculatures under excessive biophysical stress.

Targeting ROS-sensing Nrf2 potentiates anti-tumor immunity of intratumoral CD8+ T and CAR-T cells.

Cytotoxic T lymphocytes (CTLs) play a crucial role in cancer rejection. However, CTLs encounter dysfunction and exhaustion in the immunosuppressive tumor microenvironment (TME). Although the reactive oxygen species (ROS)-rich TME attenuates CTL function, the underlying molecular mechanism remains poorly understood. The nuclear factor erythroid 2-related 2 (Nrf2) is the ROS-responsible factor implicated in increasing susceptibility to cancer progression. Therefore, we examined how Nrf2 is involved in anti-tumor responses of CD8+ T and chimeric antigen receptor (CAR) T cells in the ROS-rich TME. Here, we demonstrated that tumor growth in Nrf2-/- mice was significantly controlled and was reversed by T cell depletion and further confirmed that Nrf2 deficiency in T cells promotes anti-tumor responses using an adoptive transfer model of antigen-specific CD8+ T cells. Nrf2-deficient CTLs are resistant to ROS, and their effector functions are sustained in the TME. Furthermore, Nrf2 knockdown in human CAR-T cells enhanced the survival and function of intratumoral CAR-T cells in a solid tumor xenograft model and effectively controlled tumor growth. ROS-sensing Nrf2 inhibits the anti-tumor T cell responses, indicating that Nrf2 may be a potential target for T cell immunotherapy strategies against solid tumors.

Automated identification of thrombectomy amenable vessel occlusion on computed tomography angiography using deep learning.

Introduction: We developed and externally validated a fully automated algorithm using deep learning to detect large vessel occlusion (LVO) in computed tomography angiography (CTA). Method: A total of 2,045 patients with acute ischemic stroke who underwent CTA were included in the development of our model. We validated the algorithm using two separate external datasets: one with 64 patients (external 1) and another with 313 patients (external 2), with ischemic stroke. In the context of current clinical practice, thrombectomy amenable vessel occlusion (TAVO) was defined as an occlusion in the intracranial internal carotid artery (ICA), or in the M1 or M2 segment of the middle cerebral artery (MCA). We employed the U-Net for vessel segmentation on the maximum intensity projection images, followed by the application of the EfficientNetV2 to predict TAVO. The algorithm's diagnostic performance was evaluated by calculating the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: The mean age in the training and validation dataset was 68.7 ± 12.6; 56.3% of participants were men, and 18.0% had TAVO. The algorithm achieved AUC of 0.950 (95% CI, 0.915-0.971) in the internal test. For the external datasets 1 and 2, the AUCs were 0.970 (0.897-0.997) and 0.971 (0.924-0.990), respectively. With a fixed sensitivity of 0.900, the specificities and PPVs for the internal test, external test 1, and external test 2 were 0.891, 0.796, and 0.930, and 0.665, 0.583, and 0.667, respectively. The algorithm demonstrated a sensitivity and specificity of approximately 0.95 in both internal and external datasets, specifically for cases involving intracranial ICA or M1-MCA occlusion. However, the diagnostic performance was somewhat reduced for isolated M2-MCA occlusion; the AUC for the internal and combined external datasets were 0.903 (0.812-0.944) and 0.916 (0.816-0.963), respectively. Conclusion: We developed and externally validated a fully automated algorithm that identifies TAVO. Further research is needed to evaluate its effectiveness in real-world clinical settings. This validated algorithm has the potential to assist early-career physicians, thereby streamlining the treatment process for patients who can benefit from endovascular treatment.