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Purpose:Induction cisplatin and gemcitabine chemotherapy is a standard treatment for locally advanced nasopharyngeal carcinoma (NPC). Inhibition of VEGF axis has been shown to promote maturation of microvasculature and improve perfusion. We conducted a four-arm study to assess the effect of two doses of either sunitinib or bevacizumab with chemotherapy in NPC.Patients and Methods:Patients with treatment-naïve locally advanced NPC were treated with three cycles of 3-weekly cisplatin and gemcitabine preceded by 1 week of anti-VEGF therapy for each cycle, followed by standard concurrent chemoradiation: arm A patients received 7 days of 12.5 mg/day sunitinib; arm B 7 days of 25 mg/day sunitinib; arm C bevacizumab 7.5 mg/kg infusion; arm D bevacizumab 2.5 mg/kg infusion. Patients with metastatic NPC were treated with up to six cycles of similar treatment without concurrent chemoradiation.Results:Complete metabolic response (mCR) by whole body 18FDG PET was highest in arm C (significant difference in four groups Fisher exact test P = 0.001; type 1 error = 0.05), with 42% mCR (95% confidence interval, 18–67) and 3-year relapse-free survival of 88% in patients with locally advanced NPC. Significant increase in pericyte coverage signifying microvascular maturation and increased immune cell infiltration was observed in posttreatment tumor biopsies in Arm C. Myelosuppression was more profound in sunitinib containing arms, and tolerability was established in arm C where hypertension was the most significant toxicity.Conclusions:Bevacizumab 7.5 mg/kg with cisplatin and gemcitabine was well tolerated. Promising tumor response was observed and supported mechanistically by positive effects on tumor perfusion and immune cell trafficking into the tumor.

Figure S1- Study schema Figure S2 - Example of complete metabolic response after 3 cycles of induction therapy in a representative Arm C patient treated with bevacizumab at 7.5mg/kg in combination with cisplatin and gemcitabine. Figure S3- Relapse free survival (RFS) in months by study arms of patients with locally advanced disease who underwent concurrent chemoradiation after induction chemotherapy. Figure S4 - Relapse free survival in months by metabolic response to induction therapy. Figure S5 - (A) Spaghetti Plot of EBV viral load at baseline (BL), C2D1 and C3D1; (B)Circulating VEGF levels in plasma samples collected at BL, C1D1, C2D1 and end of induction therapy, EOT. Figure 6a- Figure S6 - Induction of mature blood vessel in the NPC tumour microenvironment 7 days following initiation of sunitinib and bevacizumab exposure. Figure S6b - Quantification of blood vessel densities Figure S7- Immune cell infiltration in the NPC tumour microenvironment 7 days following initiation of sunitinib or bevacizumab exposure

Supplementary methods and supplementary tables

This letter presents a shoe-integrated fall detection system that is based on seven time-of-flight (ToF) range sensors to identify falls on different terrains. The ToF range sensors, which measure the real-time distance between the sensors and the ground surface, can be used to detect simultaneously the variation of the gait cycle and the geometry of the terrain. Using the statistical features of the ToF range signals and an error-correcting output codes-based model, 17 experimental activities, executed by nine participants, are classified into three classes—activities of daily life, near falls, and falls. The experimental F1-scores for these three classes are 100, 98.17, and 99.07%, respectively. The arrangement of ToF range sensors is simplified to develop a compact shoe-integrated system architecture for fall detection.

IntroductionMany regions in the world are using the population health approach and require a means to measure the health of their population of interest. Population health frameworks provide a theoretical grounding for conceptualization of population health and therefore a logical basis for selection of indicators. The aim of this scoping review was to provide an overview and summary of the characteristics of existing population health frameworks that have been used to conceptualize the measurement of population health.MethodsWe used the Population, Concept and Context (PCC) framework to define eligibility criteria of frameworks. We were interested in frameworks applicable for general populations, that contained components of measurement of health with or without its antecedents and applied at the population level or used a population health approach. Eligible reports of eligible frameworks should include at least domains and subdomains, purpose, or indicators. We searched 5 databases (Pubmed, EMBASE, Web of Science, NYAM Grey Literature Report, and OpenGrey), governmental and organizational sites on Google and websites of selected organizations using keywords from the PCC framework. Characteristics of the frameworks were summarized descriptively and narratively.ResultsForty-eight frameworks were included. The majority originated from the US (42%), Canada (23%) and Europe (23%). Apart from 1 framework developed for rural populations and 2 for indigenous populations, the rest were for general urban populations. The numbers of domains, subdomains and indicators were highly variable. Health status and social determinants of health were the most common domains across all frameworks. Different frameworks had different priorities and therefore focus on different domains.ConclusionKey domains common across frameworks other than health status were social determinants of health, health behaviours and healthcare system performance. The results in this review serve as a useful resource for governments and healthcare organizations for informing their population health measurement efforts.

Summary The family is an important contributor to the cultural conditions that support health. Current challenges in family health promotion interventions include programme design that is not always guided by theory and change mechanisms. Multifaceted programmes also make it hard to examine what works for whom, given different family roles and the range of lifestyle behaviour and mechanisms examined within diverse conceptual frameworks and cultures. We performed a scoping review on the heterogeneous literature to map and categorize the models and mechanisms by which a family may promote health behaviours among its members. We searched five electronic databases and grey literature up to 2020. Publications were included if they examined health-promoting behaviours, influences at the family level, and outlined the behavioural mechanisms involved. Two hundred and forty studies were identified. Ecological systems theory, social cognitive theory, family systems theory and the theory of planned behaviour were the frameworks most widely used in explaining either study context and/or mechanism. The most frequently studied family mechanisms involved aspects of family support, supervision and modelling, while some studies also included individual-level mechanisms. Majority of the studies investigated parental influence on the child, while few studies assessed the elderly family member as a recipient or actor of the influences. Studies on African, Asian and Middle Eastern populations were also in the minority, highlighting room for further research. Improving the understanding of context and behavioural mechanisms for family health promotion will aid the development of public health policy and chronic disease prevention programmes, complementing efforts targeted at individuals.

Glioblastoma multiforme (GBM) is the most aggressive and mortal primary glioma in adults. Temozolomide (TMZ) is a first-line clinical chemotherapeutic drug. However, TMZ resistance causes treatment failure in patients. Thus, exploring effective adjuvant drugs for GBM is crucial. Piperlongumine (PL), a bioactive alkaloid isolated from long pepper, possesses promising anticancer abilities. However, PL-mediated cytotoxic mechanisms in GBM are still unclear. We attempted to identify PL-regulated networks in suppressing GBM malignancy.PL treatment significantly induced more apoptotic death in several GBM cell lines than in normal astrocytes. Decreased cell invasion, colony generation, and sphere formation, and enhanced TMZ cytotoxicity were found in PL-treated cells. Through RNA sequencing, PL-mediated transcriptomic profiles were established. By intersecting PL-downregulated genes, higher expressing genes in The Cancer Genome Atlas (TCGA) tumor tissues, and risk genes in three different GBM databases, tripartite motif-containing 14 (TRIM14) was selected. Higher TRIM14 expression was correlated with poor patient survival, and it existed in tumor samples, in mesenchymal type of GBM patients, and in GBM cells. PL significantly reduced TRIM14 expression through activating the p38/MAPK pathway. Overexpression or knockdown of TRIM14 influenced cell growth, PL-inhibited cell viability, invasion, colony generation, and sphere formation. Finally, using a gene set enrichment analysis, genes positively correlated with TRIM14 levels were enriched in epithelial-to-mesenchymal transition signaling. TRIM14 overexpression attenuated PL-regulated mesenchymal transition signaling.PL inhibited TRIM14 signaling through activating the p38/MAPK pathway to inhibit GBM malignancy. Our findings may provide better insights and directions for future GBM therapies.

We report the development of novel cannabinergic probes that can stabilize the cannabinoid receptors (CBRs) through tight binding interactions. Ligand design involves the introduction of select groups at a judiciously chosen position within the classical hexahydrocannabinol template (monofunctionalized probes). Such groups include the electrophilic isothiocyanato, the photoactivatable azido, and the polar cyano moieties. These groups can also be combined to produce bifunctionalized probes potentially capable of interacting at two distinct sites within the CBR-binding domains. These novel compounds display remarkably high binding affinities for CBRs and are exceptionally potent agonists. A key ligand (27a, AM11245) exhibits exceptionally high potency in both in vitro and in vivo assays and was designated as "megagonist," a property attributed to its tight binding profile. By acting both centrally and peripherally, 27a distinguishes itself from our previously reported "megagonist" AM841, whose functions are restricted to the periphery.

The stereocomplexation of poly(methyl methacrylate) (PMMA) is a unique supramolecular assembling system that has been demonstrated to be valuable in many applications. The crystallization behaviors of stereocomplex PMMA (sc-PMMA) under nanoconfinement, however, have yet to be fully understood. In this work, we fabricate sc-PMMA nanorods using anodic aluminum oxide (AAO) templates with various pore sizes to gain a fundamental understanding of sc-PMMA in confined states. A scanning electron microscope (SEM), a differential scanning calorimeter (DSC), and an X-ray diffractometer (XRD) are used to examine their morphologies, crystallization kinetics, and crystal characteristics. We discover that the crystallization kinetics of sc-PMMA inside the nanopores is significantly different from the bulk state. Also, the preferred orientation of sc-PMMA crystallites is mainly governed by the degree of spatial confinement and the polymer molecular weight. This work provides a deeper understanding of sc-PMMA under nanoconfinement and presents opportunities for the applications of supramolecular nanostructures in miniaturized devices.

This work proposes a mini-LED driving circuit that adopts the pulse-width modulation (PWM) driving method for use in a liquid-crystal display (LCD) backlight. The proposed circuit can compensate for the threshold voltage ( $\text{V}_{\mathrm{ TH}}$ ) variation in a low-temperature poly-crystalline silicon thin-film transistor (LTPS TFT) and a VSS current-resistance (I-R) rise, to generate a stable driving current to power the mini-LED. Since the proposed circuit uses the PWM method, the mini-LED can be operated at the best luminance-efficacy point, minimizing the power consumption of the circuit. The electrical characteristic of fabricated LTPS TFTs are measured to establish a simulation model to demonstrate the feasibility of the proposed circuit. Simulation results demonstrate that the relative mini-LED current error rates are below 9% when the $\text{V}_{\mathrm{ TH}}$ varies ± 0.3 V and VSS rises by 1 V. With respect to precise control of the gray level, the time shifts of current pulses are within 11.48 us over the whole grayscale. The improvement in the power consumption of the proposed circuit is more than 21% than that of a circuit that is driven by pulse amplitude modulation.

The insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β signal pathways are both recognized as important in regulating cancer prognosis, such as the epithelial-to-mesenchymal transition (EMT) and cell invasion. However, cross-talk between these two signal pathways in glioblastoma multiforme (GBM) is still unclear. In the present study, by analyzing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE) 4412, GBM patients with higher IGF-1 levels exhibited poorer survival. Genes positively correlated with IGF-1 were enriched in EMT and TGF-β signal pathways. IGF-1 treatment enhanced mesenchymal marker expressions and GBM cell invasion. A significant positive correlation was observed for IGF-1 with TGF-β1 (TGFB1) or TGF-β receptor 2 (TGFBR2), both of which participate in TGF-β signaling and are risk genes in the GBM process. IGF-1 stimulation promoted both TGFB1 and TGFBR2 expressions. LY2157299, a TGF-β signaling inhibitor, attenuated IGF-1-enhanced GBM cell invasion and mesenchymal transition. By analyzing IGF-1-regulated microRNA (miR) profiles, miR-4286 was found to be significantly downregulated in IGF-1-treated cells and could be targeted to both TGFB1 and TGFBR2. Overexpression of miR-4286 significantly attenuated expressions of the IGF-1-mediated mesenchymal markers, TGFB1 and TGFBR2. Using kinase inhibitors, only U0126 treatment showed an inhibitory effect on IGF-1-reduced miR-4286 and IGF-1-induced TGFB1/TGFBR2 expressions, suggesting that MEK/ERK signaling is involved in the IGF-1/miR-4286/TGF-β signaling axis. Finally, our results suggested that miR-4286 might act as a tumor suppressive microRNA in inhibiting IGF-1-enhanced GBM cell invasion. In conclusion, IGF-1 is connected to TGF-β signaling in regulating the mesenchymal transition and cell invasion of GBM through inhibition of miR-4286. Our findings provide new directions and mechanisms for exploring GBM progression.

Inertial measurement unit (IMU) sensors are widely used in many wearable systems for detecting falls in real-time and reducing the risks associated with the fall in all instances of accidents. This letter presents a highly portable and comfortable IMU-sensor-based fall detection system for elderly people. Using an accelerometer and a gyroscope, the proposed system can monitor the sudden rise of the acceleration and the orientation of the user's head to detect accidental falls. When an accidental fall is detected, the proposed system transmits alarm messages to the data server via the wireless network. Also, a complementary filter is adopted to eliminate the instability and drift of angular measurement by the accelerometer and the gyroscope, respectively. The functionality of the proposed system is verified in experiments that involve 120 falling and 450 nonfalling actions of five participants. The experimental results indicate that the proposed system achieves a fall detection accuracy of 95.44% and has the potential to assist in the everyday healthcare of elderly people.

An insufficient oxygen supply within the intratumoral environment, also known as hypoxia, induces glioblastoma multiforme (GBM) invasion, stemness, and temozolomide (TMZ) drug resistance. Long noncoding (lnc)RNAs have been reported to be involved in hypoxia and GBM progression. However, their roles in hypoxic GBM malignancy are still unclear. We investigated the mechanisms of hypoxia-mediated lncRNAs in regulating GBM processes. Using The Cancer Genome Atlas (TCGA) and data mining, hypoxia-correlated lncRNAs were identified. A hypoxia-upregulated lncRNA, MIR210HG, locating in nuclear regions, predicted poor prognoses of patients and modulated hypoxia-promoted glioma stemness, TMZ resistance, and invasion. Depletion of hypoxic MIR210HG suppressed GBM and patient-derived cell growth and increased TMZ sensitivity in vitro and vivo. Using RNA sequencing and gene set enrichment analysis (GSEA), MIR210HG-upregulated genes significantly belonged to the targets of octamer transcription factor 1 (OCT1) transcription factor. The direct interaction between OCT1 and MIR210HG was also validated. Two well-established worse prognostic factors of GBM, insulin-like growth factor-binding protein 2 (IGFBP2) and fibroblast growth factor receptor 1 (FGFR1), were identified as downstream targets of OCT1 through MIR210HG mediation in hypoxia. Consequently, the lncRNA MIR210HG is upregulated by hypoxia and interacts with OCT1 for modulating hypoxic GBM, leading to poor prognoses. These findings might provide a better understanding in functions of hypoxia/MIR210HG signaling for regulating GBM malignancy.

Lin28 is a pluripotency factor that regulates cancer cell stem-like phenotypes to promote cancer development and therapy-resistant tumor progression. It acts through its cold shock domain and zinc knuckle domain (ZKD) to interact with the Let-7 pre-microRNA and block Let-7 biosynthesis. Chemical inhibition of Lin28 from interacting with Let-7 presents a therapeutic strategy for cancer therapy. Herein, we present the computer-aided development of small molecules by in silico screening 18 million compounds from the ZINC20 library, followed by the biological validation of 163 predicted compounds to confirm 15 new Lin28 inhibitors. We report three lead compounds, Ln7, Ln15, and Ln115, that target the ZKD of both Lin28A and Lin28B isoforms and block Lin28 from binding Let-7. They restore Let-7 expression and suppress tumor oncogenes such as SOX2 in cancer cells and show strong inhibitory effects on cancer cell stem-like phenotypes. However, minimal impacts of these compounds were observed on Lin28-negative cells, confirming the on-target effects of these compounds. We conclude from this study the discovery of several new Lin28 inhibitors as promising candidate compounds that warrant further drug development into potential anticancer therapies.

The power electronics industry is now facing the higher power density design challenge to keep size shrunken but still meet the strict requirement for electromagnetic compatibility regulation. In this study, we investigated the conducted emission from a high-efficiency and compact size ac-dc switching power adaptor with flyback converter topology, and analyzed the root cause of EMI problem to further apply mitigation techniques for achieving regulation compliance. We first performed conduction emission test to obtain the emission profile for later result comparison and validation, and then utilized the ANSYS Simplorer and Q3D simulation tools to establish the analysis model for the fly-back switching power adaptor. After the simulation of the power module model being validated for effectiveness, we finally implemented the filtering scheme and PCB layout modification to effectively reduce the conducted noise and meet the product standard requirement.

The micro-grid power system is a world-wide trend for green energy demanding as part of smart-grid, and the most popular solar-cell inverter is possible suffering the surge transient disturbance from connected power system. This study investigates the electromagnetic model establishment for surge transient immunity protection analysis with ANSYS simulation tool. We first verify the simulated output of surge generator meets the waveform requirement for IEC61 000-4-5, and then investigate the possible scheme for circuit protection with proper TVS devices and placement location. We also try to investigate the possible intruding surge monitoring mechanism by analyzing the spectrum characteristics via coupling device for power system alarm implementation.

Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the β values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine.

Composite polymer electrolytes (CPEs) with smart, stimuli-responsive characteristics have gained considerable attention owing to their noninvasive manipulation and applications in future technologies. To address this potential, in this work, we demonstrate photoresponsive composite polymer electrolytes, consisting of gel polymer electrolyte (GPE) and spiropyran-immobilized nanoporous anodic aluminum oxide (SP-AAO) templates. Under UV irradiation, the close SP form isomerizes to the open merocyanine (MC) form, creating extremely polarized AAO surfaces; whereas, under visible light irradiation, the MC form reverts to the SP form, creating neutral surface conditions. The electrostatic interactions between ions and AAO surfaces are investigated by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. Moreover, the behavior of ionic conductivity of the GPE@SP-AAO is found to be consistent with the kinetics of isomerization tracked by UV-Vis spectroscopy. This work provides a promising platform for developing next-generation photoelectronic smart devices.

Cannabinoid receptor 1 (CB1) is a potential therapeutic target for the treatment of pain, obesity and obesity-related metabolic disorders, and addiction. The crystal structure of human CB1 has been determined in complex with the stabilizing antagonist AM6538. In the present study, we characterize AM6538 as a tight-binding/irreversible antagonist of CB1, as well as two derivatives of AM6538 (AM4112 and AM6542) as slowly dissociating CB1 antagonists across binding simulations and cellular signaling assays. The long-lasting nature of AM6538 was explored in vivo wherein AM6538 continues to block CP55,940-mediated behaviors in mice up to 5 days after a single injection. In contrast, the effects of SR141716A abate in mice 2 days after injection. These studies demonstrate the functional outcome of CB1 antagonist modification and open the path for development of long-lasting CB1 antagonists.

It has been demonstrated that opioid agonists that preferentially act at μ-opioid receptors to activate G protein signaling over βarrestin2 recruitment produce antinociception with less respiratory suppression. However, most of the adverse effects associated with opioid therapeutics are realized after extended dosing. Therefore, we tested the onset of tolerance and dependence, and assessed for neurochemical changes associated with prolonged treatment with the biased agonist SR-17018. When chronically administered to mice, SR-17018 does not lead to hot plate antinociceptive tolerance, receptor desensitization in periaqueductal gray, nor a super-sensitization of adenylyl cyclase in the striatum, which are hallmarks of opioid neuronal adaptations that are seen with morphine. Interestingly, substitution with SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented. This is in contrast to buprenorphine, which can suppress withdrawal, but produces and maintains morphine antinociceptive tolerance. Biased agonists of this nature may therefore be useful for the treatment of opioid dependence while restoring opioid antinociceptive sensitivity.

Excessive maternal high-fructose diet (HFD) during pregnancy and lactation has been reported to cause metabolic disorders in the offspring. Whether the infant’s brain metabolism is disturbed by maternal HFD is largely unknown. Brain energy metabolism is elevated dramatically during fetal and postnatal development, whereby maternal nutrition is a key factor that determines cellular metabolism. Astrocytes, a nonneuronal cell type in the brain, are considered to support the high-energy demands of neurons by supplying lactate. In this study, the effects of maternal HFD on astrocytic glucose metabolism were investigated using hippocampal primary cultures of female infants. We found that glycolytic capacity and mitochondrial respiration and electron transport chain were suppressed by maternal HFD. Mitochondrial DNA copy number and mitochondrial transcription factor A expression were suppressed by maternal HFD. Western blots and immunofluorescent images further indicated that the glucose transporter 1 was downregulated whereas the insulin receptor-α, phospho-insulin receptor substrate-1 (Y612) and the p85 subunit of phosphatidylinositide 3-kinase were upregulated in the HFD group. Pioglitazone, which is known to increase astrocytic glucose metabolism, effectively reversed the suppressed glycolysis, and lactate release was restored. Moreover, pioglitazone also normalized oxidative phosphorylation with an increase of cytosolic ATP. Together, these results suggest that maternal HFD impairs astrocytic energy metabolic pathways that were reversed by pioglitazone.

PURPOSE Although left atrial (LA) expansion index predicts cardiovascular events, its efficacy for predicting cerebral events is unknown. METHODS This study enrolled 2205 patients who had sinus rhythm after echocardiography in their first visit. LA expansion index was calculated as (Volmax -Volmin ) x100%/Volmin , where Volmax was defined as maximal LA volume and Volmin as minimal LA volume. The study endpoint was ischemic stroke. Stroke subtype was classified as cardioembolic stroke (CE), noncardioembolic stroke with determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). RESULTS Over a 10-year (mean 9.7 years) follow-up period, 128 (5.8%) participants reached endpoint, including 46 with CE, 33 with NCE, and 49 with ESUS. Regardless of stroke subtype, LA expansion index was lower in the event groups compared to the nonevent group. The lowest quartile of LA expansion index was associated with high CHA2 DS2 -VASc score at enrollment and more events, including CE, ESUS, atrial fibrillation (AF), heart failure, and all-cause mortality, relative to other quartiles. The LA expansion index was an independent predictor of CE (HR 0.82; 95% CI 0.723-0.912, per 10% increase in LA expansion index; P

Background T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* Methods ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4–7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. Results While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* Conclusion Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2*

Additional file 11: Figures S6. Negative correlation of lncRNA-MYC activity pairs.

Additional file 13: Figures S8. All the high resolution images in the result section.

Additional file 7: Figures S3. Stratification of patients into different clusters by a consensus clustering analysis.

Additional file 2: Figures S1. Consensus cumulative distribution function (CDF) and delta area for five cancer types.

Additional file 12: Figures S7. Positive correlation of lncRNA-MYC activity pairs.

Additional file 6: Figures S2. Flowchart for filtering cancer types and selecting glycolysis-associated long non-coding (lnc) RNAs.

Additional file 10: Figures S5. Flow chart for Transcription factor activity analyses.

Additional file 9: Figures S4. Flow chart for establishing genomic classifiers.

Background: In this study, it was shown that the routine use of McGrath videolaryngoscopy may improve intubation success rates. The benefits to using a videolaryngoscope in nasotracheal intubation were also demonstrated. However, no solid evidence concerning the effectiveness of the use of McGrath videolaryngoscopes in nasotracheal intubation has previously been reported. As a result, we questioned whether, in adult patients who underwent oral and maxillofacial surgeries with nasotracheal intubation (P), the use of a McGrath videolaryngoscope (I) compared with a Macintosh laryngoscope (C) could reduce the intubation time, improve glottis visualization to a score of classification 1 in the Cormack–Lehane classification system, and improve the first-attempt success rate (O). The secondary outcomes measured were the rate of the use of Magill forceps and the external laryngeal pressure (BURP) maneuver used. Methods: An extensive literature search was conducted using databases. Only randomized controlled trials that compared the McGrath videolaryngoscopy and Macintosh laryngoscopy techniques in nasotracheal intubation in adult patients were included. Results: Five articles met the inclusion criteria and were included in the final analysis (n = 331 patients). The results showed a significant decrease in intubation time and a higher rate of classification 1 scores in the Cormack–Lehane classification system, but no difference in the first-attempt success rates were found between the McGrath group and the Macintosh group. Decreases in the rate of the use of Magill forceps and the use of the external laryngeal pressure maneuver were also found in the pooled analysis. With regard to the overall risk of bias, the selected trials were classified to have at least a moderate risk of bias, because none of the trials could blind the operator to the type of laryngoscope used. Conclusions: Our analysis suggests that the use of a McGrath videolaryngoscope in nasotracheal intubation resulted in shorter intubation times, improved views of the glottis and similar first-success rates in adult patients who received general anesthesia for dental, oral, maxillofacial, or head and neck cancer surgery, and also reduced the use of Magill forceps and the BURP maneuver.

It is a challenge to predict the long-term future data from time series data. This paper proposes to use a Transformer with soft dynamic time wrapping for early stopping criteria, called a soft-DTW Transformer. Our experiment in an open-source dataset HouseTwenty shows that the average prediction error rate with soft-DTW Transformer is 27.79%, greatly reduced from 45.70% for using SVR, a common time series method.

Background Long noncoding (lnc)RNAs and glycolysis are both recognized as key regulators of cancers. Some lncRNAs are also reportedly involved in regulating glycolysis metabolism. However, glycolysis-associated lncRNA signatures and their clinical relevance in cancers remain unclear. We investigated the roles of glycolysis-associated lncRNAs in cancers. Methods Glycolysis scores and glycolysis-associated lncRNA signatures were established using a single-sample gene set enrichment analysis (GSEA) of The Cancer Genome Atlas pan-cancer data. Consensus clustering assays and genomic classifiers were used to stratify patient subtypes and for validation. Fisher’s exact test was performed to investigate genomic mutations and molecular subtypes. A differentially expressed gene analysis, with GSEA, transcription factor (TF) activity scoring, cellular distributions, and immune cell infiltration, was conducted to explore the functions of glycolysis-associated lncRNAs. Results Glycolysis-associated lncRNA signatures across 33 cancer types were generated and used to stratify patients into distinct clusters. Patients in cluster 3 had high glycolysis scores and poor survival, especially in bladder carcinoma, low-grade gliomas, mesotheliomas, pancreatic adenocarcinomas, and uveal melanomas. The clinical significance of lncRNA-defined groups was validated using external datasets and genomic classifiers. Gene mutations, molecular subtypes associated with poor prognoses, TFs, oncogenic signaling such as the epithelial-to-mesenchymal transition (EMT), and high immune cell infiltration demonstrated significant associations with cluster 3 patients. Furthermore, five lncRNAs, namely MIR4435-2HG, AC078846.1, AL157392.3, AP001273.1, and RAD51-AS1, exhibited significant correlations with glycolysis across the five cancers. Except MIR4435-2HG, the lncRNAs were distributed in nuclei. MIR4435-2HG was connected to glycolysis, EMT, and immune infiltrations in cancers. Conclusions We identified a subgroup of cancer patients stratified by glycolysis-associated lncRNAs with poor prognoses, high immune infiltration, and EMT activation, thus providing new directions for cancer therapy.

This paper describes the utilization of ANSYS Designer with measurement validation to provide tool for analyzing, predicting and optimizing the EFT Burst transient noise suppression implementation and effectiveness to meet the requirement of IEC61000-4-4 [1] (EFT/B). In addition, the paper describes how electromagnetic simulations can provide chip-level immunity analysis for IEC 62215-3 [2]. The analysis of residual transient noise energy from transient noise suppressing devices can also provide significant benefits to EMS protection from chip, module, and all the way to board and system level. This study intends to provide an efficient simulation model to help electronic engineers enhancing their product design reliability.

Background Although computed tomography (CT) is a powerful diagnostic imaging modality for diagnosing vascular diseases, it is some what risky to human health due to the high radiation dosage. Thus, CT vendors have developed low dose computed tomography (LDCT) aiming to solve this problem. Nowadays, LDCT has gradually become a main stream of CT examination. Objective This study aimed to assess the feasibility of LDCTAin an animal model and compare the imaging features and doses in two clinical scanners. Methods Twenty-two New Zealand rabbit head and neck CTA images pre- and post-contrast agent injection were performed using256-sliceand 64-slice CT scanners. The tube voltages used in the 256-slice and the 64-slice CTA were 70 kVp and 80 kVp, respectively. Quantitative images indices and radiation doses obtained from CTA in these two scanners were compared. Results More neck arterial vessels could be visualized in multi-planar reconstruction (MPR) CTA on the 256-slice CT scanner than on the 64-slice CT scanner. After contrast agent injection, all observed neck arterial vessels had higher CT numbers in 256-slice CTA than in 64-slice CTA. There was no significant difference in contrast-to-noise (CNR) of CTA images between these two scanners. CT dose index (CTDI) and dose length product (DLP) for the 256-slice CTA were lower than those for the 64-slice CTA. Conclusions Low dose CTA of rabbits with 70 or 80 kVp is feasible in a 256-slice or a 64-slice CT scanner. The radiation dose from the 256-slice CTA was much lower than that from the 64-slice CTA with comparable SNR and CNR. The technique can be further applied in longitudinal monitoring of an animal stroke model in the future.

DNA damage-inducible transcript 4 (DDIT4) is known to participate in various cancers, including glioblastoma multiforme (GBM). However, contradictory roles of DDIT4 exist in inducing cell death and possessing anti-apoptotic functions against cancer progression. Herein, we investigated DDIT4 signaling in GBM and temozolomide (TMZ) drug resistance. We identified that TMZ induced DDIT4 upregulation, leading to desensitization against TMZ cytotoxicity in GBM cells. Higher DDIT4 levels were found in glioma cells and mesenchymal-type GBM patients, and these higher levels were positively correlated with mesenchymal markers. Furthermore, patients with lower DDIT4 levels, especially O-6-methylguanine-DNA methyltransferase (MGMT)-methylated patients, exhibited better TMZ therapeutic efficacy. We determined that higher levels of 5 DDIT4-associated downstream genes, including SLC2A3 (also known as glucose transporter 3 (GLUT3)), can be used to predict a poor prognosis. Among these 5 genes, only GLUT3 was upregulated in both TMZ-treated and DDIT4-overexpressing cells. DDIT4-mediated GLUT3 expression was also identified, and its expression decreased TMZ’s cytotoxicity. A significant correlation existed between DDIT4 and GLUT3. DDIT4 signaling was found to be involved in both glycolytic and autophagic pathways. However, GLUT3 only participated in the exhibition of DDIT4-mediated stemness, resulting from glycolytic regulation, but not in DDIT4-mediated autophagic signaling. Finally, we identified TMZ-upregulated activating transcription factor 4 (ATF4) as an upstream regulator of DDIT4-mediated GLUT3/stemness signaling and autophagy. Consequently, ATF4/DDIT4 signaling was connected to both autophagy and GLUT3-regulated stemness, which are involved in TMZ drug resistance and the poor prognoses of GBM patients. Targeting DDIT4/GLUT3 signaling might be a new direction for glioma therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-019-00826-0) contains supplementary material, which is available to authorized users.

Imatinib (IM) is a first-line therapeutic drug for chronic myeloid leukemia (CML), a hematological disease. Mutations in the BCR-ABL domain increase formation of IM resistance in CML. However, not all patients are BCR-ABL domain-mutant dependent. Investigating non-mutant mechanisms in the development of acquired IM resistance is a critical issue. We explored the mechanisms which influence IM efficacy and resistance in CML. Higher protective autophagy was identified in IM-resistant K562 (K562R) cells. Inhibition of autophagy by the inhibitors, chloroquine and 3-methyladenine, enhanced IM's efficacy in K562R cells. In addition, microRNA (miR)-199a/b-5p were downregulated in K562R cells compared to parent cells. Overexpression of miR-199a/b-5p reduced autophagy and induced cell apoptosis, resulting in enhanced IM's efficacy in K562R cells. Moreover, expression levels of the Wingless-type MMTV integration site family member 2 (WNT2), a positive regulator of autophagy, were significantly higher in K562R cells, and it was validated as a direct target gene of miR-199a/b-5p. Overexpressions of miR-199a/b-5p inhibited WNT2 downstream signaling. Furthermore, overexpression and knockdown of WNT2 influenced autophagy formation and CML drug sensitivity to IM. Overexpression of WNT2 could also reverse miR-199a/b-5p-enhanced IM efficacy in K562R cells. These results emphasized that miR-199a/b-5p inhibited autophagy via repressing WNT2 signaling and might provide novel therapeutic strategies for future IM-resistant CML therapy and drug development.