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Introduction: The major complication of aspirin and clopidogrel (A+C) co-therapy is upper gastrointestinal bleeding (UGIB). However, data are unavailable for real-life situations. Furthermore, the treatment effect of antisecretory agents is unknown. Aim: This cohort study aimed to determine the occurrence of UGIB. The treatment effect of H2-receptor antagonist (H2RA) and proton pump inhibitor (PPI) was also analyzed. Method: The records of 987 consecutive patients on A+C co-therapy between January 2001 and September 2006 were analyzed. The follow-up ended on the dates of a first occurrence of UGIB, stopping A+C co-therapy, a change in the antisecretory class, death, or March 2007. Results: After a follow-up of 5.8 ± 6.5 months, UGIB occurred in 39 (4.0%) patients. PPI, H2RA and control were prescribed in 213, 287 and 487 patients respectively. After adjustment for age, dose of aspirin, previous UGIB and duration of treatment, the risk was marginally reduced by H2RA (OR = 0.43, 95% CI 0.18–0.91, p = 0.04) and significantly reduced by PPI (OR = 0.04, 95% CI 0.002–0.21, p = 0.002), as compared to control. Conclusion: The occurrence of UGIB associated with A+C co-therapy for a median of 5.8 months was 4.0%. Co-prescription with PPI was associated with a lower risk. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

BACKGROUND: The combination of aspirin, clopidogrel, and enoxaparin (combination therapy) is the standard treatment for acute coronary syndrome but is associated with gastrointestinal bleeding. However, information in this area is scarce. AIM: This retrospective study aimed to determine the incidence of upper gastrointestinal bleeding in a real-life situation. The effect of proton pump inhibitor (PPI) treatment was also analyzed. METHOD: From January 2002 to December 2006, all patients receiving combination therapy were analyzed. The end point was the occurrence of upper gastrointestinal bleeding during combination therapy or within 7 days of stopping enoxaparin. RESULTS: The patient group consisted of 666 patients (age 72.1 ± 12.6 yr). Gastrointestinal bleeding occurred in 18 (2.7%) patients. The overall hospital mortality was 4.1% (27 patients). A cardiac event was the major cause (N = 24, 3.6%). Only one patient died of massive gastrointestinal bleeding (0.15%). Multiple logistic regression analysis demonstrated that previous peptic ulcer, cardiogenic shock, and the lack of PPI coprescription were significant risk factors for gastrointestinal bleeding. The age-adjusted odds ratio (95% confidence interval) for gastrointestinal bleeding was 5.07 (1.31–16.58) for previous peptic ulcer, 21.41 (2.56–146.68) for cardiogenic shock, and 0.068 (0.010–0.272) for the coprescription with a PPI. CONCLUSION: In real life, the incidence of gastrointestinal bleeding associated with the combination of aspirin, clopidogrel, and enoxaparin therapy was estimated to be 2.7%. Previous peptic ulcer disease or cardiogenic shock were significant independent risk factors. Coprescription with a PPI can significantly reduce the risk. [ABSTRACT FROM AUTHOR]

Familial transthyretin amyloidosis (ATTR), caused by mutant transthyretin deposition, is mainly characterized by peripheral neuropathy, autonomic dysfunction, and cardiomyopathy. There are few reports among the Chinese population. We previously described the TTR mutation (Val30Ala) in the first Hong Kong Chinese family with ATTR. In this study, we report the progress of this family and describe another three unrelated Chinese kinships newly diagnosed with ATTR. The second proband presented mainly with peripheral neuropathy, and genetic analysis of the TTR gene showed alanine-to-serine substitution at amino acid 97. The third proband complained of autonomic dysfunction, and a novel missense mutation of glycine-to-glutamate substitution at amino acid 67 was found. The fourth patient presented with peripheral neuropathy and diastolic cardiomyopathy with the mutation threonine-to-lysine at codon 59. Diagnosis was delayed for more than 2 years. We performed DNA analysis in 46 subjects and detected a total of 21 patients, including the four probands, affected with ATTR, 15 of whom were still at a symptom-free stage at the time of writing. We conclude that ATTR remains largely underdiagnosed in the Chinese population. A high clinical suspicion is crucial for a timely diagnosis and can thus lead to a significant decrease in morbidity and mortality. [ABSTRACT FROM AUTHOR]

Due to the relatively low efficiency of magnetic hyperthermia and photothermal conversion, it is rather challenging for magneto-photothermal nanoagents to be used as an effective treatment during tumor hyperthermal therapy. The advancement of magnetic nanoparticles exhibiting a vortex-domain structure holds great promise as a viable strategy to enhance the application performance of conventional magnetic nanoparticles while retaining their inherent biocompatibility. Here, we report the development of Mn 0.5 Zn 0.5 Fe 2 O 4 nanoflowers with ellipsoidal magnetic cores, and show them as effective nanoagents for magneto-photothermal synergistic therapy. Comparative studies were conducted on the heating performance of anisometric Mn 0.5 Zn 0.5 Fe 2 O 4 (MZF) nanoparticles, including nanocubes (MZF-C), hollow spheres (MZF-HS), nanoflowers consisting of ellipsoidal magnetic cores (MZF-NFE), and nanoflowers consisting of needle-like magnetic cores (MZF-NFN). MZF-NFE exhibits an intrinsic loss parameter (ILP) of up to 15.3 N h m 2 kg -1 , which is better than that of commercial equivalents. Micromagnetic simulations reveal the magnetization configurations and reversal characteristics of the various MZF shapes. Additionally, all nanostructures displayed a considerable photothermal conversion efficiency rate of more than 18%. Our results demonstrated that by combining the dual exposure of MHT and PTT for hyperthermia treatments induced by MZF-NFE, BT549, MCF-7, and 4T1 cell viability can be significantly decreased by ∼95.7% in vitro .

Memristors are essential components of neuromorphic systems that mimic the synaptic plasticity observed in biological neurons. In this study, a novel approach employing one-dimensional covalent organic framework (1D COF) films was explored to enhance the performance of memristors. The unique structural and electronic properties of two 1D COF films (COF-4,4'-methylenedianiline (MDA) and COF-4,4'-oxydianiline (ODA)) offer advantages for multilevel resistive switching, which is a key feature in neuromorphic computing applications. By further introducing a TiO 2 layer on the COF-ODA film, a built-in electric field between the COF-TiO 2 interfaces could be generated, demonstrating the feasibility of utilizing COFs as a platform for constructing memristors with tunable resistive states. The 1D nanochannels of these COF structures contributed to the efficient modulation of electrical conductance, enabling precise control over synaptic weights in neuromorphic circuits. This study also investigated the potential of these COF-based memristors to achieve energy-efficient and high-density memory devices., (© 2024 Wiley-VCH GmbH.)

Hardware neural networks with mechanical flexibility are promising next-generation computing systems for smart wearable electronics. Overcoming the challenge of developing a fully synaptic plastic network, we demonstrate a low-operating-voltage PET/ITO/p-MXene/Ag flexible memristor device by controlling the etching of aluminum metal ions in Ti 3 C 2 T x MXene. The presence of a small fraction of Al ions in partially etched MXene (p-Ti 3 C 2 T x ) significantly suppresses the operating voltage to 1 V compared to 7 V from fully Al etched MXene (f-Ti 3 C 2 T x )-based devices. Former devices exhibit excellent non-volatile data storage properties, with a robust ∼10 3 ON/OFF ratio, high endurance of ∼10 4 cycles, multilevel resistance states, and long data retention measured up to ∼10 6 s. High mechanical stability up to ∼73° bending angle and environmental robustness are confirmed with consistent switching characteristics under increasing temperature and humid conditions. Furthermore, a p-Ti 3 C 2 T x MXene memristor is employed to mimic the biological synapse by measuring the learning-forgetting pattern for ∼10 4 cycles as potentiation and depression. Spike time-dependent plasticity (STDP) based on Hebb's Learning rules is also successfully demonstrated. Moreover, a remarkable accuracy of ∼95% in recognizing modified patterns from the National Institute of Standards and Technology (MNIST) data set with just 29 training epochs is achieved in simulation. Ultimately, our findings underscore the potential of MXene-based flexible memristor devices as versatile components for data storage and neuromorphic computing.

Neuromorphic platforms are gaining popularity due to their superior efficiency, low power consumption, and adaptable parallel signal processing capabilities, overcoming the limitations of traditional von Neumann architecture. We conduct an in-depth investigation into the factors influencing the resistive switching mechanism in memristor devices utilizing lead iodide (PbI 2 ). We establish correlations between device performance and morphological features, unveiling synaptic like behaviour of device making it suitable for range of flexible neuromorphic applications. Notably, a highly reliable unipolar switching mechanism is identified, exhibiting stability even under mechanical strain (with a bending radius of approximately 4 mm) and in high humidity environment (at 75% relative humidity) without the need for encapsulation. The investigation delves into the complex interplay of charge transport, ion migration and the active interface, elucidating the factors contributing to the remarkable resistive switching observed in PbI 2 -based memristors. The detailed findings highlight synaptic behaviors akin to the modulation of synaptic strengths, with an impressive potentiation and depression of 2 × 10 4 cycles, emphasizing the role of spike time-dependent plasticity (STDP). The flexible platform demonstrates exceptional performance, achieving a simulated accuracy rate of 95.06% in recognizing modified patterns from the National Institute of Standards and Technology (MNIST) dataset with just 30 training epochs. Ultimately, this research underscores the potential of PbI 2 -based flexible memristor devices as versatile component for neuromorphic computing. Moreover, it demonstrate the robustness of PbI 2 memristors in terms of their resistive switching capabilities, showcasing resilience both mechanically and electrically. This underscores their potential in replicating synaptic functions for advanced information processing systems.

Conventional magnetic nanoagents in cancer hyperthermia therapy suffer from a low magnetic heating efficiency. To address this issue, researchers have pursued magnetic nanoparticles with topological magnetic domain structures, such as the vortex-domain structure, to enhance the magnetic heating performance of conventional nanoparticles while maintaining excellent biocompatibility. In this study, we synthesized hollow spherical Mn 0.5 Zn 0.5 Fe 2 O 4 (MZF-HS) nanoparticles using a straightforward solvothermal method, yielding samples with an average outer diameter of approximately 350 nm and an average inner diameter of about 220 nm. The heating efficiency of the nanoparticles was experimentally verified, and the specific absorption rate (SAR) value of the hollow MZF was found to be approximately 1.5 times that of solid MZF. The enhanced heating performance is attributed to the vortex states in the hollow MZF structure as validated with micromagnetic simulation studies. In vitro studies demonstrated the lower cell viability of breast cancer cells (MCF-7, BT549, and 4T1) after MHT in the presence of MZF-HS. The synthesized MZF caused 51% cell death after MHT, while samples of MZF-HS resulted in 77% cell death. Our findings reveal that magnetic particles with a vortex state demonstrate superior heating efficiency, highlighting the potential of hollow spherical particles as effective heat generators for MHT applications.

Due to their significant resemblance to the biological brain, spiking neural networks (SNNs) show promise in handling spatiotemporal information with high time and energy efficiency. Two-terminal memristors have the capability to achieve both synaptic and neuronal functions; however, such memristors face asynchronous programming/reading operation issues. Here, a three-terminal memristor (3TM) based on oxygen ion migration is developed to function as both a synapse and a neuron. We demonstrate short-term plasticity such as pair-pulse facilitation and high-pass dynamic filtering in our devices. Additionally, a 'learning-forgetting-relearning' behavior is successfully mimicked, with lower power required for the relearning process than the first learning. Furthermore, by leveraging the short-term dynamics, the leaky-integrate-and-fire neuronal model is emulated by the 3TM without adopting an external capacitor to obtain the leakage property. The proposed bi-functional 3TM offers more process compatibility for integrating synaptic and neuronal components in the hardware implementation of an SNN.

The use of crystalline metal-organic complexes with definite structures as multilevel memories can enable explicit structure-property correlations, which is significant for designing the next generation of memories. Here, four Zn-polysulfide complexes with different degrees of conjugation have been fabricated as memory devices. ZnS 6 (L) 2 -based memories (L = pyridine and 3-methylpyridine) can exhibit only bipolar binary memory performances, but ZnS 6 (L)-based memories (L = 2,2'-bipyridine and 1,10-phenanthroline) illustrate non-volatile ternary memory performances with high ON2/ON1/OFF ratios (10 4.22 /10 2.27 /1 and 10 4.85 /10 2.58 /1) and ternary yields (74% and 78%). Their ON1 states stem from the packing adjustments of organic ligands upon the injection of carriers, and the ON2 states are a result of the ring-to-chain relaxation of S 6 2- anions. The lower conjugated degrees in ZnS 6 (L) 2 result in less compact packing; consequently, the adjacent S 6 2- rings are too long to trigger the S 6 2- relaxation. The deep structure-property correlation in this work provides a new strategy for implementing multilevel memory by triggering polysulfide relaxation based on the conjugated degree regulation of organic ligands.

Emerging technologies, i.e., spintronics, 2D materials, and memristive devices, have been widely investigated as the building block of neuromorphic computing systems. Three-terminal memristor (3TM) is specifically designed to mitigate the challenges encountered by its two-terminal counterpart as it can concurrently execute signal transmission and memory operations. In this work, we present a complementary metal-oxide-semiconductor-compatible 3TM with highly linear weight update characteristics and a dynamic range of ∼15. The switching mechanism is governed by the migration of oxygen ions and protons in and out of the channel under an external gate electric field. The involvement of the protonic defects in the electrochemical reactions is proposed based on the bipolar pulse trains required to initiate the oxidation process and the device electrical characteristics under different humidity levels. For the synaptic operation, an excellent endurance performance with over 256k synaptic weight updates was demonstrated while maintaining a stable dynamic range. Additionally, the synaptic performance of the 3TM is simulated and implemented into a four-layer neural network (NN) model, achieving an accuracy of ∼92% in MNIST handwritten digit recognition. With such desirable conductance modulation characteristics, our proposed 3T-memristor is a promising synaptic device candidate to realize the hardware implementation of the artificial NN.

The readout margin of the one selector-one RRAM crossbar array architecture is strongly dependent on the nonlinearity of the selector device. In this work, we demonstrated that the nonlinearity of Pt/TiO 2 /Pt exponential selectors increases with decreasing oxygen vacancy defect density. The defect density is controlled by modulating the sputtering pressure in the oxide deposition process. Our results reveal that the dominant conduction mechanisms of the Pt/TiO 2 /Pt structure transit from Schottky emission to Poole-Frenkel emission with the increase of sputtering pressure. Such transition is attributed to the rise of oxygen vacancy concentration. In addition, the short-term plasticity feature of the Pt/TiO 2 /Pt selector is shown to be enhanced with a lower defect density. These results suggest that low defect density is necessary for improved exponential selector performances., (© 2023 IOP Publishing Ltd.)

Short-term plasticity (STP) is an important synaptic characteristic in the hardware implementation of artificial neural networks (ANN), as it enables the temporal information processing (TIP) capability. However, the STP feature is rather challenging to reproduce from a single nonvolatile resistive random-access memory (RRAM) element, as it requires a certain degree of volatility. In this work, a Pt/TiO x /Pt exponential selector is introduced not only to suppress the sneak current but also to enable the TIP feature in a one selector-one RRAM (1S1R) synaptic device. Our measurements reveal that the exponential selector exhibits the STP characteristic, while a Pt/HfO x /Ti RRAM enables the long-term memory capability of the synapse. Thereafter, we experimentally demonstrated pulse frequency-dependent multilevel switching in the 1S1R device, exhibiting the TIP capability of the developed 1S1R synapse. The observed STP of the selector is strongly influenced by the bottom metal-oxide interface, in which Ar plasma treatment on the bottom Pt electrode resulted in the annihilation of the STP feature in the selector. A mechanism is thus proposed to explain the observed STP, using the local electric field enhancement induced at the metal-oxide interface coupled with the drift-diffusion model of mobile O 2- and Ti 3+ ions. This work therefore provides a reliable means of producing the STP feature in a 1S1R device, which demonstrates the TIP capability sought after in hardware-based ANN.

Background: At present, the majority of outcome studies of survival of hepatocellular carcinoma (HCC) post-liver resection (post-LR) present actuarial survival data, which often results in overestimation of survival. We sought to evaluate the actual 10-year survival post-LR for HCC and identify variables that are associated with long-term survival., Methods: We performed a retrospective review of 600 consecutive patients who underwent primary LR for HCC from 2000 to 2010 at our institution. Twenty-eight patients (4.7%) with 90-day mortality and 125 patients who were lost to follow-up within 10 years were excluded leaving 447 patients who met the study criteria., Results: There were 140 actual 10-year survivors of which 57 (40.7%) had a recurrence within 10 years. The actual 10-year overall survival (OS) rate of the 447 patients was 31.5% and the actual 10-year recurrence-free survival (RFS) was 18.6%. Multivariate analyses demonstrated that only age >65 years (OR, 0.29; p < .001) (OR, 0.973; p = .041) and presence of cirrhosis (OR. 0.37; p = .005) (OR, 0.31; p = .001) were independent factors negatively associated with actual 10-year OS and actual 10-year RFS, respectively., Conclusion: Approximately one-third of patients will survive over 10 years after LR for HCC. Amongst these 10-year survivors, 41% had developed recurrent cancer within 10-years of follow-up., (© 2020 Wiley Periodicals LLC.)

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of nonsmall cell lung cancer (NSCLC) predominantly reported in East Asia. We aimed to evaluate clinical characteristics, diagnosis, treatment, and prognosis of PPLELC in Singapore., Methods: Retrospective review of all patients diagnosed with PPLELC at our center between 2000 and 2014., Results: All 28 patients were Chinese, 67.9% were female, and the median age was 58 years (range37-76 years). Majority (89.3%) were never smokers and 53.6% asymptomatic at diagnosis. About 28.6% presented with Stage I/II disease, 25% had Stage III disease, and 46.4% had Stage IV disease. All patients with Stage I/II disease underwent lobectomy without adjuvant treatment. Four out of 7 patients with Stage III disease underwent surgery with or without adjuvant therapy while the rest received chemoradiation. Twelve out of 13 patients with Stage IV disease received chemotherapy with or without radiotherapy. At the end of 2016, survival data were available for all 28 patients. Two-year survival rates for Stage I/II, Stage III, and Stage IV disease were 100%, 85.7%, and 61.5%, respectively, while survival was 100%, 85.7%, and 9.6%, respectively, at five years., Conclusion: The majority (46.4%) of patients presented with metastatic disease. For those with Stage I-III disease, 5-year survival for PPLELC was better than other NSCLC subtypes. Multimodality treatment including surgery could be considered in locally advanced disease. In Stage IV disease, it tended to approximate that of NSCLC., Competing Interests: There are no conflicts of interest.

Purpose: To compare clinical outcomes of anterior cruciate ligament (ACL) reconstruction and investigate whether the clinical results of 4-strand hamstring tendon (HT) reconstruction are still inferior to that of the patellar tendon (PT)., Methods: We performed a comprehensive systematic review and meta-analysis of the English literature on PubMed, Scopus, Web of Science, and the Cochrane register for papers that compared clinical outcomes of PT versus HT for ACL reconstruction. Outcome measures analyzed included rate of rerupture, KT-1000, International Knee Documentation Committee grade, Lachman, pivot shift, Lysholm score, Tegner Activity Scale, anterior knee pain, and discomfort on kneeling., Results: We included 19 studies from an initial 1,168 abstracts for the systematic review, and, eventually, 19 studies were included in the meta-analysis. The study population consisted of a total of 1784 patients. The average follow-up duration was 58.8 months. We found significant differences in favor of the HT technique in the domains of anterior knee pain, kneeling pain, and restriction in the range of active extension ("extension deficit"). We found no differences between the PT and HT technique in terms of rerupture rate. There were no clinically significant differences for the outcomes of Lysholm score and Tegner Activity Scale as well as the KT-1000 side-to-side at maximum manual force., Conclusions: Contemporary 4-strand HT ACL reconstruction is comparable with the PT technique in terms of clinical stability and postoperative functional status across most parameters studied. The HT technique carries lower risk of postoperative complications such as anterior knee pain, kneeling discomfort, and extension deficit. Primary ACL reconstruction using the 4-strand HT technique achieves clinical results that are comparable with the PT technique with significantly less postoperative complications., Level of Evidence: Level I, systemic review and meta-analysis of Level I studies., (Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: To demonstrate whether the regional recurrence (RR) of squamous cell carcinoma (SCC) of the nasal cavity is higher than previously suspected., Data Sources: Original articles, including a previously published series from our institution, were identified from systematic searches of the MEDLINE database., Study Selection: Studies that analyzed tumors other than SCC or tumors from sites other than the nasal cavity were excluded. Studies that did not report an RR were also excluded., Data Extraction: Studies identified by the literature search were reviewed by a single reviewer (W.C.S.), and studies not excluded were reviewed for data extraction by 2 reviewers (W.C.S. and M.Y.C.)., Data Synthesis: From the 23 studies reviewed, the average weighted percentage RR for SCC of the nasal cavity was 18.1% (95% confidence interval, 13.4%-22.8%)., Conclusions: Currently, few authors advocate elective treatment of the neck in patients with high-risk SCC of the nasal cavity. The results of this systematic review and meta-analysis demonstrate that the RR of this entity may be higher than previously suspected. Because many studies included other histopathologies or analyzed recurrence data from tumors of multiple subsites, a true RR for SCC of the nasal cavity has not been firmly established. Now that a uniform staging system exists for nasal cavity cancers, better prospective analysis of these tumors will be available. The authors suggest that the risk of RR of certain high-risk SCCs of the nasal cavity to the lymph nodes, including the perifacial and upper cervical lymphatics, may approach the frequently cited 20% risk suggestive of consideration for elective regional therapy.