Search

BACKGROUND: Although changes in diffusion characteristics of the brain parenchyma in neurological disorders are widely studied and used in clinical practice, the change in diffusivity in the cerebrospinal fluid (CSF) system is rarely reported. In this study, free water diffusion in the subarachnoid cisterns and ventricles of the rat brain was examined using diffusion magnetic resonance imaging (MRI), and the effects of neurological disorders on diffusivity in CSF system were investigated. METHODS: Diffusion MRI and T(2)-weighted images were obtained in the intact rats, 24 h after ischemic stroke, and 50 days after mild traumatic brain injury (mTBI). We conducted the assessment of diffusivity in the rat brain in the subarachnoid cisterns around the midbrain, as well as the lateral ventricles. One-way ANOVA and Kruskal–Wallis test were used to evaluate the change in mean diffusivity (MD) and MD histogram, respectively, in CSF system following different neurological disease. RESULTS: A significant decrease in the mean MD value of the subarachnoid cisterns was observed in the stroke rats compared with the intact and mTBI rats (p

Table S1 Full list of included TCIA glioma subjects for the training of the machine-learning models (KPS = Karnofsky Performance Scale) Table S2 MRI data integrity of the training dataset Table S3 Full list of included subjects as an independent validation dataset Table S4 The formulae for the calculation of primary radiomic features.

Purpose: The new classification announced by the World Health Organization in 2016 recognized five molecular subtypes of diffuse gliomas based on isocitrate dehydrogenase (IDH) and 1p/19q genotypes in addition to histologic phenotypes. We aim to determine whether clinical MRI can stratify these molecular subtypes to benefit the diagnosis and monitoring of gliomas.Experimental Design: The data from 456 subjects with gliomas were obtained from The Cancer Imaging Archive. Overall, 214 subjects, including 106 cases of glioblastomas and 108 cases of lower grade gliomas with preoperative MRI, survival data, histology, IDH, and 1p/19q status were included. We proposed a three-level machine-learning model based on multimodal MR radiomics to classify glioma subtypes. An independent dataset with 70 glioma subjects was further collected to verify the model performance.Results: The IDH and 1p/19q status of gliomas can be classified by radiomics and machine-learning approaches, with areas under ROC curves between 0.922 and 0.975 and accuracies between 87.7% and 96.1% estimated on the training dataset. The test on the validation dataset showed a comparable model performance with that on the training dataset, suggesting the efficacy of the trained classifiers. The classification of 5 molecular subtypes solely based on the MR phenotypes achieved an 81.8% accuracy, and a higher accuracy of 89.2% could be achieved if the histology diagnosis is available.Conclusions: The MR radiomics-based method provides a reliable alternative to determine the histology and molecular subtypes of gliomas. Clin Cancer Res; 24(18); 4429–36. ©2018 AACR.

Figure S1. Inclusion Flowchart. Figure S2. Diagram of the image processing. Figure S3. Profiles of the Radiomic Features.

We report a catalytic Friedel–Crafts type arylation of donor–acceptor diazo compounds with aniline derivatives under metal-free and mild conditions.

Aluminum has been extensively used as a conductor material in numerous electronic devices, including solar cells, light-emitting diodes (LEDs), organic LEDs (OLEDs), and thin-film transistors. However, its spiking surface and easy electromigration have limited its performance. To overcome this, a trace amount of nonprecious copper dopant has been proven effective in enhancing device reliability. Nevertheless, a comprehensive investigation regarding the effect of copper doping on the morphology at the aluminum conductor-organic interface is yet to be done. We had hence fabricated a series of green OLED devices to probe how copper doping affected the aluminum conductor, morphologically and electrically, and the corresponding device's efficiency and lifetime performance. We found 4 wt % copper doping to be highly effective in enabling a spike-less and smoother aluminum interface, which in turn enabled the fabrication of devices with much higher efficiency and lifetime. Specifically, the corresponding power efficacy at 1000 cd/m

Background: Studies have shown different gut microbiomes in patients with Parkinson’s disease (PD) compared to unaffected controls. However, when the gut microbiota shift toward dysbiosis in the PD process remains unclear. Objective: We aim to investigate the changes in gut microbiota, locomotor function, and neuropathology longitudinally in PD rodent models. Methods: Fecal microbiota were longitudinally assessed by sequencing the V4–V5 region of the 16S ribosomal RNA gene in a human mutant α-synuclein over-expressing mouse model of PD, SNCA p.A53T mice, and the non-transgenic littermate controls. The locomotor function, neuronal integrity, and α-synuclein expression in the different brain regions were compared between groups. Human fecal microbiota communities from 58 patients with PD and 46 unaffected controls were also analyzed using metagenomic sequencing for comparison. Results: Compared to non-transgenic littermate controls, the altered gut microbiota of the SNCA p.A53T mice can be detected as early as 2 months old, and the diurnal oscillation of the gut microbiome was dampened throughout PD progression starting from 4 months old. However, neuropathology changes and motor deficits were observed starting at 6 months old. Similar changes in altered gut microbiota were also observed in another PD genetic mouse model carrying the LRRK2 p.G2019S mutation at 2 months old. Among the commonly enriched gut microbiota in both PD genetic mouse models, the abundance of Parabateroides Merdae and Ruminococcus torques were also increased in human PD patients compared to controls. Conclusion: These findings revealed the altered gut microbiota communities and oscillations preceding the occurrence of neuropathy and motor dysfunction in the PD process.

Spinal cord often is regarded as one of the last territories in the central nervous system where diffusion tensor imaging (DTI) can be used to probe white matter architecture. This article reviews current progress in spinal cord DTI, starting with anatomic properties and technical challenges that make spinal cord DTI a difficult task. Several possibilities offered by advanced pulse sequences that might overcome the difficulties are addressed, with associated trade-offs and limitations. Potential clinical assistance also is discussed in various spinal cord pathologies, such as myelopathy due to external compression, spinal cord tumors, acute ischemia, traumatic injury, and so forth.

A selective arylation of donor-acceptor diazo compounds with aniline derivatives catalyzed by Lewis acidic boranes is developed. This simple reaction protocol provides an efficient method for the synthesis of diarylacetates under metal-free conditions.

The presence of a swallow-tail sign in the nigrosome-1 with hyperintense signal shown on the susceptibility-weighted imaging (SWI) has been shown to be sensitive in detecting the abnormal iron deposits in this area. A systematic evaluation in healthy subjects is required before this tool can be recommended in a widespread application. We evaluated a simple and practical SWI approach using a multiecho gradient-echo sequence with an improved contrast-to-noise ratio (CNR). We also evaluated the association of the neuromelanin imaging contrast behavior with the susceptibility and relaxation measurements. Twenty-five older and 23 young healthy adults were evaluated. The CNRs of the nigrosome-1 were compared along with method and group. Correlations of the nigrosome-1 neuromelanin signal in the neuromelanin-sensitive imaging with CNRs in the susceptibility, T1 and T2 mappings were examined. Two different coils were used to confirm the reproducibility. Compared with the single-echo, multiecho SWI can improve the CNR of the swallow-tail sign. We found significant correlations between neuromelanin signal and CNRs in the susceptibility and T2 mappings, and T1 value. The older subjects exhibited increased CNRs compared with the young adults. No significant difference was observed in the measurements between 20 and 64 channels. The multiecho technique allows the high-quality nigrosome-1 images in SWI and allows for a joint analysis of T2* and quantitative-susceptibility mapping at high spatial resolution. The correlations of neuromelanin-sensitive imaging with susceptibility and T2 imply that the iron content in the nigrosome-1 may have significant influences on the hyperintensity of neuromelanin in the magnetization transfer-related contrast.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with chemo-resistant, immunosuppressive, and invasive property. Despite the application of standard therapies which include a combination of surgery, radiotherapy, and temozolomide (TMZ) chemotherapy, tumor inevitably recurred (in patients) at peritumoral region. Targeting multiple arms of the GBM-mediated immunosuppressive ability and their invasiveness can improve therapeutic efficacy. Genomic screening identified that IL-19 is a predicted immune suppressive cytokine in peritumoral region and was associated with poor survival in patients with GBM. IL-19 blockade inhibited both TMZ-sensitive and resistant tumor progression. Molecular studies revealed that silencing IL-19 markedly abrogated IL-19-WISP1-AKT signaling to inhibit TMZ-resistant GBM cell invasion, as well as weaken its suppressive ability on CD8+T cell activation. Single cell transcriptome analysis revealed that IL-19 blockade promoted T cell activation, upregulated effector function of T cell subsets, and reprogrammed tumor-associated macrophage subsets toward a weakened pro-tumoral phenotypes. Thus, Targeting IL-19 can be a novel therapeutic strategy to reverse immunosuppressive microenvironment and restrict invasiveness of chemo-resistant GBM. Citation Format: Gilbert A. Lee, Cheng-Yu Chen. IL-19 blockade reprograms glioblastoma immunosuppressive microenvironment and overcomes chemo-resistance as revealed by single-cell transcriptome analyses. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5652.

Rheumatic heart disease (RHD) remains a critical problem in developed countries. Few studies have compared the long-term outcomes of bioprosthetic valves and mechanical valves in patients with RHD who have received mitral valve (MV) replacement.Patients with RHD who received MV replacement with bioprosthetic or mechanical valves were identified between 2000 and 2013 from Taiwan's National Health Insurance Research Database. The primary late outcomes of interest were all-cause mortality and redo MV surgery. Propensity score matching at a 1:1 ratio was performed.We identified 3638 patients with RHD who underwent MV replacement. Among those patients, 1075 (29.5%) and 2563 (70.5%) chose a bioprosthetic valve and mechanical valve, respectively. After matching, 788 patients were assigned to each group. No significant difference in the risk of in-hospital mortality was observed between groups (P = .920). Higher risks of all-cause mortality (10-year actuarial estimates: 50.6% vs 45.5%; hazard ratio, 1.19; 95% confidence interval, 1.01-1.41; P = .040) and MV reoperation (10-year actuarial estimates: 8.9% vs 0.93%; subdistribution hazard ratio, 4.56; 95% confidence interval, 1.71-12.17; P .01) were observed in the bioprosthetic valve group. Furthermore, the relative mortality benefit associated with mechanical valves was more apparent in younger patients and the beneficial effect persisted until approximately 65 years of age.In the patients with RHD who underwent MV replacement, mechanical valves were associated with more favorable long-term outcomes in patients younger than the age of 65 years.

Fifth-generation mobile communication networks (5G)/Beyond 5G (B5G) can achieve higher data rates, more significant connectivity, and lower latency to provide various mobile computing service categories, of which enhanced mobile broadband (eMBB), massive machine-type communications (mMTC), and ultra-reliable and low latency communications (URLLC) are the three extreme cases. A symmetrically balanced mechanism must be considered in advance to fit the different requirements of such a wide variety of service categories and ensure that the limited resource capacity has been properly allocated. Therefore, a new network service architecture with higher flexibility, dispatchability, and symmetrical adaptivity is demanded. The cloud native architecture that enables service providers to build and run scalable applications/services is highly favored in such a setting, while a symmetrical resource allocation is still preserved. The microservice function in the cloud native architecture can further accelerate the development of various services in a 5G/B5G mobile wireless network. In addition, each microservice part can handle a dedicated service, making overall network management easier. There have been many research and development efforts in the recent literature on topics pertinent to cloud native, such as containerized provisioning, network slicing, and automation. However, there are still some problems and challenges ahead to be addressed. Among them, optimizing resource management for the best performance is fundamentally crucial given the challenge that the resource distribution in the cloud native architecture may need more symmetry. Thus, this paper will survey cloud native mobile computing, focusing on resource management issues of network slicing and containerization.

This article presents the 38-GHz phased array 32-element Tx and 16-element Rx with 2-GHz IF and 5-GHz LO for fifth-generation (5G) millimeter-wave (MMW) communications. The Tx and Rx beamformers and upconverters/downconverters are fabricated in 65-nm CMOS. The PAs and LNAs near antenna ends are fabricated in 0.15- $\mu \text{m}$ GaAs pHEMT. The eight-element Tx and four-element Rx phased array printed circuit board (PCB) modules integrated with multiple integrated circuits (ICs) and endfire antennas are implemented as unit cells. Four pieces of Tx modules are vertically stacked to construct an $8\times {4}$ brick array (planar array), while four Rx modules are to construct a $4\times {4}$ array. According to 38-GHz over-the-air (OTA) measurements, the 32-element Tx shows 47.5-dBm equivalent isotropic radiated power (EIRP) at OP $_{\mathrm {1 ~dB}}$ with −35.2-dB image rejection ratio (IMRR) and −37.4-dB $\times 8$ LORR. The 16-element Rx at 38 GHz shows −4-dBm OP $_{\mathrm {1~dB}}$ with −28-dB IMRR and −36.6-dB LORR. The Tx and Rx support the beam scanning around ±60° azimuth and ±30° elevation planes. The Tx-to-Rx wireless data link demonstrates 64 quadrature amplitude modulation (QAM)/400 M-BR, 256 QAM/200 M-BR, and 512 QAM/100 M-BR in 20 m. To the best of our knowledge, this work is the first 5G 37-/39-GHz phased array Tx/Rx using the scalable brick array configuration and demonstrating competitive performances compared with previous works.

Background/Purpose Sjogren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of TH1 and TH2 cytokines and increasing salivary flow rate. A newly designed traditional Chinese medicine, SS-1, showed improved efficacy in alleviating the dryness symptoms of SS patients in the National Taiwan SS cohort investigation. Here, we investigated the effect of SS-1 on T cell responses. Methods SS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and TH1, TH2, and TH17 polarization of murine T cells. We also determined the level of TH1, TH2, and TH17 cytokine RNA in peripheral blood mononuclear cells of SS patients before and after SS-1 treatment. Results SS-1 treatment inhibits the activation and TH1, TH2, and IL-17A+IFNγ+ TH polarization of murine T cells. SS-1 treatment also significantly reduces IFN-γ, IL-4, and IL-13 expression, and moderately reduces IL-17A expression in peripheral blood mononuclear cells of SS patients. Conclusion Our results suggest that SS-1 inhibits T cell activation and diminishes TH1, TH2, and IL-17+IFN-γ+ TH responses in SS patients.

Lignocelluloses are comprised of cellulose, hemicellulose, and lignins, which constitute plant biomass. Since peroxidases can degrade lignins, the authors examined peroxidase Tfu-1649, which is secreted from the thermophilic actinomycetes, Thermobifida fusca BCRC 19214. After cultivating for 48 h, the culture broth accumulated 43.66 U/mL of peroxidase activity. The treatment of four types of lignocellulolytic byproducts, i.e., bagasse, corncob, pin sawdust, and Zizania latifolia Turcz husk, with Tfu-1649 alone increased the total phenolic compounds, with limited reducing sugars, but treatment with xylanase, Tfu-11, and peroxidase Tfu-1649 showed synergistic effects. Hence, the co-operative degradation of lignocelluloses by both peroxidase and xylanase could contribute to biomass decomposition and further applications in the agricultural and environmental industries.

Heme‐nitric oxide/oxygen binding (H‐NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacterium Shewanella woodyi (Sw), H‐NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H‐NOX domain to induce cyclase activity and regulate vascular tone, wound healing and memory formation. sGC also binds stimulator compounds targeting cardiovascular disease. The molecular details of stimulator binding to sGC remain obscure but involve a binding pocket near an interface between H‐NOX and coiled‐coil domains. Here, we report the full NMR structure for CO‐ligated Sw H‐NOX in the presence and absence of stimulator compound IWP‐051, and its backbone dynamics. Nonplanar heme geometry was retained using a semi‐empirical quantum potential energy approach. Although IWP‐051 binding is weak, a single binding conformation was found at the interface of the two H‐NOX subdomains, near but not overlapping with sites identified in sGC. Binding leads to rotation of the subdomains and closure of the binding pocket. Backbone dynamics are similar across both domains except for two helix‐connecting loops, which display increased dynamics that are further enhanced by compound binding. Structure‐based sequence analyses indicate high sequence diversity in the binding pocket, but the pocket itself appears conserved among H‐NOX proteins. The largest dynamical loop lies at the interface between Sw H‐NOX and its binding partner as well as in the interface with the coiled coil in sGC, suggesting a critical role for the loop in signal transduction.

A new podocarpane type diterpenoid, aculeatusane A (1), and six known diterpenoids (2-7) were isolated from the whole plants of Celastrus aculeatus Merr. (Celastraceae). The structures were identified based on the HRESIMS and NMR spectroscopic data. All diterpenoids were isolated from C. aculeatus for the first time. Antiviral activity assay showed that aculeatusane A (1) is active against A/GZ/GIRD07/09 (H1N1) with the selectivity index (SI) of 6.75 ± 4.38.

In this paper, we propose a scheme named “Adaptive Clustering and Scheduling for Dynamic Region-based Resource Allocation” (ACSR) to solve the problems in 3GPP’s fixed zone resource allocation schemes for 3GPP’s infrastructure-aided Vehicle-to-Vehicle (V2V) communication technology:Cellular V2V or C-V2V communications. In 3GPP’s fixed-zone resource allocation schemes, the radio channels are separated into groups each of which is reused amid pre-determined geographical zones with a fixed area and locations regardless of the number of vehicles sharing the group of channels assigned to a zone. On the other hand, in the proposed ACSR scheme, vehicles are dynamically and adaptively clustered by their geographical locations and banks of radio channels are reused amid clusters. This flexibility of vehicle clustering in which the number of vehicles in a cluster could fit the number of channels in a re-usable group of channels largely reduces the chance of co-channel interference and hence improve the transmission performance. A vehicle in a cluster is elected to be the cluster head for assigning radio channels to those which in its cluster are about to transmit so that both the overhead of signaling transmissions and computation complexity at eNB/gNB are reduced. The performance of ACSR are compared with several other typical resource allocation schemes by extensive simulations under the simulation scenario setting defined by 3GPP specifications. The performance metrics are (1) the average computation offloading ratio (COR) in reference to the centralized brute-force optimization scheme at eNB/gNB and (2) the average successful packet reception ratio (PRR) defined in 3GPP specification. The average COR for ACSR is 30.9%. The ACSR’s average PRR improvements over a typical fixed zone resource allocation scheme, the FZRA scheme, are greater than 5%, 10% and 21.8% when the transmission distance is 120 meters, 180 meters, and 320 meters, respectively. Simulation results shown that in general the ACSR scheme significantly improves the performance as compared to 3GPP’s fixed zone resource allocation schemes.

The Asclepiadaceae plant is a rich source of C21 steroidal glycosides. The present study aimed to investigate the C21 steroidal glycosides from the whole plants of Tylophora atrofolliculata (Asclepiadaceae). As a result, three new C21 steroidal glycosides named atrofollicosides A-C (1-3) and four known steroidal glycosides (4-7) were isolated. The structures of these compounds were characterized using NMR spectroscopy. Highlighted here is a new disecopregnane-type steroid with a hydroxyl group at the C-18 position that constitutes the aglycone of compound 1.

Overexpression and/or overactivation of the Epidermal Growth Factor Receptor (EGFR) is oncogenic in several tumor types yet targeting the kinase domain of wildtype EGFR has had limited success. EGFR has numerous kinase-independent roles, one of which is accomplished through the Sorting Nexin-dependent retrotranslocation of EGFR to the nucleus, which is observed in some metastatic cancers and therapeutically resistant disease. Here, we have utilized the BAR domain of Sorting Nexin 1 to create a peptide-based therapeutic (cSNX1.3) that promotes cell death in EGFR-expressing cancer. We evaluated the efficacy of cSNX1.3 in tumor-bearing WAP-TGFα transgenic mice (an EGFR-dependent model of breast cancer), where cSNX1.3 treatment resulted in significant tumor regression without observable toxicity. Evaluation of remaining tumor tissues found evidence of increased PARP cleavage, suggesting apoptotic tumor cell death. To evaluate the mechanism of action for cSNX1.3, we found that cSNX1.3 binds the C-terminus of the EGFR kinase domain at an interface site opposite the ATP binding domain with a Kd of ~4.0 µM. In vitro analysis found that cSNX1.3 inhibits the nuclear localization of EGFR. To determine specificity, we evaluated cancer cell lines expressing wildtype EGFR (MDA-MB-468, BT20 and A549), mutant EGFR (H1975) and non-transformed lines (CHO and MCF10A). Only transformed lines expressing wildtype EGFR responded to cSNX1.3, while mutant EGFR and normal cells responded better to an EGFR kinase inhibitor. Phenotypically, cSNX1.3 inhibits EGF-, NRG-, and HGF-dependent migration, but not HA-dependent migration. Together, these data indicate that targeting retrotranslocation of EGFR may be a potent therapeutic for RTK-active cancer.

Background and PurposeBenzimidazoles have attracted much attention over the last few decades due to their broad-spectrum pharmacological properties. Increasing evidence is showing the potential use of benzimidazoles as anti-angiogenic agents, although the mechanisms that impact angiogenesis remain to be fully defined. In this study, we aim to investigate the anti-angiogenic mechanisms of MFB, a novel 2-aminobenzimidazole derivative, to develop a novel angiogenesis inhibitor.Experimental ApproachMTT, BrdU, migration and invasion assays, and immunoblotting were employed to examine MFB’s effects on vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration, invasion, as well as signaling molecules activation. The anti-angiogenic effects of MFB were analyzed by tube formation, aorta ring sprouting, and matrigel plug assays. We also used a mouse model of lung metastasis to determine the MFB’s anti-metastatic effects.Key ResultsMFB suppressed cell proliferation, migration, invasion, and endothelial tube formation of VEGF-A-stimulated human umbilical vascular endothelial cells (HUVECs) or VEGF-C-stimulated lymphatic endothelial cells (LECs). MFB suppressed VEGF-A and VEGF-C signaling in HUVECs or LECs. In addition, MFB reduced VEGF-A- or tumor cells-induced neovascularization in vivo. MFB also diminished B16F10 melanoma lung metastasis. The molecular docking results further showed that MFB may bind to VEGFR-2 rather than VEGF-A with high affinity.Conclusions and ImplicationsThese observations indicated that MFB may target VEGF/VEGFR signaling to suppress angiogenesis and lymphangiogenesis. It also supports the role of MFB as a potential lead in developing novel agents for the treatment of angiogenesis- or lymphangiogenesis-associated diseases and cancer.

Additional file 2.

Additional file 1.

Background: To investigate whether serial morphometric measurements of the brainstem using high resolution trans-foramen-magnum ultrasound (US) in premature neonates correlate with neurological outcomes.Methods: Serial brain ultrasound scans were performed in 36 consecutive preterm infants born at Results: Of the 36 preterm infants born between 25 and 34 weeks of gestation, eight had significantly delayed growth profiles in both the pons and medulla and developed neurological sequelae by 5 years of age.Conclusions: Morphometric measurements of the developing brainstem using high resolution trans-foramen-magnum ultrasound (US) may help predict neurological outcome in high-risk neonates, particularly in those who are born extremely premature.

Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear, because abnormality is often absent in structural imaging findings. Previous studies have demonstrated that WM functional activity estimated from functional magnetic resonance imaging (fMRI) has a high sensitivity to postconcussion WM deficits and may be used to not only evaluate but guide treatment strategies, especially targeting brain areas involved in postconcussion cognitive decline. The purpose of the study was to determine whether machine learning-based models using fMRI biomarkers and demographic or neuropsychological measures at the baseline could effectively predict the 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically matched healthy controls enrolled between September 2015 and August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to their significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after a concussion. Approximately half of the patients experienced prolonged cognitive impairment at the 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy = 87.5%), 6 months (accuracy = 83.3%), and 1 year (accuracy = 83.3%) and performed worse at the 1-year follow-up compared to the baseline assessment (accuracy = 83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.

A well-established lung-cancer-survival-prediction model that relies on multiple data types, multiple novel machine-learning algorithms, and external testing is absent in the literature. This study aims to address this gap and determine the critical factors of lung cancer survival. We selected non-small-cell lung cancer patients from a retrospective dataset of the Taipei Medical University Clinical Research Database and Taiwan Cancer Registry between January 2008 and December 2018. All patients were monitored from the index date of cancer diagnosis until the event of death. Variables, including demographics, comorbidities, medications, laboratories, and patient gene tests, were used. Nine machine-learning algorithms with various modes were used. The performance of the algorithms was measured by the area under the receiver operating characteristic curve (AUC). In total, 3714 patients were included. The best performance of the artificial neural network (ANN) model was achieved when integrating all variables with the AUC, accuracy, precision, recall, and F1-score of 0.89, 0.82, 0.91, 0.75, and 0.65, respectively. The most important features were cancer stage, cancer size, age of diagnosis, smoking, drinking status, EGFR gene, and body mass index. Overall, the ANN model improved predictive performance when integrating different data types.

Background: Cholinergic deficiency has been suggested to associate with the abnormal accumulation of Aβ and tau for patients with Alzheimer's disease (AD). However, no studies have investigated the effect of APOE-ε4 and group differences in modulating the cholinergic basal forebrain–amygdala network for subjects with different levels of cognitive impairment. We evaluated the effect of APOE-ε4 on the cholinergic structural association and the neurocognitive performance for subjects with different levels of cognitive impairment.Methods: We used the structural brain magnetic resonance imaging scans from the Alzheimer's Disease Neuroimaging Initiative dataset. The study included cognitively normal (CN, n = 167) subjects and subjects with significant memory concern (SMC, n = 96), early mild cognitive impairment (EMCI, n = 146), late cognitive impairment (LMCI, n = 138), and AD (n = 121). Subjects were further categorized according to the APOE-ε4 allele carrier status. The main effects of APOE-ε4 and group difference on the brain volumetric measurements were assessed. Regression analyses were conducted to evaluate the associations among cholinergic structural changes, APOE-ε4 status, and cognitive performance.Results: We found that APOE-ε4 carriers in the disease group showed higher brain atrophy than non-carriers in the cholinergic pathway, while there is no difference between carriers and non-carriers in the CN group. APOE-ε4 allele carriers in the disease groups also exhibited a stronger cholinergic structural correlation than non-carriers did, while there is no difference between the carriers and non-carriers in the CN subjects. Disease subjects exhibited a stronger structural correlation in the cholinergic pathway than CN subjects did. Moreover, APOE-ε4 allele carriers in the disease group exhibited a stronger correlation between the volumetric changes and cognitive performance than non-carriers did, while there is no difference between carriers and non-carriers in CN subjects. Disease subjects exhibited a stronger correlation between the volumetric changes and cognitive performance than CN subjects did.Conclusion: Our results confirmed the effect of APOE-ε4 on and group differences in the associations with the cholinergic structural changes that may reflect impaired brain function underlying neurocognitive degeneration in AD.

Communication services have become increasingly widespread in recent years. The fifth generation mobile communication standard organizations have set and adopted relevant standards, especially the Third Generation Partnership Project (3GPP). In addition to improving the efficiency of spectrum use and saving energy, how to serve narrow-band networking such as narrow-band internet of thing (NB-IoT) is also very important in the fifth-generation mobile communications. Spectral network layer with network slicing resource allocation (RA) is used in this paper so that the user equipment (UE) can meet the minimum quality of service (QoS) under the OFDMA (Orthogonal Frequency Division Multiple Access) environment. The problem is characterized as an optimization problem, and a Heuristic algorithm is designed to solve it.

In this digital era, young children spend a considerable amount of time looking at telephone, tablet, computer and television screens. However, preventative eye health behavior education could help avoid and relieve asthenopia. The effects of parental influence on their children’s eye health behavior through the preschool eye health education intervention program were examined. The Health Belief Model was used to develop parental involvement strategy and eye health curriculum. The study was conducted in a large public preschool with five branches in Beijing, China. A total of 248 parent–child pairs participated in the baseline and follow-up surveys, of which 129 were in the intervention group and 119 were in the comparison group. The generalized estimating equation analysis results indicated that parental involvement in preschool-based eye health intervention on screen uses had positive influence on parents’ eye health knowledge, cues to action, and parenting efficacy. The intervention program also had positive effects on the increasing level of children’s eye health knowledge, beliefs, cues to action, self-efficacy, and behaviors. The results supported the implementation of a preschool-based eye health intervention program with parental involvement, which could potentially enhance children’s and parents’ eye health beliefs and practices.

Objective: Many women quit smoking during pregnancy resume in postpartum period and difficult to prevent. No studies had focused on their psychosocial response in Taiwan. We analyzed data from a trial of Taiwan Smoker's Helpline (TSH) to determine factors associated with smoking relapse after delivery. Materials and methods: A prospective cohort was conducted at Taipei City Hospital during Sep. 2014 and Nov. 2015 period. We collected data by self-developed questionnaire combining theory of planned behavior (TPB), Fagerstrom test for nicotine dependence (FTND) and Edinburgh Postnatal Depression Scale (EPDS) from 68 women immediately after delivery, 2 months later and followed up until 6 months. Multivariable logistic models for relapse of smoking at the end of 3rd month and 6th month were created. Results: At 6th month, 42.6% participants relapsed with odds lower among first parity (OR = 0.04, 95% CI =

Background The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings. Aims This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study. Methods A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan’s National Health Insurance Research Database. The Kaplan–Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC. Results The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P Conclusions Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.

A phenanthroindolizidine glycoside 6-O-β-D-glucopyranosyl-tylophorinidine (1), the first glycoside of phenanthroindolizidine alkaloid in nature, was isolated from whole plants of Tylophora atrofolliculata (Asclepiadaceae). Its structure was elucidated by means of spectral and chemical evidences. Compound 1 showed potent inhibitory effect (IC50: 69 ± 13 nM) on hypoxia induced factor-1 (HIF-1) activation. It was discovered that glucosylation at C-6 of 1 could lead to reduction in cytotoxicity against normal cells and enhance its selectivity in tumor cells inhibition.

Introduction: Recent trials have demonstrated the superior efficacy of mechanical thrombectomy over other medical treatments for acute ischemic stroke; however, not every large vessel occlusion (LVO) can be recanalized using a single thrombectomy device. Rescue devices were proved to increase the reperfusion rate, but the efficacy is unclear.Objective: In this retrospective study, we evaluated the efficacy of rescue therapy in different locations of LVO.Methods: We analyzed the outcomes of mechanical thrombectomy from a prospective registry of consecutive 82 patients in Taipei Medical University Hospital. The reperfusion rate and the functional outcome were compared in patients who received first-line therapy only and patients who need rescue therapy.Results: An 84.1% reperfusion rate was achieved in our cohort. We applied first-line stent retriever (SR) treatment in 6 patients, among which 4 (66.6%) achieved successful reperfusion. We applied a direct-aspiration first-pass technique (ADAPT) as the first-line treatment in 76 patients, among which 46 (60.5%) achieved successful reperfusion. Successful reperfusion could not be achieved in 30 cases (39.5%); therefore, we applied a second-line rescue SR for 28 patients, and reperfusion was established in 18 (64.3%) of them. These results revealed that the LVO in anterior circulation has a higher chance to respond to SR rescue therapy than posterior circulation lesions (68 vs. 33.3%, P < 0.001). Patients who received only first-line therapy exhibited significantly better functional outcomes than those who were also treated with rescue SR therapy (41.2 vs. 16.7%, P = 0.001). In addition, patients with LVO in the anterior circulation were found to have a higher probability of achieving functional independence than patients with posterior circulation lesions (10.7 vs. 0.0%, P < 0.001). The adjusted multivariate analysis revealed that successful reperfusion and treatment type (first-line or rescue therapy) were significantly related to a modified Rankin Scale (mRS) score at 90 days.Conclusion: This study reveals that rescue SR therapy improves the reperfusion rate. Patients who require rescue SR therapy have a lower likelihood of functional independence. LVO in the anterior circulation responds better to rescue SR therapy and results in better functional outcomes than posterior circulation lesions.

Background: Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide-resistant. Diagnostic probes targeting PD-L1 could help early diagnosis and be used to predict the responses of targeted PD-L1 immunotherapy in patients with primary and recurrent glioblastoma. In this study, we conjugated lipid-coated SPIO nanoparticles with PDL1 antibodies to identify PDL1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI.Results: The synthesized PD-L1 antibody–conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, in vitro cell affinity assay, and in vivo MRI analysis. These data demonstrated that PDL1-SPIO has a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2* map MRI, respectively.Conclusions: These findings revealed that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression and can be quantified with MRI analysis, thereby making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.

Purpose Medulloblastoma (MB) is a highly malignant pediatric brain tumor. In the latest classification, medulloblastoma is divided into four distinct groups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We analyzed the magnetic resonance imaging radiomics features to find the imaging surrogates of the 4 molecular subgroups of MB. Material and methods Frozen tissue, imaging data, and clinical data of 38 patients with medulloblastoma were included from Taipei Medical University Hospital and Taipei Veterans General Hospital. Molecular clustering was performed based on the gene expression level of 22 subgroup-specific signature genes. A total 253 magnetic resonance imaging radiomic features were generated from each subject for comparison between different molecular subgroups. Results Our cohort consisted of 7 (18.4%) patients with WNT medulloblastoma, 12 (31.6%) with SHH tumor, 8 (21.1%) with Group 3 tumor, and 11 (28.9%) with Group 4 tumor. 8 radiomics gray-level co-occurrence matrix texture (GLCM) features were significantly different between 4 molecular subgroups of MB. In addition, for tumors with higher values in a gray-level run length matrix feature—Short Run Low Gray-Level Emphasis, patients have shorter survival times than patients with low values of this feature (p = 0.04). The receiver operating characteristic analysis revealed optimal performance of the preliminary prediction model based on GLCM features for predicting WNT, Group 3, and Group 4 MB (area under the curve = 0.82, 0.72, and 0.78, respectively). Conclusion The preliminary result revealed that 8 contrast-enhanced T1-weighted imaging texture features were significantly different between 4 molecular subgroups of MB. Together with the prediction models, the radiomics features may provide suggestions for stratifying patients with MB into different risk groups.

Background/purpose Several growth factors were proven to be effective in the treatment of bone defects and fractures and thus have great potential for bone regeneration applications. However, it needs low-temperature storage and transportation. This study aimed to investigate the herbal extract quercetin, a candidate for natural flavonoid compounds that have been reported to be involved in regulating inflammation and improving immunity and health. Methods In this study, we prepared quercetin (Q)/mesoporous calcium silicate calcium sulfate (MSCS)/polycaprolactone (PCL) composite scaffolds using the 3D printing technique, where we immersed it in simulated body fluid (SBF) solution and soaked it for up to 60 days. The characteristics of quercetin scaffold were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), immunofluorescence, and Alizarin Red S staining. Results We found precipitation of apatite on the surface of the scaffold. The in vitro results for cell proliferation, cytotoxicity, and immunofluorescence staining revealed that Wharton's jelly mesenchymal stem cells (WJMSCs) with a 2% quercetin (Q2) scaffold were significantly higher in number than with 1% quercetin (Q1) and MSCS scaffolds. The phalloidin staining of cell skeletons on the surface of Q2 revealed powerful cell-to-cell adhesion and high expression of green fluorescence. The Q2 scaffold also had the highest calcium deposit levels based on Alizarin Red S staining in all scaffolds. This indicated that quercetin was able to induce cell growth and mitosis, echoing the previous preliminary results. Conclusion Our initial results indicate that this natural herbal extract can be a good bone-based gene substitution for bone regeneration.

Heme-nitric oxide/oxygen binding (H-NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacterium Shewanella woodyi (Sw), H-NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H-NOX domain to induce cyclase activity and regulate vascular tone, wound healing and memory formation. sGC also binds stimulator compounds targeting cardiovascular disease. The molecular details of stimulator binding to sGC remain obscure but involve a binding pocket near an interface between H-NOX and coiled-coil domains. Here, we report the full NMR structure for CO-ligated Sw H-NOX in the presence and absence of stimulator compound IWP-051, and its backbone dynamics. Non-planar heme geometry was retained using a semi-empirical quantum potential energy approach. Although IWP-051 binding is weak, a single binding conformation was found at the interface of the two H-NOX subdomains. Binding lead to rotation of the subdomains and closure of the binding pocket. Backbone dynamics for the protein are similar across both domains except for two helix-connecting loops, which display increased dynamics that are further enhanced by compound binding. Structure-based sequence analyses indicate high sequence diversity in the binding pocket, but the pocket itself appears conserved among H-NOX proteins. The largest dynamical loop lies at the interface between Sw H-NOX and its binding partner as well as in the interface with the coiled coil in sGC, suggesting a critical role for the loop in signal transduction.

Deep learning for digital pathology is hindered by the extremely high spatial resolution of whole slide images (WSIs). Most studies adopt patch-based methods which, however, require well annotated data for training. These are typically done by laboriously free-hand contouring on the WSI by experts. To both alleviate annotation burdens of experts and enjoy benefits from scaling up amounts of data, we develop a whole-slide training method for entire WSIs to classify types of lung cancers using slide-level diagnoses. Our method leverages unified memory to offload the excessive amount of memory consumption to host memory to train a classifier by entire hundreds-of-million-pixels slides. Experiments were conducted on the lung cancer dataset which contains 9,662 digital slides with various main types. The results showed that the proposed method can achieve an AUC of 0.950 and 0.924 for adenocarcinoma and squamous cell carcinoma on a separate testing set respectively. Furthermore, critical regions highlighted by the class activation map (CAM) technique of our model reveals a high correspondence to cancerous areas annotated by pathologists.