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Abstract Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival for prolonged cardiac arrest (CA) but carries significant risks and costs due to ECMO. Previous predictive models have been complex, incorporating both clinical data and parameters obtained after CPR or ECMO initiation. This study aims to compare a simpler clinical-only model with a model that includes both clinical and pre-ECMO laboratory parameters, to refine patient selection and improve ECPR outcomes. Medical records between January 2012 and January 2019 in our institution were retrospectively reviewed. Patients who met the following criteria were enrolled in the ECPR program: age 18–75 years, CCPR started with CA in

Abstract Background Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. Methods The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. Results Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3′untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3′UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. Conclusions These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Abstract Background The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined. Methods Short hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model. Results Nicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression. Conclusion Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.

Abstract Background Refractory cardiac arrest resistant to conventional cardiopulmonary resuscitation (C-CPR) has a poor outcome. Although previous reports showed that extracorporeal cardiopulmonary resuscitation (E-CPR) can improve the clinical outcome, there are no clinically applicable predictors of patient outcome that can be used prior to the implementation of E-CPR. We aimed to evaluate the use of clinical factors in patients with refractory cardiac arrest undergoing E-CPR to predict patient outcome in our institution. Methods This is a single-center retrospective study. We report 112 patients presenting with refractory cardiac arrest resistant to C-CPR between January 2012 and November 2017. All patients received E-CPR for continued life support when a cardiogenic etiology was presumed. Clinical factors associated with patient outcome were analyzed. Significant pre-ECMO clinical factors were extracted to build a patient outcome risk prediction model. Results The overall survival rate at discharge was 40.2, and 30.4% of patients were discharged with good neurologic function. The six-month survival rate after hospital discharge was 36.6, and 25.9% of patients had good neurologic function 6 months after discharge. We stratified the patients into low-risk (n = 38), medium-risk (n = 47), and high-risk groups (n = 27) according to the TLR score (low-flow Time, cardiac arrest Location, and initial cardiac arrest Rhythm) that we derived from pre-ECMO clinical parameters. Compared with the medium-risk and high-risk groups, the low-risk group had better survival at discharge (65.8% vs. 42.6% vs. 0%, p

AimsDiabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM).MethodsKtrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).ResultsIn all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs.ConclusionsThis study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

A graphite-based RRAM device with a self-rectifying characteristic named “non-linearity (NL)” is developed for a high-density crossbar array for in-memory computing with low power and high scalability. Meanwhile, the reprogrammable functions are presented in self-selected RRAM as a promising candidate for one-time programmable (OTP) in the emerging memory-embedded applications such as security, system-on-chip (SoC), and Internet of Things (IoT).

An amendment to this paper has been published and can be accessed via the original article.

In this study, a direct-grown helical-shaped tungsten-oxide-based (h-WOx) selection device is presented for emerging memory applications. The selectivity in the selection devices is from 10 to 103 with a low off-current of 0.1 to 0.01 nA. In addition, the selectivity of volatile switching in the h-WOx selection devices is reconfigurable with a pseudo RESET process on the one-time negative voltage operations. The helical-shaped selection devices with the glancing angle deposition (GLAD) method show good compatibility, low power consumption, good selectivity, and good reconfigurability for next-generation memory applications.

The ever‐increasing processing power demands of digital computers cannot continue to be fulfilled indefinitely unless there is a paradigm shift in computing. Neuromorphic computing, which takes inspiration from the highly parallel, low‐power, high‐speed, and noise‐tolerant computing capabilities of the brain, may provide such a shift. Many researchers from across academia and industry have been studying materials, devices, circuits, and systems, to implement some of the functions of networks of neurons and synapses to develop neuromorphic computing platforms. These platforms are being designed using various hardware technologies, including the well‐established complementary metal‐oxide semiconductor (CMOS), and emerging memristive technologies such as SiOx‐based memristors. Herein, recent progress in CMOS, SiOx‐based memristive, and mixed CMOS‐memristive hardware for neuromorphic systems is highlighted. New and published results from various devices are provided that are developed to replicate selected functions of neurons, synapses, and simple spiking networks. It is shown that the CMOS and memristive devices are assembled in different neuromorphic learning platforms to perform simple cognitive tasks such as classification of spike rate‐based patterns or handwritten digits. Herein, it is envisioned that what is demonstrated is useful to the unconventional computing research community by providing insights into advances in neuromorphic hardware technologies.

Abstract This letter presents dual functions including selector and memory switching in a V/SiO x /AlO y /p++Si resistive memory device by simply controlling compliance current limit (CCL). Unidirectional threshold switching is observed after a positive forming with low CCL of 1 μA. The shifts to the V-electrode side of the oxygen form the VO x layer, where the threshold switching can be explained by the metal-insulation-transition phenomenon. For higher CCL (30 μA) applied to the device, a bipolar memory switching is obtained, which is attributed to formation and rupture of the conducting filament in SiO y layer. 1.5-nm-thick AlO y layer with high thermal conductivity plays an important role in lowering the off-current for memory and threshold switching. Through the temperature dependence, high-energy barrier (0.463 eV) in the LRS is confirmed, which can cause nonlinearity in a low-resistance state. The smaller the CCL, the higher the nonlinearity, which provides a larger array size in the cross-point array. The coexistence of memory and threshold switching in accordance with the CCL provides the flexibility to control the device for its intended use.

Abstract Complex hydrogels formed with chitosan (CS) and ring-opened polyvinyl pyrrolidone (roPVP) as a swellable mucoadhesive gastroretentive drug dosage form (smGRDDF) were prepared and characterized. CS/roPVP hydrogels were produced by blending CS with roPVP obtained by basic treatment of PVP. Effects of the heating time and NaOH concentration employed for preparing roPVP, and CS molecular weights (Mws), and roPVP/CS ratios on the swelling ability of the resultant hydrogels were characterized. Rheological characteristics were further examined. Results demonstrated that roPVP obtained in a 0.5 M NaOH solution heated to 50 °C for 4 h was suitable for producing complex hydrogels with CS. At a roPVP/CS ratio of 20:1, hydrogels composed of three different Mws of CS possessed optimal swelling and mucoadhesive abilities and rheological properties. In vitro dissolution revealed sustained drug release. A pharmacokinetic study exhibited that the plasma profile of alendronate followed a sustained manner with 3-fold enhancement of the oral bioavailability. In conclusion, the smGRDDF composed of CS/roPVP complex hydrogels was successfully developed and is potentially applicable to improve the clinical efficacy of bisphosphonates.

In this work, the nonlinear (NL) characteristics of bi-layer high-k/low-k dielectrics structure, i.e. high-k layer with the low-k layer, are for selectorless oxide-based resistive random-access memories (RRAM) memory array application. It has been shown that such structure enhances the read currents at full read voltage (∼10-3 A) as compared to the bi-layer low-k/low-k structure (∼10-4 A), reduces low-voltage current, increases I-V nonlinearity and thereby suppresses the sneak path currents in the selectorless RRAM. Improved seasoning effect has also been demonstrated using the bilayer dielectric structure. The Fowler-Nordheim tunneling behavior has been found in the first RESET process (-0.45 to -1.25 V) as followed by the high self-rectifying characteristics that enlarge the immunity to the sneak path current and reduce the read errors in the array applications. The breakdown controllability of the forming process dominates the followed seasoning cycles which leads to two different performances in bilayer stacks i.e. efficient seasoning and inefficient seasoning, which provides an intrinsic design of selectorless RRAM devices. The device characteristics with current transport mechanisms have also been investigated. Our results provide additional insights into ways to achieve high performance and excellent reliability of built-in nonlinearity in selectorless RRAM (NL > 120, memory window > 100, sub-μs switching speed, and NL retention) for the future low-power RRAM memory array configurations.

Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial–mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer.

The sneak path current (SPC) is the inevitable issue in crossbar memory array while implementing high-density storage configuration. The crosstalks are attracting much attention, and the read accuracy in the crossbar architecture is deteriorated by the SPC. In this work, the sneak path current problem is observed and investigated by the electrical experimental measurements in the crossbar array structure with the half-read scheme. The read margin of the selected cell is improved by the bilayer stacked structure, and the sneak path current is reduced ~20% in the bilayer structure. The voltage-read stress-induced read margin degradation has also been investigated, and less voltage stress degradation is showed in bilayer structure due to the intrinsic nonlinearity. The oxide-based bilayer stacked resistive random access memory (RRAM) is presented to offer immunity toward sneak path currents in high-density memory integrations when implementing the future high-density storage and in-memory computing applications.

Function generators are vital tools for many industrial applications. Sinusoidal oscillators are the essential units of function generators and investigating their performance is therefore necessary. The Barkhausen criterion is widely applied in designing sinusoidal oscillators because of its simplicity. The authors exploit a crucial necessary and sufficient oscillation criterion for Wien Bridge and Colpitts oscillators based on Simple Chen's Electric Unifying Approach. Their approach resolves the shortcoming of the traditional Barkhausen criterion, namely that it entails only a necessary condition. They propose a simple oscillation determining criterion that uses a stable sine-wave oscillator with an adjustable oscillation frequency. The derived oscillation criterion establishes a precise condition for the existence of oscillatory behaviour and does not require the fixed value used in the traditional Barkhausen criterion. To demonstrate its applicability, the proposed approach for the Wien Bridge and Colpitts oscillators is applied to implement a function generator.

There has been considerable interest in the biological functions of astaxanthin and its potential applications in the nutraceutical, cosmetics, food, and feed industries in recent years. However, the unstable structure of astaxanthin considerably limits its application. Therefore, this study reports the encapsulation of astaxanthin in calcium alginate beads using the extrusion method to improve its stability. This study also evaluates the stability of the encapsulated astaxanthin under different storage conditions. The evaluation of astaxanthin stability under various environmental factors reveals that temperature is the most influential environmental factor in astaxanthin degradation. Stability analysis shows that, regardless of the formulation used, the content of astaxanthin encapsulated in alginate beads remains above 90% of the original amount after 21 days of storage at 25°C. These results suggest that the proposed technique is a promising way to enhance the stability of other sensitive compounds.

PURPOSE:This meta-analysis examined roles of several metabolites in differentiating recurrent tumor from necrosis in patients with brain tumors using MR perfusion and spectroscopy. METHODS:Medline, Cochrane, EMBASE, and Google Scholar were searched for studies using perfusion MRI and/or MR spectroscopy published up to March 4, 2015 which differentiated between recurrent tumor vs. necrosis in patients with primary brain tumors or brain metastasis. Only two-armed, prospective or retrospective studies were included. A meta-analysis was performed on the difference in relative cerebral blood volume (rCBV), ratios of choline/creatine (Cho/Cr) and/or choline/N-acetyl aspartate (Cho/NAA) between participants undergoing MRI evaluation. A χ2-based test of homogeneity was performed using Cochran's Q statistic and I2. RESULTS:Of 397 patients in 13 studies who were analyzed, the majority had tumor recurrence. As there was evidence of heterogeneity among 10 of the studies which used rCBV for evaluation (Q statistic = 31.634, I2 = 97.11%, P < 0.0001) a random-effects analysis was applied. The pooled difference in means (2.18, 95%CI = 0.85 to 3.50) indicated that the average rCBV in a contrast-enhancing lesion was significantly higher in tumor recurrence compared with radiation injury (P = 0.001). Based on a fixed-effect model of analysis encompassing the six studies which used Cho/Cr ratios for evaluation (Q statistic = 8.388, I2 = 40.39%, P = 0.137), the pooled difference in means (0.77, 95%CI = 0.57 to 0.98) of the average Cho/Cr ratio was significantly higher in tumor recurrence than in tumor necrosis (P = 0.001). There was significant difference in ratios of Cho to NAA between recurrent tumor and necrosis (1.02, 95%CI = 0.03 to 2.00, P = 0.044). CONCLUSIONS:MR spectroscopy and MR perfusion using Cho/NAA and Cho/Cr ratios and rCBV may increase the accuracy of differentiating necrosis from recurrent tumor in patients with primary brain tumors or metastases.

Nanocarrier-based delivery systems are promising strategies for enhanced therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)—a light-triggered chemical reaction that generates localized tissue damage for disease treatments—usually has side effects, and thus patients receiving photosensitizers should be kept away from direct light to avoid skin phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225) was conjugated to the surface of methoxy poly(ethylene glycol)-b-poly(lactide) (mPEG-b-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6-loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing A431 cells observed by confocal laser scanning microscopy (CLSM), thereby decreasing the IC50 value of Ce6-mediated PDT from 0.42 to 0.173 μM. No significant differences were observed in cellular uptake study or IC50 value between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of tumor growth inhibition, TGI% = 84.8) were significantly smaller than those in the Ce6-PDT (TGI% = 38.4) and Ce6/PM-PDT groups (TGI% = 53.3) (p < 0.05) at day 21 through reduced cell proliferation in A431 xenografted mice. These results indicated that active EGFR targeting of photosensitizer-loaded micelles provides a possible way to resolve the dose-limiting toxicity of conventional photosensitizers and represents a potential delivery system for PDT in a clinical setting.

A mycelial mattress of Rhizopus stolonifer obtained from a liquid static culture was utilized for wound dressing and biomedical use. Following screening of mutants induced by UV radiation, F6, exhibiting delayed sporangium formation was selected because its sporangium maturation exhibited a 5-day delay without significant loss of mycelial weight compared to the wild type. The sporangium-free mycelial mattress from the sporangiospore culture of F6 was treated with 1N sodium hydroxide NaOH at 85°C for 2 h to produce a sponge-like membrane named Rhizochitin. The trifluoroacetic acid hydrolysate of Rhizochitin contained 36% N-acetylglucosamine and 53% hexose respectively detected by the Elson-Morgen and phenol-sulfuric acid methods. Results indicated the wound area in rats covered with Rhizochitin was 40% less than that of the uncovered group. Rhizochitin decreased the expression of PDGF in the proliferation stage, increased the expression of TGF-β in the inflammation and proliferation stages, and increased the expression of VEGF in the inflammation and proliferation stages. Rhizochitin inhibited secretion of matrix metalloproteinase-9 on days 1, 7, 9, and 12 and matrix metalloproteinase-2 on days 3, 7, 9, and 12. It was concluded that Rhizochitin has beneficial properties of biocompatible, biodegradable, and wound healing.

The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug's release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics.

Effervescent multiple-unit floating drug delivery systems (muFDDSs) consisting of drug (lorsartan)- and effervescent (sodium bicarbonate)-containing pellets were characterized in this study. The mechanical properties (stress and strain at rupture, Young's modulus, and toughness) of these plasticized polymeric films of acrylic (Eudragit RS, RL, and NE) and cellulosic materials (ethyl cellulose (EC), and Surelease) were examined by a dynamic mechanical analyzer. Results demonstrated that polymeric films prepared from Surelease and EC were brittle with less elongation compared to acrylic films. Eudragit NE films were very flexible in both the dry and wet states. Because plasticizer leached from polymeric films during exposure to the aqueous medium, plasticization of wet Eudragit RS and RL films with 15% triethyl citrate (TEC) or diethyl phthalate (DEP) resulted in less elongation. DEP might be the plasticizer of choice among the plasticizers examined in this study for Eudragit RL to provide muFDDSs with a short time for all pellets to float (TPF) and a longer period of floating. Eudragit RL and RS at a 1∶1 ratio plasticized with 15% DEP were optimally selected as the coating membrane for the floating system. Although the release of losartan from the pellets was still too fast as a result of losartan being freely soluble in water, muFDDSs coated with Eudragit RL and RS at a 1∶1 ratio might have potential use for the sustained release of water-insoluble or the un-ionized form of drugs from gastroretentive drug delivery systems.

Global influenza surveillance is one of the most effective strategies for containing outbreaks and preparing for a possible pandemic influenza. Since the end of 2003, highly pathogenic avian influenza viruses (HPAI) H5N1 have caused many outbreaks in poultries and wild birds from East Asia and have spread to at least 48 countries. For such a fast and wide-spreading virulent pathogen, prediction based on changes of micro- and macro-environment has rarely been evaluated. In this study, we are developing a new climatic approach by investigating the conditions that occurred before the H5N1 avian influenza outbreaks for early predicting future HPAI outbreaks and preventing pandemic disasters. The results show a temperature drop shortly before these outbreaks in birds in each of the Eurasian regions stricken in 2005 and 2006. Dust storms, like those that struck near China's Lake Qinghai around May 4, 2005, exacerbated the spread of this HPAI H5N1 virus, causing the deaths of a record number of wild birds and triggering the subsequent spread of H5N1. Weather monitoring could play an important role in the early warning of outbreaks of this potentially dangerous virus.