Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.

BACKGROUND: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children. AIMS: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients. METHODS: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range. RESULTS: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose. CONCLUSION: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

The floating body effect of a WSe2 transistor with volatile memory performance.

The floating body effect in Meta-Stable-Dip RAM (MSDRAM) has been broadly employed in implementing single-transistor capacitor-less (1T0C) dynamic random access memory (DRAM) cells to break through the limitation of finite size reduction of peripheral capacitors. However, the majority of them were broadly demonstrated in conventional CMOS technology, while emerging semiconductor systems are rarely explored. Here, we creatively explore exfoliated multilayer tungsten diselenide (WSe2) for the application of 1T0C DRAM, breaking the limitation of channel thickness in the traditional architecture. Through the comparison of the electrical characteristics among three dual-gate transistors with different lengths of top-gate, we demonstrated the essential role of the floating body effect in achieving the function of 1T0C DRAM displaying two distinct states that are differentiated by hole population within the floating body. Moreover, according to the analysis of in situ electrostatic force microscopy (EFM) measurements and theoretical calculation via density functional theory (DFT), the injection of holes through band-to-band (B2B) tunneling can be ascribed to the effectively electrostatic modulation. These consequences prove our innovative concept to achieve the function of 1T0C DRAM through employing the ML WSe2, which is a vital step toward the breakthrough of the inherent limitations of DRAM cells.

A van der Waals Integrated Damage-Free Memristor Based on Layered 2D Hexagonal Boron Nitride.

2D materials with intriguing properties have been widely used in optoelectronics. However, electronic devices suffered from structural damage due to the ultrathin materials and uncontrolled defects at interfaces upon metallization, which hindered the development of reliable devices. Here, a damage-free Au/h-BN/Au memristor is reported using a clean, water-assisted metal transfer approach by physically assembling Au electrodes onto the layered h-BN which minimized the structural damage and undesired interfacial defects. The memristors demonstrate significantly improved performance with the coexistence of nonpolar and threshold switching as well as tunable current levels by controlling the compliance current, compared with devices with evaporated contacts. The devices integrated into an array show suppressed sneak path current and can work as both logic gates and latches to implement logic operations allowing in-memory computing. Cross-sectional scanning transmission electron microscopy analysis validates the feasibility of this nondestructive metal integration approach, the crucial role of high-quality atomically sharp interface in resistive switching, and a direct observation of percolation path. The underlying mechanism of boron vacancies-assisted transport is further supported experimentally by conductive atomic force microscopy free from process-induced damage, and theoretically by ab initio simulations.

[Effect of moxibustion on renal function and hypercoagulable state in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis].

OBJECTIVE: To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis. METHODS: A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups. RESULTS: The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (P<0.05). On 3 and 6 months into treatment, the total TCM syndrome scores were decreased compared before treatment in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). On 3 months into treatment, the levels of UTP, FIB, D-D, P-selection and vWF were decreased (P<0.05), the level of ALB was increased (P<0.05) compared before treatment in the observation group; the levels of UTP and FIB were decreased compared before treatment in the control group (P<0.05); the level of ALB in the observation group was higher than that in the control group (P<0.05), the levels of FIB and vWF in the observation group were lower than those in the control group (P<0.05). On 6 months into treatment, the levels of UTP, FIB, D-D, P-selection, vWF, TC and TG were decreased (P<0.05), the levels of ALB were increased (P<0.05) compared before treatment in the both groups (P<0.05); the levels of UTP, FIB, D-D, P-selection, vWF, TC and TG in the observation group were lower than those in the control group, the level of ALB in the observation group was higher than that in the control group (P<0.05). CONCLUSION: Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

Neuromorphic Engineering: From Biological to Spike-Based Hardware Nervous Systems.

The human brain is a sophisticated, high-performance biocomputer that processes multiple complex tasks in parallel with high efficiency and remarkably low power consumption. Scientists have long been pursuing an artificial intelligence (AI) that can rival the human brain. Spiking neural networks based on neuromorphic computing platforms simulate the architecture and information processing of the intelligent brain, providing new insights for building AIs. The rapid development of materials engineering, device physics, chip integration, and neuroscience has led to exciting progress in neuromorphic computing with the goal of overcoming the von Neumann bottleneck. Herein, fundamental knowledge related to the structures and working principles of neurons and synapses of the biological nervous system is reviewed. An overview is then provided on the development of neuromorphic hardware systems, from artificial synapses and neurons to spike-based neuromorphic computing platforms. It is hoped that this review will shed new light on the evolution of brain-like computing.

Recent advances in synthesis and application of perovskite quantum dot based composites for photonics, electronics and sensors.

In recent years, halide perovskite quantum dots (HP-QDs) based composites have been widely developed and used in various applications owing to their unique photonic, electronic and mechanical properties, as well as high stability to water, oxygen, heat and illumination. Remarkable efforts have been made in the synthesis and applications of these materials in photonics, electronics, sensors and other fields. Besides these topics, we also cover enhancement of optoelectronic properties as well as chemical, thermal and photostability of HP-QDs-based composites. We hope this review will promote both the development and applications of perovskite-based materials.

Type-I Core-Shell ZnSe/ZnS Quantum Dot-Based Resistive Switching for Implementing Algorithm.

Core-shell semiconductor quantum dots (QDs) are one of the biggest nanotechnology successes so far. In particular, type-I QDs with straddling band offset possess the ability to enhance the charge carriers capturing which is useful for memory application. Here, the type-I core-shell QD-based bipolar resistive switching (RS) memory with anomalous multiple SET and RESET processes was demonstrated. The synergy and competition between space charge limited current conduction (arising from charge trapping in potential well of type-I QDs) and electrochemical metallization (ECM, originating from redox reaction of Ag electrode) process were employed for modulating the RS behavior. Through utilizing stochastic RS mechanisms in QD-based devices, four situations of RS behaviors can be classified into three states in Markov chain for implementing the application of a true random number generator. Furthermore, a 6 × 6 cross-bar array was demonstrated to realize the generation of random letters with case distinction.

A UV damage-sensing nociceptive device for bionic applications.

Artificial limbs have been widely investigated in the past several decades, and multifuncional bionic limbs have already been constructed. However, due the lack of nociceptive systems, amputees still cannot feel ubiquitous noxious stimuli through bionic limbs. The construction of artificial nociceptors can bring bionic limbs closer to real flesh and bone. In daily life, UV irradiation is an invisible potential noxious stimulus to human skin and eyes. Furthermore, it is well known that the synthetic polymers widely used in bionic limbs can be degraded by UV radiation, accelerating their aging. Based on the above, UV damage-sensing nociceptors could be a feasible strategy to solve these existing problems. Here, azobenzene-functionalized gold nanoparticles (Azo-Au NPs) are embedded in insulating poly(methyl methacrylate) (PMMA) to construct a two-terminal memristor. With UV irradiation as a light damage medium, major nociceptive behaviors such as "threshold", "relaxation" and "sensitization" are successfully emulated, demonstrating its potential application as a nociceptive system.

Biological Spiking Synapse Constructed from Solution Processed Bimetal Core-Shell Nanoparticle Based Composites.

Inspired by the highly parallel processing power and low energy consumption of the biological nervous system, the development of a neuromorphic computing paradigm to mimic brain-like behaviors with electronic components based artificial synapses may play key roles to eliminate the von Neumann bottleneck. Random resistive access memory (RRAM) is suitable for artificial synapse due to its tunable bidirectional switching behavior. In this work, a biological spiking synapse is developed with solution processed Au@Ag core-shell nanoparticle (NP)-based RRAM. The device shows highly controllable bistable resistive switching behavior due to the favorable Ag ions migration and filament formation in the composite film, and the good charge trapping and transport property of Au@Ag NPs. Moreover, comprehensive synaptic functions of biosynapse including paired-pulse depression, paired-pulse facilitation, post-tetanic potentiation, spike-time-dependent plasticity, and the transformation from short-term plasticity to long-term plasticity are emulated. This work demonstrates that the solution processed bimetal core-shell nanoparticle-based biological spiking synapse provides great potential for the further creation of a neuromorphic computing system.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Increases the Yield of Transbronchial Lung Biopsy for the Evaluation of Peribronchial Lesions.

BACKGROUND: Due to absence of visible endobronchial target, the diagnostic yield of flexible bronchoscopy for peribronchial lesions has been unsatisfactory. Convex probe endobronchial ultrasound (CP-EBUS) has allowed for performing real-time transbronchial needle aspiration (TBNA) of enlarged hilar and mediastinal lymph nodes and therefore could also be used as a means of diagnosing proximal peribronchial lesions. METHODS: We retrospectively analyzed the results related to 72 patients who underwent CP-EBUS for peribronchial lesions without endobronchial involvement and adjacent to three-grade bronchi based on chest computed tomography (CT) scan. We recorded the images during EBUS as well as the diagnostic results of TBNA and conventional-transbronchial lung biopsy/brush (C-TBLB/b), and final diagnoses were based on pathologic analysis and follow-up. RESULTS: In all cases, the mass was able to be identified using EBUS in 97.2% patients (70/72) who were performed with EBUS-TBNA + C-TBLB/b. Sixty-six patients had a final diagnosis, 80.0% patients (56/70) had malignancies, and 14.3% patients (10/70) had benign disease. In malignancies, the diagnostic yield of C-TBLB/b was 57.1% (32/56) and in EBUS-TBNA was 85.7% (48/56), whereas pathologic diagnosis reached 94.6% when EBUS-TBNA was combined with C-TBLB/b. C-TBLB/b + EBUS-TBNA also exhibited stronger potency of histolytic diagnosis for malignancies than either EBUS-TBNA or C-TBLB/b alone. Furthermore, there are data supporting the value of EBUS-TBNA for the diagnosis of benign lung disease. CONCLUSION: The combined endoscopic approach with EBUS-TBNA and C-TBLB/b is an accurate and effective method for the evaluation of peribronchial lesions, with better results than using each technique alone.

Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions: Six cases reports and review of literature.

BACKGROUND: Patients with isolated mediastinal or hilar lymphadenopathy, or peribronchial lesions, are common presentation to clinicians. Due to the difficulty in tissue sampling, the pathological diagnosis is not so easy. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established, highly effective, minimally invasive technique for sampling. The current study was conducted to investigate the value of EBUS-TBNA in patients of solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions. METHODS: Six patients with different pathological results diagnosed via EBUS-TBNA were retrospectively analyzed in this study. RESULTS: All 6 patients of solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions underwent conventional flexible bronchoscopy before EBUS-TBNA, but only EBUS-TBNA was helpful for the finally definite diagnosis. No complication was observed. CONCLUSION: EBUS-TBNA is a safe and highly effective diagnostic procedure for both benign and malignant diseases, especially for patients with solitary mediastinal, hilar lymphadenectasis, or peribronchial lesions.

Braun enteroenterostomy reduces delayed gastric emptying: A systematic review and meta-analysis.

BACKGROUND: It remains controversial whether the additional Braun enteroenterostomy (BEE) is necessary in decreasing delayed gastric emptying (DGE) following pancreaticoduodenectomy (PD). This meta-analysis aims to assess the efficacy of the additional BEE in reducing DGE after PD. METHODS: PubMed, EMBASE, Science Citation Index and The Cochrane Library were searched to identify relevant studies. Articles published before May 15, 2015 comparing BEE with traditional gastrojejunostomy during PD were selected. The evaluated end points consist of intro-operative outcomes as well as postoperative complications. RESULTS: Seven observational clinical studies that recruited 1401 patients were included. This meta-analysis indicated that the occurrence of DGE was lower in Braun group (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.15 to 0.60; P = 0.0007). Overall morbidity (OR, 0.61; 95%CI, 0.47 to 0.80; P = 0.0003) and the length of hospital stay (LOS) (weighted mean difference [WMD], -1.80; 95%CI, -3.4 to -0.18; p = 0.03) were also in favor of the Braun group. However, Braun group had no advantage over Non-Braun group in terms of intra-operative blood loss, mortality, pancreatic fistula, bile Leakage and intra-abdominal abscess. CONCLUSION: The additional of BEE plays an important role in reducing DGE, overall morbidity and LOS.

MicroRNA-215 is upregulated by treatment with Adriamycin and leads to the chemoresistance of hepatocellular carcinoma cells and tissues.

Non-coding microRNAs (miRNAs), involved in post-transcriptional control, are widely involved in the mechanism of cellular resistance to antitumor chemotherapy. Ectopic expression of one of these miRNAs, miRNA­215 (miR­215), leads to chemoresistance by directly targeting dihydrofolate reductase (DHFR) and thymidylate synthase (TS), which are two of the most important targets of chemotherapeutic agents. This indicates the possible upregulation of endogenous miR­215 in the process of chemoresistance by interfering with important transcripts. In the present study, the upregulation of miR­215 was examined in hepatocellular carcinoma (HCC) subcell lines, Adriamycin (ADM)­resistant HepG2 (HepG2/AR), Hep3B (Hep3B/AR) cell lines, and in ADM­treated patients with HCC. Upregulated miR­215 directly targeted DHFR and TS mRNA and reduced their protein expression levels, without altering mRNA levels. The ectopic expression of miR­215 anti­sense oligo­nucleotides in HepG2/AR and Hep3B/AR cells enhanced chemosensitivity, whereas the expression of the miR­215 mimics led to chemoresistance. Notably, the upregulation of miR­215 indirectly increased the protein levels of P53 and P21 levels in the HepG2 cells, which contain functional P53, which is expected to result in the inhibition of proliferation and colony formation. Taken together, the present study demonstrated that the upregulation of miR­215 resulting from ADM treatment in HCC cells leads to the development of insensitivity to ADM and worsens the prognosis of patients with HCC exhibiting mutated P53.