Incidence of Carotid Blowout Syndrome in Patients with Head and Neck Cancer after Radiation Therapy: A Cohort Study.

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan-Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3-7%) after both surgery and RT, 4% (95% CI = 2-6%) after surgery alone, and 5% (95% CI = 3-7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

Isoxanthohumol reduces neointimal hyperplasia through the apelin/AKT pathway.

The abnormal proliferation, migration, and inflammation of vascular smooth muscle cells (VSMCs) play crucial roles in the development of neointimal hyperplasia and restenosis. Exposure to inflammatory cytokines such as platelet-derived growth factor (PDGF)-BB and tumour necrosis factor-alpha (TNF-α) induces the transformation of contractile VSMCs into abnormal synthetic VSMCs. Isoxanthohumol (IXN) has significant anti-inflammatory, antiproliferative, and antimigratory effects. This study aimed to explore the therapeutic impact and regulatory mechanism of IXN in treating neointimal hyperplasia. The present findings indicate that IXN effectively hinders the abnormal proliferation, migration, and inflammation of VSMCs triggered by PDGF or TNF-α. This inhibition is primarily achieved through the modulation of the apelin/AKT or AKT pathway, respectively. In an in vivo model, IXN effectively reduced neointimal hyperplasia in denuded femoral arteries. These results suggest that IXN holds promise as a potential and innovative therapeutic candidate for the treatment of restenosis.

Differential clustering of visual and choice- and saccade-related activity in macaque V3A and CIP.

Neurons in sensory and motor cortices tend to aggregate in clusters with similar functional properties. Within the primate dorsal ("where") pathway, an important interface between three-dimensional (3-D) visual processing and motor-related functions consists of two hierarchically organized areas: V3A and the caudal intraparietal (CIP) area. In these areas, 3-D visual information, choice-related activity, and saccade-related activity converge, often at the single-neuron level. Characterizing the clustering of functional properties in areas with mixed selectivity, such as these, may help reveal organizational principles that support sensorimotor transformations. Here we quantified the clustering of visual feature selectivity, choice-related activity, and saccade-related activity by performing correlational and parametric comparisons of the responses of well-isolated, simultaneously recorded neurons in macaque monkeys. Each functional domain showed statistically significant clustering in both areas. However, there were also domain-specific differences in the strength of clustering across the areas. Visual feature selectivity and saccade-related activity were more strongly clustered in V3A than in CIP. In contrast, choice-related activity was more strongly clustered in CIP than in V3A. These differences in clustering may reflect the areas' roles in sensorimotor processing. Stronger clustering of visual and saccade-related activity in V3A may reflect a greater role in within-domain processing, as opposed to cross-domain synthesis. In contrast, stronger clustering of choice-related activity in CIP may reflect a greater role in synthesizing information across functional domains to bridge perception and action.NEW & NOTEWORTHY The occipital and parietal cortices of macaque monkeys are bridged by hierarchically organized areas V3A and CIP. These areas support 3-D visual transformations, carry choice-related activity during 3-D perceptual tasks, and possess saccade-related activity. This study quantifies the functional clustering of neuronal response properties within V3A and CIP for each of these domains. The findings reveal domain-specific cross-area differences in clustering that may reflect the areas' roles in sensorimotor processing.

Nε-(1-Carboxymethyl)-L-lysine/RAGE Signaling Drives Metastasis and Cancer Stemness through ERK/NFκB axis in Osteosarcoma.

Osteosarcoma is an extremely aggressive bone cancer with poor prognosis. Nε-(1-Carboxymethyl)-L-lysine (CML), an advanced glycation end product (AGE), can link to cancer progression, tumorigenesis and metastasis, although the underlying mechanism remains unclear. The role of CML in osteosarcoma progression is still unclear. We hypothesized that CML could promote migration, invasion, and stemness in osteosarcoma cells. CML and its receptor (RAGE; receptor for AGE) were higher expressed at advanced stages in human osteosarcoma tissues. In mouse models, which streptozotocin was administered to induce CML accumulation in the body, the subcutaneous tumor growth was not affected, but the tumor metastasis using tail vein injection model was enhanced. In cell models (MG63 and U2OS cells), CML enhanced tumor sphere formation and acquisition of cancer stem cell characteristics, induced migration and invasion abilities, as well as triggered the epithelial-mesenchymal transition process, which were associated with RAGE expression and activation of downstream signaling pathways, especially the ERK/NFκB pathway. RAGE inhibition elicited CML-induced cell migration, invasion, and stemness through RAGE-mediated ERK/NFκB pathway. These results revealed a crucial role for CML in driving stemness and metastasis in osteosarcoma. These findings uncover a potential CML/RAGE connection and mechanism to osteosarcoma progression and set the stage for further investigation.

Inhibition of Indoxyl Sulfate-Induced Reactive Oxygen Species-Related Ferroptosis Alleviates Renal Cell Injury In Vitro and Chronic Kidney Disease Progression In Vivo.

The accumulation of the uremic toxin indoxyl sulfate (IS) is a key pathological feature of chronic kidney disease (CKD). The effect of IS on ferroptosis and the role of IS-related ferroptosis in CKD are not well understood. We used a renal tubular cell model and an adenine-induced CKD mouse model to explore whether IS induces ferroptosis and injury and affects iron metabolism in the renal cells and the kidneys. Our results showed that exposure to IS induced several characteristics for ferroptosis, including iron accumulation, an impaired antioxidant system, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. Exposure to IS triggered intracellular iron accumulation by upregulating transferrin and transferrin receptors, which are involved in cellular iron uptake. We also observed increased levels of the iron storage protein ferritin. The effects of IS-induced ROS generation, lipid peroxidation, ferroptosis, senescence, ER stress, and injury/fibrosis were effectively alleviated by treatments with an iron chelator deferoxamine (DFO) in vitro and the adsorbent charcoal AST-120 (scavenging the IS precursor) in vivo. Our findings suggest that IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys. AST-120 administration may serve as a potential therapeutic strategy.

Toughening of epoxy thermosets by self-assembled nanostructures of amphiphilic comb-like random copolymers.

Amphiphilic comb-like random copolymers synthesized from poly(ethylene glycol) methyl ether methacrylate (PEGMMA) and stearyl methacrylate (SMA) with PEGMMA contents ranging between 30 wt% and 25 wt% were demonstrated to self-assemble into various well-defined nanostructures, including spherical micelles, wormlike micelles, and vesicle-like nanodomains, in anhydride-cured epoxy thermosets. In addition, the polymer blends of the comb-like random copolymer and poly(stearyl methacrylate) were prepared and incorporated into epoxy thermosets to form irregularly shaped nanodomains. Our research findings indicate that both the comb-like random copolymers and polymer blends are suitable as toughening modifiers for epoxy. When added at a concentration of 5 wt%, both types of modifiers lead to substantial improvements in the tensile toughness (>289%) and fracture toughness of epoxy thermosets, with minor reductions in their elastic modulus (<16%) and glass transition temperature (<6.1 °C). The fracture toughness evaluated in terms of the critical stress intensity factor (KIC) and the strain energy release rate (GIC) increased by more than 67% and 131% for the modified epoxy thermosets containing comb-like random copolymers.

Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers.

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Comprehensive Investigation of Constant Voltage Stress Time-Dependent Breakdown and Cycle-to-Breakdown Reliability in Y-Doped and Si-Doped HfO2 Metal-Ferroelectric-Metal Memory.

In this study, we comprehensively investigate the constant voltage stress (CVS) time-dependent breakdown and cycle-to-breakdown while considering metal-ferroelectric-metal (MFM) memory, which has distinct domain sizes induced by different doping species, i.e., Yttrium (Y) (Sample A) and Silicon (Si) (Sample B). Firstly, Y-doped and Si-doped HfO2 MFM devices exhibit domain sizes of 5.64 nm and 12.47 nm, respectively. Secondly, Si-doped HfO2 MFM devices (Sample B) have better CVS time-dependent breakdown and cycle-to-breakdown stability than Y-doped HfO2 MFM devices (Sample A). Therefore, a larger domain size showing higher extrapolated voltage under CVS time-dependent breakdown and cycle-to-breakdown evaluations was observed, indicating that the domain size crucially impacts the stability of MFM memory.

PEMT rs7946 Polymorphism and Sex Modify the Effect of Adequate Dietary Choline Intake on the Risk of Hepatic Steatosis in Older Patients with Metabolic Disorders.

In humans, PEMT rs7946 polymorphism exerts sex-specific effects on choline requirement and hepatic steatosis (HS) risk. Few studies have explored the interaction effect of the PEMT rs7946 polymorphism and sex on the effect of adequate choline intake on HS risk. In this cross-sectional study, we investigated the association between PEMT polymorphism and adequate choline intake on HS risk. We enrolled 250 older patients with metabolic disorders with (n = 152) or without (n = 98; control) ultrasonically diagnosed HS. An elevated PEMT rs7946 A allele level was associated with a lower HS risk and body mass index in both men and women. Dietary choline intake-assessed using a semiquantitative food frequency questionnaire-was associated with reduced obesity in men only (p for trend < 0.05). ROC curve analysis revealed that the cutoff value of energy-adjusted choline intake for HS diagnosis was 448 mg/day in women (AUC: 0.62; 95% CI: 0.57-0.77) and 424 mg/day in men (AUC: 0.63, 95% CI: 0.57-0.76). In women, GG genotype and high choline intake (>448 mg/day) were associated with a 79% reduction in HS risk (adjusted OR: 0.21; 95% CI: 0.05-0.82); notably, GA or AA genotype was associated with a reduced HS risk regardless of choline intake (p < 0.05). In men, GG genotype and high choline intake (>424 mg/day) were associated with a 3.7-fold increase in HS risk (OR: 3.7; 95% CI: 1.19-11.9). Further adjustments for a high-density lipoprotein level and body mass index mitigated the effect of choline intake on HS risk. Current dietary choline intake may be inadequate for minimizing HS risk in postmenopausal Taiwanese women carrying the PEMT rs7946 GG genotype. Older men consuming more than the recommended amount of choline may have an increased risk of nonalcoholic fatty liver disease; this risk is mediated by a high-density lipoprotein level and obesity.

Nε-(1-Carboxymethyl)-L-lysine, an advanced glycation end product, exerts malignancy on chondrosarcoma via the activation of cancer stemness.

Despite epidemiological evidence that suggests diabetes mellitus is a risk factor for cancer, the link between diabetes mellitus and primary bone cancer is rarely discussed. Chondrosarcomas are primary malignant cartilage tumors with poor prognosis and high metastatic potential. It remains unclear whether hyperglycemia affects the stemness and malignancy of chondrosarcoma cells. Nε-(1-Carboxymethyl)-L-lysine (CML), an advanced glycation end product (AGE), is a major immunological epitope detected in the tissue proteins of diabetic patients. We hypothesized that CML could enhance cancer stemness in chondrosarcoma cells. CML enhanced tumor-sphere formation and the expression of cancer stem cell markers in human chondrosarcoma cell lines. Migration and invasion ability and the epithelial-mesenchymal transition (EMT) process were also induced by CML treatment. Moreover, CML increased the protein expression levels of the receptor for AGE (RAGE), phosphorylated NFκB-p65, and decreased the phosphorylation of AKT and GSK-3. We also found that hyperglycemia with high CML levels facilitated tumor metastasis, whereas tumor growth was not affected in the streptozotocin (STZ)-induced diabetic NOD/SCID tumor xenograft mouse models. Our results indicate that CML enhances chondrosarcoma stemness and metastasis, which may reveal the relationship between AGE and bone cancer metastasis.

Resveratrol Alleviates Advanced Glycation End-Products-Related Renal Dysfunction in D-Galactose-Induced Aging Mice.

The elderly have higher concentrations of advanced glycation end-products (AGEs). AGEs are considered risk factors that accelerate aging and cause diabetic nephropathy. The effects of AGEs on renal function in the elderly remain to be clarified. This study aimed to explore the role of AGEs in renal function decline in the elderly and the protective effect of resveratrol, a stilbenoid polyphenol, comparing it with aminoguanidine (an AGEs inhibitor). A D-galactose-induced aging mouse model was used to explore the role of AGEs in the process of renal aging. The mice were administered D-galactose subcutaneously for eight weeks in the presence or absence of orally administered aminoguanidine or resveratrol. The results showed that the serum levels of AGEs and renal function markers BUN, creatinine, and cystatin C in the mice significantly increased after the administration of D-galactose, and this outcome could be significantly reversed by treatment with aminoguanidine or resveratrol. The protein expression levels for apoptosis, fibrosis, and aging-related indicators in the kidneys were significantly increased, which could also be reversed by treatment with aminoguanidine or resveratrol. These findings suggest that resveratrol could alleviate AGEs-related renal dysfunction through the improvement of renal cellular senescence, apoptosis, and fibrosis in D-galactose-induced aging in mice.

Neuronal Representations Supporting Three-Dimensional Vision in Nonhuman Primates.

The visual system must reconstruct the dynamic, three-dimensional (3D) world from ambiguous two-dimensional (2D) retinal images. In this review, we synthesize current literature on how the visual system of nonhuman primates performs this transformation through multiple channels within the classically defined dorsal (where) and ventral (what) pathways. Each of these channels is specialized for processing different 3D features (e.g., the shape, orientation, or motion of objects, or the larger scene structure). Despite the common goal of 3D reconstruction, neurocomputational differences between the channels impose distinct information-limiting constraints on perception. Convergent evidence further points to the little-studied area V3A as a potential branchpoint from which multiple 3D-fugal processing channels diverge. We speculate that the expansion of V3A in humans may have supported the emergence of advanced 3D spatial reasoning skills. Lastly, we discuss future directions for exploring 3D information transmission across brain areas and experimental approaches that can further advance the understanding of 3D vision.

Comparison of the synthesis and biological properties of no-carrier-added and carrier-added 4-borono-2-[18F]fluorophenylalanine ([18F]FBPA).

PURPOSE: Boron neutron capture therapy (BNCT), an attractive strategy for cancer treatment, can kill tumor cells and avoid injury to surrounding healthy cells. 4-Borono-2-[18F]fluorophenylalanine ([18F]FBPA) positron emission tomography (PET) is a reliable tool for patient screening. Due to the relatively low radiochemical yield when employing the electrophilic route, this study was able to develop a new method to produce no-carrier-added (NCA) [18F]FBPA and compare the biological characteristics with carrier-added (CA) characteristics. PROCEDURES: By starting from 4-bromo-2-nitrobenzaldehyde, NCA [18F]FBPA was prepared using radiofluorination, alkylation, borylation, and hydrolysis. Cellular uptake analyses, microPET imaging, and biodistribution analyses were conducted to characterize the biological properties of NCA and CA [18F]FBPA. RESULTS: The radiochemical yield of NCA [18F]FBPA was 20 % ± 6 % (decay corrected) with a radiochemical purity of >98 % and molar activity of 56 ± 15 GBq/µmol in a 100-min synthesis. The in vitro accumulation was significantly higher for NCA [18F]FBPA than for CA [18F]FBPA in both SAS and CT-26 cells. However, no apparent differences in tumor uptake were observed between NCA and CA [18F]FBPA-injected tumor-bearing mice. CONCLUSIONS: We successfully prepared NCA [18F]FBPA through nucleophilic substitution and achieved improved radiochemical yield and purity. We also demonstrated the effects of the amount of nonradioactive FBPA on in vitro cellular uptake and in vivo imaging studies.

In vitro genotoxicity assessment and 28-day repeated dose oral toxicity study of steady-calcium formula in rats.

Steady-calcium formula (SCF), a functional food mixture with potential of joint care, contains five major ingredients. However, the uncertain cross-reactivity among these included ingredients cannot be excluded. Hence, it is important to ensure the safety of this mixture. In this study, the safety of SCF was evaluated through in vitro genotoxicity assessment and 28-day oral toxicity study in rats. The bacterial reverse mutation test and mammalian chromosome aberration test displayed that SCF did not induce mutagenicity and clastogenicity. The 28-day repeated dose assessment of SCF in rats revealed no mortality and adverse effects in clinical signs, body weight, urinalysis, hematology, organ weight, and histopathology at all treated groups. Although some significant changes were observed in food intake and parameters of serum biochemistry at the highest dose in males, they were not dose-related and considered to be within normal range. These findings indicate that SCF does not possess genotoxic potential and no obvious evidence of subacute toxicity. These results demonstrate for the first time that the genotoxicity and subacute toxicity for SCF are negative under our experimental conditions and the no observed adverse effect level (NOAEL) of SCF may be defined as at least 5470 mg/kg/day.

Mediating roles of leukoaraiosis and infarcts in the effects of unilateral carotid artery stenosis on cognition.

Background and objectives: Leukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains. Materials and methods: One hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (<50%) were recruited. The PVL, DWML, and infarct severity were visually rated on MRI. A comprehensive cognitive battery was administered and standardized based on age norms. Correlation and mediation analyses were adopted to examine the direct and indirect influence of CAS, leukoaraiosis, and infarct on specific cognitive domains with adjustment for education, hypertension, diabetes mellitus, and hyperlipidemia. Results: Carotid artery stenosis severity was associated with ipsilateral leukoaraiosis and infarct. Left CAS had direct effects on most cognitive domains, except for visual memory and constructional ability, and transmitted its indirect effects on all cognitive domains through ipsilateral PVL, and on constructional ability and psychomotor through infarcts. Right CAS only had negative direct effects on visual memory, psychomotor, design fluency and color processing speed, and transmitted its indirect effects on visual memory, word and color processing speed through ipsilateral infarcts. The trends of direct and indirect cognitive effects remained similar after covariate adjustment. Conclusion: Left and right CAS would predominantly lead to verbal and non-verbal cognitive impairment respectively, and such effects could be mediated through CAS-related leukoaraiosis and infarct. Given that cognition is subject to heterogeneous pathologies, the exact relationships between markers of large and small vessel diseases and their composite prognostic effects on cognition requires further investigation.

Barriers to depression care among middle-aged and older adults in Taiwan's universal healthcare system.

Background: Barriers to depression care differ across countries, highlighting the importance of identifying gaps in health-service coverage for regional health systems. This study aims to identify the bottlenecks of depression care and associated factors. Methods: We used data from the Taiwan Longitudinal Study on Aging of 2015, included 7675 participants aged 50 years and older. We identified participants with clinically relevant depression using the Center for Epidemiological Studies Depression Scale or Taiwan's National Health Insurance program claims records of depressive disorders. Bottleneck analysis was based on a modified Tanahashi framework with four stages: healthcare accessibility, initial contact, adequate treatment, and effective coverage. Individual factors associated with achieving these stages were estimated using multivariable logistic regression models with multiple imputation. Findings: We identified 1253 patients with clinically relevant depression; 83% perceived it as convenient to access healthcare, but only 27% had initial contact with health services, 16% received adequate coverage, and 11% achieved effective treatment. In terms of factors associated with initial contact, being female, married, or retired/unemployed; having a high education level, social group engagement, or self-reported diabetes mellitus; exercising regularly; and participating in social leisure activities were associated with increasing contact. Those with alcohol use had a low likelihood of treatment. Interpretation: Initial contact constitutes the primary bottleneck of depression care in Taiwan. Improving mental health literacy and enhancing depression screening would be helpful to elevate treatment rates and improve depression care. Funding: This study was supported by a grant from the Ministry of Health and Welfare, Taiwan.

Automatic identification of early ischemic lesions on non-contrast CT with deep learning approach.

Early ischemic lesion on non-contrast computed tomogram (NCCT) in acute stroke can be subtle and need confirmation with magnetic resonance (MR) image for treatment decision-making. We retrospectively included the NCCT slices of 129 normal subjects and 546 ischemic stroke patients (onset < 12 h) with corresponding MR slices as reference standard from a prospective registry of Chang Gung Research Databank. In model selection, NCCT slices were preprocessed and fed into five different pre-trained convolutional neural network (CNN) models including Visual Geometry Group 16 (VGG16), Residual Networks 50, Inception-ResNet-v2, Inception-v3, and Inception-v4. In model derivation, the customized-VGG16 model could achieve an accuracy of 0.83, sensitivity 0.85, F-score 0.80, specificity 0.82, and AP 0.82 after using a tenfold cross-validation method, outperforming the pre-trained VGG16 model. In model evaluation, the customized-VGG16 model could correctly identify 53 in 58 subjects (91.37%) including 29 ischemic stroke patients and 24 normal subjects and reached the sensitivity of 86.95% in identifying ischemic NCCT slices (200/230), irrespective of supratentorial or infratentorial lesions. The customized-VGG16 CNN model can successfully identify the presence of early ischemic lesions on NCCT slices using the concept of automatic feature learning. Further study will be proceeded to detect the location of ischemic lesion.

An Overview of Laser Metal Deposition for Cladding: Defect Formation Mechanisms, Defect Suppression Methods and Performance Improvements of Laser-Cladded Layers.

With the development of society and the economy, there is an increasing demand for surface treatment techniques that can efficiently utilize metal materials to obtain good performances in the fields of mechanical engineering and the aerospace industry. The laser metal deposition (LMD) technique for cladding has become a research focus in recent years because of its lower dilution rate, small heat-effect zone and good metallurgical bonding between the coating and substrate. This paper reviews the simulation technology for the melt pool's grain growth mechanism, temperature and stress distribution that are directly related to defect formation in LMD technology. At the same time, the defect suppression method and the performance improvement method of the cladded layer in LMD technology are introduced. Finally, it is pointed out that the active selection of materials according to the required performance, combined with the controllable processing technology, to form the corresponding microstructure, and finally, to actively realize the expected function, is the future development direction of LMD technology.