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Remarkable Li-ion battery(LIB) anode materials need to have long cycle life and fast charge/discharge rate, however they are difficult to be realized in the monolayer anode materials. The monolayer β-Bi has the stiffness of only 33.0 N/m, thus the Bi/G heterostructure is proposed to improve the electronic and mechanical properties and to produce better LIB anode performance in this paper. The calculated results show that Bi/G heterostructure has excellent thermodynamic, dynamical and mechanical stability. The band gap is only 0.04 eV, which ensures remarkable electrical conductivity. In addition, the Bi/G heterostructure has higher stiffness (369.2 N/m) than that of monolayer β-Bi and graphene. The diffusion barrier (Ebarrier) of 0.32 eV and volume expansion ratio(VER) of only 4% can ensure the rapid transport of Li+ ions in the charge/discharge cycling process and long life of the LIB. These calculated theoretical results for describing the detail properties of Li storage and diffusion in the Bi/G heterostructure can supply adequate conclusive evidence for the prediction of remarkable properties of Bi/G heterostructure as an anode material for LIBs.

Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

To evaluate the correlation between structural parameters and visual acuity (VA) in advanced glaucoma.Prospective, cross-sectional study.A total of 238 eyes from 238 patients (82 were men and mean ± SD age was 59.9 ± 13.8 years) from a tertiary center were divided into an advanced (mean deviation of 24-2 visual field tests from -12.01 to -20.0 dB) and severe (-20 dB) glaucoma group. Structural parameters were obtained by RTVue (Optovue Inc) optical coherence tomography and angiography. Pearson correlation, partial correlation adjusted for age and axial length, and receiver operating characteristic curves to detect decreased VA (20/25) were performed.In the advanced glaucoma group (133 eyes), superficial (Pearson correlation coefficient, r = -0.46, P.001; partial correlation coefficient, r' = -0.30, P.001) and deep macular vessel densities (VDs) (r = -0.47, P.001; r' = -0.30, P.001) showed highest correlation with VA. The area under the receiver operating characteristic curves of the superficial parafoveal/macular VDs were 0.816 (95% CI, 0.735-0.897) and 0.808 (95% CI, 0.725-0.891), respectively. In the severe glaucoma group (105 eyes), deep nasal grid VD (r = -0.31, P = 0.002; r' = -0.35, P.001) showed highest correlation with VA. Deep macular VD showed better correlation with VA than other structural parameters. The area under the receiver operating characteristic curves of deep macular VD and deep nasal grid VD were 0.740 (95% CI, 0.632-0.849) and 0.748 (95% CI, 0.640-0.857), respectively.Macular VD showed better correlation with VA in advanced glaucoma. Deep macular VD, especially nasal grid, may be a promising structural parameter in severe glaucoma.

B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy (BCMA CAR-T) is an effective treatment of relapsed refractory multiple myeloma (MM). However, the pattern of infectious complications is not well elucidated. We performed a single-center retrospective analysis of infection outcomes up to 1 year after BCMA CAR-T for MM from 2018 to 2020. Fifty-five patients with MM were treated with BCMA CAR-T. Before lymphodepletion (LD), 35% of patients had severe hypogammaglobulinemia and 18% had severe lymphopenia. Most patients (68%) received bridging chemotherapy (BC) before LD. In the first month after CAR-T, 98% patients had grade 3 to 4 neutropenia. At 1 year after infusion, 76% patients had hypogammaglobulinemia. With a median follow-up of 6.0 months (95% confidence interval, 4.7-7.4), there were a total of 47 infection events in 29 (53%) patients: 40% bacterial, 53% viral, and 6% fungal. Most (92%) were mild-moderate and of the lower/upper respiratory tract system (68%). Half of the infections (53%) occurred in the first 100 days after CAR-T infusion. Although no statistically significant risk factors for infection were identified, prior lines of therapy, use of BC, recent infections, and post–CAR-T lymphopenia were identified as possible risk factors that need to be further explored. This is the largest study to date to assess infectious complications after BCMA CAR-T. Despite multiple risk factors for severe immunosuppression in this cohort, relatively few life-threatening or severe infections occurred. Further larger studies are needed to better characterize the risk factors for and occurrence of infections after BCMA CAR-T.

Purpose : The association between visual impairment (VI) and the risk of dementia has been poorly understood. We sought to investigate the VI-dementia relationship in the UK Biobank Study. Design : Prospective cohort study Methods : A total of 117,187 volunteers (aged 40-69 years) deemed free of dementia at baseline were included. Habitual distance visual acuity worse than 0.3 logMAR units in the better-seeing eye was used to define VI. The incident dementia was based on electronically linked hospital inpatient and death records. Results : During a median follow up of 5.96 years, the presence of VI was significantly associated with incident dementia (HR=1.78, 95% CI: 1.18-2.68, P=0.006). There was a clear trend between the severity of VI and the risk of dementia (P for trend=0.002). Conclusions : We found VI was associated with increased risk of dementia, with a progressively greater risk among those with worse visual acuity. Our findings suggested that visual impairment might be a modifiable risk factor for dementia and highlighted the potential value of VI elimination to delay the manifestation of dementia.

Clinically, the renin-angiotensin-aldosterone system is activated intensely in patients with moderate to severe traumatic brain injury (TBI). Increased angiotensin II in circulatory blood after TBI can enter the brain through the disrupted blood-brain barrier. Angiotensin-converting enzyme 2 (ACE2) is an enzyme that metabolizes angiotensin II into angiotensin (1-7), which has been shown to have neuroprotective results. The expression and role of ACE2 in the brain after TBI remains elusive, however. We found that ACE2 protein abundance was downregulated around the contusional area in the brains of both humans and mice. Endogenous ACE2 was expressed in neurons, astrocytes, and microglia in the cortex of the mouse brain. Administration of recombinant human ACE2 intracerebroventricularly alleviated neurological defects after TBI in mice. Treatment of recombinant human ACE2 suppressed TBI-induced increase of angiotensin II and the decrease of angiotensin (1-7) in the brain, mitigated neural cell death, reduced the activation of NLRP3 and caspase3, decreased phosphorylation of mitogen-activated protein kinases, and nuclear factor kappa B, and reduced inflammatory cytokines tumor necrosis factor alpha and interleukin-1β. Administration of ACE2 enzyme activator diminazene aceturate intraperitoneally rescued downregulation of ACE2 enzymatic activity and protein abundance in the brain. Diminazene aceturate treatment once per day in the acute stage after TBI alleviated long-term cognitive defects and neuronal loss in mice. Collectively, these results indicated that restoration of ACE2 alleviated neurological deficits after TBI by mitigation of pyroptosis and apoptosis.

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders., Graphical abstract Unlabelled Image

China began connecting farmers directly with supermarkets 10 years ago, when they were at a disadvantage and forced to sell products at low prices, as unstable cooperation among supply chain participants led to inequitable distribution of revenue. Revenue-sharing contracts offer a risk-sharing approach to ensure supply chain coordination and optimize profit for all. Research on short life cycle products with revenue-sharing contracts assume stable prices or investigate the effects of revenue-sharing contracts on supply chain coordination. This study introduced a revenue-sharing contract model into a ‘farmer-supermarket direct-purchase’ supply chain, considering price fluctuation and retail promotional efforts, stochastic market demand, among other factors. Revenue-sharing contracts achieved long-term stability in supply chain coordination, all participants obtained more profits, and the size of revenue-sharing parameter depends on the position and bargaining power of all participants. A case study on Tianhong supermarket and Nanxia farmer cooperative verified these findings, eliciting practical implications for professionals and policymakers.

This paper concerns the problem of trajectory design and base station (BS) association for cellular-connected unmanned aerial vehicles (UAVs). To support safety-critical functions, one primary requirement for UAVs is to maintain reliable cellular connectivity at every time instant during the flight mission. Since the antenna gain of a ground BS (GBS) changes with the position of the UAV, the UAV-GBS association strategy should be jointly considered with the trajectory design, which has not been studied in the prior arts. In this paper, we first formulate the problem of joint BS association and trajectory design with the objective of minimizing the mission completion time under a connectivity outage constraint. Then, a deep learning framework is proposed to solve the formulated non-convex optimization problem in a decoupled manner. For the UAV-GBS association strategy, the signal strength radio map of a given area is constructed, which is used to train a deep neural network (DNN) to approximate the nonlinear mapping from the UAV position to the optimal GBS. To tackle the high complexity due to the coupled decision variables of GBS association and UAV movement, a novel deep reinforcement learning (DRL) approach is developed to learn the optimal trajectory, in which the UAV can learn from its own past good experiences. Our simulation results confirm the superiority of the proposed DRL approach compared to the conventional DRL approaches in terms of trajectory length. Additionally, it is demonstrated that the nearest association scheme fails to provide reliable cellular connections, whereas our proposed approach can ensure strong connectivity with the GBS during the whole trajectory.

The entropy-driven monolayer assembly of hexagonal prisms and cylinders was studied under hard slit confinement. At the conditions investigated, the particles have two distinct and dynamically disconnected rotational states: unflipped and flipped, depending on whether their circular/hexagonal face is parallel or perpendicular to the wall plane. Importantly, these two rotational states cast distinct projection areas over the wall plane that favor either hexagonal or tetragonal packing. Monte Carlo simulations revealed a re-entrant melting transition where an intervening disordered Flipped-Unflipped (FUN) phase is sandwiched between a fourfold tetratic phase at high concentrations and a sixfold triangular solid at intermediate concentrations. The FUN phase contains a mixture of flipped and unflipped particles and is translationally and orientationally disordered. Complementary experiments were conducted with photolithographically fabricated cylindrical microparticles confined in a wedge cell. Both simulations and experiments show the formation of phases with comparable fraction of flipped particles and structure, i.e., the FUN phase, triangular solid, and tetratic phase, indicating that both approaches sample analogous basins of particle-orientation phase-space. The phase behavior of hexagonal prisms in a soft-repulsive wall model was also investigated to exemplify how tunable particle–wall interactions can provide an experimentally viable strategy to dynamically bridge the flipped and unflipped states.

Background Age‐related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age‐related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut–muscle axis. However, the effects and mechanisms of probiotics in age‐related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. Methods We administered LcS (1 × 108 or 1 × 109 CFU/mouse/day) by oral gavage to senescence‐accelerated mouse prone‐8 mice for 12 weeks (16‐ to 28‐week‐old). Sixteen‐week‐old and 28‐week‐old SMAP8 mice were included as non‐aged and aged controls, respectively. Muscle condition was evaluated using dual‐energy X‐ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme‐linked immunosorbent assay. Gas chromatography–mass spectrometry was utilized to measure the short‐chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. Results The LcS supplementation reduced age‐related declines in muscle mass (>94.6%, P 66% in holding impulse and >96.3% in grip strength, P 65.9% in the mice given high dose of LcS, P 89.4%, P 2.0] were positively correlated with healthy muscle and physiological condition (P 2.0) were negatively associated with healthy muscle and physiological condition (P

Prognostics predicts the future performance progression and remaining useful life (RUL) of in-service systems based on historical and contemporary data. One of the challenges in prognostics is the development of methods that are capable of handling real-world uncertainties that typically lead to inaccurate predictions. To alleviate the impacts of uncertainties and to achieve accurate degradation trajectory and RUL predictions, a novel sequence-to-sequence predictive model is proposed based on a variational autoencoder that is trained with generative adversarial networks. A long short-term memory network and a Gaussian mixture model are utilized as building blocks so that the model is capable of providing probabilistic predictions. Correlative and monotonic metrics are applied to identify sensitive features in the degradation progress, in order to reduce the uncertainty induced from raw data. Then, the selected features are concatenated with one-hot health state indicators as training data for the model to learn end of life without the need for prior knowledge of failure thresholds. Performance of the proposed model is validated by health monitoring data collected from real-world aeroengines, wind turbines, and lithium-ion batteries. The results demonstrate that significant performance improvement can be achieved in long-term degradation progress and RUL prediction tasks.

Background/purpose: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. Methods: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. Results: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9–26.2), 25.7 (24.0–27.9), and 29.1 (25.8–32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74–0.98) and 0.91 (0.79–1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4–11.2), 11.7 (11.3–12.1), 13.4 (12.5–14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p

Study objective Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. Bullae are special skin manifestations of NF. This study was conducted to analyze the differences between different types of bullae of limbs with NF for providing the information to emergency treatment. Methods From April 2015 to August 2018, patients were initially enrolled based on surgical confirmation of limbs with NF. According to the presence of different bullae types, patients were divided into no bullae group (Group N), serous-filled bullae group (Group S), and hemorrhagic bullae group (Group H). Data such as demographics, clinical outcomes, microbiological results, presenting symptoms/signs, and laboratory findings were compared among these groups. Results In total, 187 patients were collected, with 111 (59.4%) patients in Group N, 35 (18.7%) in Group S, and 41 (21.9%) in Group H. Group H had the highest incidence of amputation, required intensive care unit care, and most patients infected with Vibrio species. In Group N, more patients were infected with Staphylococcus spp. than Group H. In Group S, more patients were infected with β-hemolytic Streptococcus than Group H. Patients with bacteremia, shock, skin necrosis, anemia, and longer prothrombin time constituted higher proportions in Group H and S than in Group N. Conclusions In southern Taiwan, patients with NF accompanied by hemorrhagic bullae appear to have more bacteremia, Vibrio infection, septic shock, and risk for amputation. If the physicians at the emergency department can detect for the early signs of NF as soon as possible, and more patient’s life and limbs may be saved.

Introduction Chimeric antigen receptor (CAR) T-cells can induce a rapid disease response but are frequently associated with immunologic toxicities. In addition to cytokine release syndrome (CRS), macrophage activation syndrome-like manifestations (MAS-L), characterized by uncontrolled immune activation, have been described (Shah et al, 2020). Traditional MAS definitions are challenging to apply in patients receiving CAR T cells, due to overlapping signs and symptoms with lymphodepletion and CRS. Therefore, we sought to develop novel criteria to characterize MAS-L following CAR T cells and used these criteria to identify risk factors for developing MAS-L. Methods We conducted a retrospective review of 55 patients who received B cell maturation antigen-directed CAR T cells for multiple myeloma from 11/1/17 - 5/1/20. Based on the labs readily available in our patient population, we defined MAS-L using the following criteria: 1) rate of ferritin rise ³ 100 mg/L/hour within a 24 hour period and 2) minimum fibrinogen 2 times the upper limit of normal. In developing these simplified criteria, we considered multiple laboratory markers of inflammation (ferritin, LDH, soluble interleukin receptor-2, natural killer cell activity) and end organ damage. Infection was defined as any culture positivity, febrile neutropenia, or clinical suspicion such that a new antimicrobial was started in the 30 days prior to CAR T cells. Wilcoxon rank-sums and Fisher’s exact test were used to compare continuous and categorical variables, respectively. Overall (OS) and progression-free survival (PFS) were compared using log-rank tests. Results Of the 55 patients, 12 (21.8%) met the above criteria for MAS-L with similar disease trajectories. Following CAR T cells, all 12 patients first developed CRS, characterized by an elevated C-reactive protein (CRP) and administration of tocilizumab, and subsequently developed MAS-L, characterized by decrease in fibrinogen and rapid rise of ferritin and LDH (Figure 1). Compared to the 45 patients who did not develop MAS-L, patients with MAS-L had similar baseline patient and disease characteristics (Table 1); however, a significantly higher proportion of patients with MAS-L had an infection prior to receiving CAR T cells (75% vs 9.3%, p Compared to patients who did not develop MAS-L, a similar proportion of MAS-L patients developed any CRS (100% vs 84%, p = 0.33) and ³ grade 2 CRS (50% vs 50%, p = 1). Neurotoxicity was more common in patients with MAS-L (42% vs 14%, p = 0.05). A greater proportion of patients with MAS-L received tocilizumab (100% vs 70%, p = 0.05), systemic steroids (92% vs 27%, p Following CAR T cell therapy, patients with MAS-L had longer hospitalizations (21 vs 19 days, p = 0.009) and a greater proportion required ICU-level care (27% vs 2%, p = 0.02). OS and PFS between the two groups were similar (p = 0.15 and 0.63, respectively), with a 1-year OS of 65.2% vs 90.6% and PFS of 35.4% vs 54.7% for patients with vs without MAS-L, respectively. In univariate logistic regression of baseline patient factors, disease characteristics, and ferritin, CRP, and D-dimer prior to receiving CAR T cells, only a history of documented infection in the 30 days prior to CAR T cells predicted MAS-L development (Hazard Ratio 29.2, 95% CI 5.54 - 154, p Conclusions In this analysis, we developed novel criteria for defining MAS-L following CAR T cell therapy and used these criteria to define the unique laboratory profile and clinical trajectory of patients with MAS-L. We also identify pre-existing infection as a strong risk factor for MAS-L development. Although patients with MAS-L frequently require prolonged monitoring, this immunologic toxicity can be mitigated with steroids, anakinra, and supportive care, and patients ultimately have similar survival compared to patients without MAS-L. Larger studies are needed to prospectively validate these novel criteria. Download : Download high-res image (447KB) Download : Download full-size image Disclosures Wolf: Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martin: Sanofi, Amgen, Seattle Genetics, JNJ - Janssen: Research Funding; Legend Biotech: Consultancy. Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Wong: Bristol Myers Squibb: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Janssen: Research Funding; Roche: Research Funding; Fortis: Research Funding; GSK: Research Funding.

As a result of ongoing regional disparities, the United Network for Organ Sharing (UNOS) implemented policy in May 2019 limiting exception points for waitlisted patients with hepatocellular carcinoma (HCC) to median Model for End-Stage Liver Disease at transplant in the area surrounding a transplant center minus 3 points (MMAT-3). The impact of this policy change remains unknown. We included adult patients with HCC (n = 4567) and without HCC (n = 19,773) in the UNOS database added to the waiting list before this policy change (May 7, 2017-May 18, 2019) and after (May 19, 2019-March 7, 2020). Cumulative incidence analysis estimated the probability of dropout within 1 year of listing decreased from 12.9% before the policy to 11.1% after the policy in candidates without HCC and from 14% to 10.7% in candidates with HCC. Incidence rates of liver transplantation (LT) and waitlist dropout varied significantly before the policy in patients with HCC and without HCC but nearly equalized in the postpolicy era. These effects were observed in both shorter and longer wait regions. With policy change being modeled as a time-dependent covariate, competing risk regression analyses estimated a decreased risk of dropout after policy change in the non-HCC group (cause-specific hazard ratio, 0.91; P = 0.02) after adjusting for demographic variables. These results suggest that the MMAT-3 policy has successfully reduced disparities in access to LT including across UNOS wait regions, although certain patients with HCC are now disadvantaged.

Gradual advances have occurred in the design of micro-artificial intelligence for resource-limited hardware. A high-resolution (HR) image reconstruction module is indispensable for video analytics chips or devices at the edge. This paper proposes a low-cost and learning-based interpolation method for HR image reconstruction. The proposed method generates reconstructed pixels by processing reference pixels with optimal weights, which are pre-trained by solving the minimum mean square error problem for real images. To reduce the number of computation units and the usage of learned weights, a cross-directional interpolation architecture, which includes a vertical kernel and a horizontal kernel, is adopted. Moreover, a one-dimensional feature discriminator is proposed to improve the quality of up-scaled images efficiently. The main benefit of the proposed method is that it requires a small number of computation units but can still produce high-quality images. The hardware architecture of the proposed method was implemented on a field-programmable gate array (FPGA) by using Xilinx UltraScale+ ZCU102 and an application-specific integrated circuit (ASIC) by using TSMC’s 0.13-μm technology. On the ASIC, the proposed hardware required only approximately 60K gate counts and 50 KBytes of memory. The experimental results indicate that the average peak signal-to-noise ratio of the up-scaled images reached 35.92 dB for the Set-5 dataset. The throughput of the proposed hardware was at least 1000 Mpixels/s on the FPGA and 1200 Mpixels/s on the ASIC, which indicates that the proposed hardware can handle a target resolution higher than 4K in real time.

Software is widely used in many application domains. The most popular software are used by millions every day. How to accurately predict and assess the reliability of developed software is becoming increasingly important for project managers and developers. Previous studies have primarily used the software reliability growth model (SRGM) to evaluate and predict software reliability, but prediction results cannot be accurate at particular times or in particular situations. One of the main reasons is that simplified assumptions and abstractions are usually made to simplify the problem when developing SRGMs. Selecting an appropriate SRGM should depend on the key characteristics of the software project. In this article, we propose a deep learning-based approach for software reliability prediction and assessment. Specifically, we clearly demonstrate how to derive mathematical expressions from the computational methods of deep learning models and how to determine the correlation between them and the mathematical formula of SRGMs, and then, we use the back-propagation algorithm to obtain the SRGM parameters. Furthermore, we further integrate some deep learning-based SRGMs and also propose a method for the weighted assignment of combinations. Three real open source software failure datasets are used to evaluate the performance of the proposed models compared to selected SRGMs. The experimental results reveal that our proposed deep learning-based models and their combinations perform better than several classical SRGMs.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to re...

Objectives Pulsed radiofrequency (PRF) stimulation is widely used for intractable pain; however, there is no consensus on treatment protocols and appropriate types of pain. We compared effectiveness of bipolar and unipolar PRF on neuropathic or inflammatory pains, and of targets at the dorsal root ganglion (DRG) and sciatic nerve (SN). We also examined efficacy of repetitive PRF stimulations. This preclinical study could serve as an extensive survey before human trials. Materials Spare nerve injury (SNI)-induced neuropathic pain and complete Freund's adjuvant (CFA) injection-induced inflammatory pain were used. Behavioral responses were measured using von Frey test, acetone test, and Hargreave's test at preinjury and postinjury time points. In both models, we evaluated results of DRG stimulation with unipolar PRF (45 V) versus bipolar PRF (5 V), stimulation at DRG vs. SN, and repetitive stimulations. Results Both unipolar and bipolar PRFs reduced SNI- or CFA-induced pain for a similar duration. In the SNI model, PRF-DRG had a stronger effect on tactile pain than PRF-SN but lower effect on cold allodynia, whereas in the CFA model PRF-DRG and PRF-SN showed similar effects. Repetitive PRF stimulation, by open technique or implantation method, produced analogous effect by each stimulus, and no evident analgesic tolerance or neurological deficit was shown. Conclusions PRF temporarily attenuates neuropathic and inflammatory pain. Bipolar PRF generates significant analgesia with a much lower electrical power than unipolar PRF. Meanwhile, the minor variant effects between PRF-DRG and PRF-SN may indicate distinct mechanisms. The sustained-analgesia by repetitive treatments suggests implantation technique could be a promising choice.

Objectives/hypothesis To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients. Study design Retrospective study. Methods Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups. Results The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate. Conclusions The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission. Level of evidence 4 Laryngoscope, 2021.

Objective To analyze the duration of gonadotropin hyperstimulation's impacts on oocyte quality and clinical outcomes in aged in vitro fertilization (IVF) patients. Materials and methods This retrospective study was carried out using IVF records of the Chang Gung Memorial Hospital IVF center from January 2017 to December 2019. A total of 308 IVF cycles with patients aged 40–44 years were included. Clinical characteristics of patients who received a short controlled ovarian hyperstimulation (COH) (i.e., 6–7 days; s-COH group) or a long COH treatment (i.e., 9–10 days; l-COH group) were compared. In addition, analysis was conducted using data within two age subgroups: 40–42 years and 42–44 years subgroups. Results The s-COH group received significantly lower total doses of gonadotropin and had smaller leading follicles at the time of ovulation trigger when compared to the l-COH group. The s-COH group also produced a significantly lower number of oocytes, mature metaphase II (MII) oocytes, and 2 PN zygotes compared to the l-COH group. However, there was no significant difference in the number of transferable and good-quality embryos between the two treatment groups. Likewise, the pregnancy rate and live birth rate were comparable in the s-COH and l-COH groups. Similar results were obtained when the analysis was limited to select age subgroups (i.e., 40–42 and 42–44 years subgroups). Conclusion While a long COH generates more oocytes per cycle, a 6–7 days COH treatment, which is at the lower end of the recommended window of stimulation, could achieve a pregnancy outcome comparable to that applied 9–10 days of COH in aged patients.

BACKGROUND Hepatic tuberculosis (TB) is uncommon clinically. Because of a lack of specific signs, characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain, hepatic TB is easily missed or misdiagnosed. CASE SUMMARY A 62-year-old Chinese man presented with jaundice for 1 wk and no abnormal laboratory tests other than elevated bilirubin, aminotransferases and C-reactive protein. Computed tomography (CT) of the abdomen showed a mass in the left lobe of the liver and hepatic hilum with striped calcified foci. Mild enhancement was visible at the edges, along with extensive intrahepatic biliary ductal dilatation in the right lobe of the liver. In the arterial phase of both CT and magnetic resonance imaging, the main trunk and right branch of the portal artery were partially visualized. Magnetic resonance cholangiopancreatography (MRCP) indicated that the left lobe of the liver and most of the bile ducts in the hilum were not visible. Pathological examination revealed coagulative necrosis, and granulomatous nodules were seen around areas of necrosis; therefore, TB was considered. CONCLUSION Hepatic tuberculosis is easily misdiagnosed or missed on imaging. Percutaneous puncture biopsy is the most useful tool for definitive diagnosis.

Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)‐induced sustained VT, and long duration of isoproterenol and tachypacing‐induced sustained and non‐sustained VT. Tachypacing‐induced sustained and non‐sustained VT in isoproterenol‐treated CKD RVOT tissues were attenuated by KB‐R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase‐positive neural density. The CKD RVOT myocytes exhibited large levels of I to, I Kr, NCX and L‐type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.

Mobile manipulators are increasingly applied to improve the efficiency in industrial manufacturing. As a typical system using multi-sensor fusion technology, accurate extrinsic calibration of manipulator’s exteroceptive sensors like camera and 2D-LiDAR is essential for mobile manipulators to perform complicated task such as mobile assembly. However, most existing camera-LiDAR calibration methods require sophisticated artificial calibration targets, leading to implementation restrictions. In this paper, by reconstructing an arbitrary trihedron that existed in the general human-made environment, a novel method is presented to estimate the transformation between the manipulator camera and the 2D-LiDAR coordinate system. The proposed method is based on the use of point, line, and plane geometry constraints between the segmented 2D-LiDAR scan and the reconstructed trihedron features. Considering the metric of reconstruction, the extended hand-eye calibration framework is implemented to recover the scale factor and hand-eye parameters. Then, a new optimization model is presented to reconstruct the key features of arbitrary trihedron in a preset global coordinate system. Finally, with only one 2D-LiDAR measurement, camera-LiDAR transformation can be calculated by constructing point-to-line and line-to-plane geometric constraints. Further, the transformation between the manipulator kinematic base and 2D-LiDAR can also be calibrated. Both simulation and real-world experiments show that the proposed method can provide robust and accurate results.

OBJECTIVE To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy. METHODS A multicenter prospective observational study was conducted to compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls). Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy were measured. RESULTS Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711-0.935]). A cutoff value of >0.25 ng/ml had a sensitivity of 87% and a specificity of 79%. CONCLUSION Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

Objective To assess whether lifelong higher circulating 25-hydroxyvitamin D [25(OH)D] levels increase serum calcium levels and kidney stone disease (KSD) risk. Methods Summary data for KSD were obtained from the UK biobank genome-wide association study (6536 cases and 388 508 controls). We acquired summary data for 25(OH)D from 120 618 Europeans and another large-scale analysis (443 734 Europeans) for primary and secondary analysis. Random-effect inverse-variance weighted (IVW) and 7 additional sensitivity analyses were applied. Next, multivariable Mendelian randomization (MVMR) was performed by introducing data for serum calcium levels. Results Genetic predisposition for a 1-SD higher 25(OH)D level was associated with increased serum calcium levels (IVW; beta, 0.014; 95% CI, 0.010-0.018; P = 7.64E-10). Genetically predicted higher circulating 25(OH)D levels were associated with increased the risk of KSD, with per 1-SD odds ratios (ORs) of 1.47 (95% CI, 1.22-1.77; P = 5.49E-05) and 1.36 (95% CI, 1.03-1.80; P = 0.029) using the IVW and MVMR-Egger methods, respectively. In secondary analysis, similar results were found: 25(OH)D was associated with an increased risk of KSD in univariate Mendelian randomization (IVW; OR 1.71; 95% CI, 1.26-2.32; P = 0.001) and MVMR (OR 1.43; 95% CI, 1.16-1.76; P < 0.001) analyses. Most sensitivity analyses were consistent with the primary results, both for the primary and secondary analyses. Conclusions Our study supports that higher genetically predicted lifelong circulating 25(OH)D levels are associated with higher calcium levels and KSD risk. The effects of 25(OH)D on KSD were partially attenuated—but still significant—in MVMR.

The treatment of emissions from natural gas engines is an important area of research since methane is a potent greenhouse gas. The benchmark catalysts, based on Pd, still face challenges such as water poisoning and long-term stability. Here we report an approach for catalyst synthesis that relies on the trapping of metal single atoms on the support surface, in thermally stable form, to modify the nature of further deposited metal/metal oxide. By anchoring Pt ions on a catalyst support we can tailor the morphology of the deposited phase. In particular, two-dimensional (2D) rafts of PdOx are formed, resulting in higher reaction rates and improved water tolerance during methane oxidation. The results show that modifying the support by trapping single atoms could provide an important addition to the toolkit of catalyst designers for controlling the nucleation and growth of metal and metal oxide clusters in heterogeneous catalysts. Despite its importance in the context of natural gas engines emissions treatment, methane oxidation remains challenging. Now, the authors introduce an approach to stabilize PdOx rafts on ceria by trapping Pt single atoms in the support resulting in a superior catalyst for this transformation.

Background The accuracy of estimating microvascular invasion (MVI) preoperatively in hepatocellular carcinoma (HCC) by clinical observers is low. Most recent studies constructed MVI predictive models utilizing radiological and/or radiomics features extracted from computed tomography (CT) images. These methods, however, rely heavily on human experiences and require manual tumor contouring. We developed a deep learning-based framework for preoperative MVI prediction by using CT images of arterial phase (AP) with simple tumor labeling and without the need of manual feature extraction. The model was further validated on CT images that were originally scanned at multiple different hospitals. Methods CT images of AP were acquired for 309 patients from China Medical University Hospital (CMUH). Images of 164 patients, who took their CT scanning at 54 different hospitals but were referred to CMUH, were also collected. Deep learning (ResNet-18) and machine learning (support vector machine) models were constructed with AP images and/or patients’ clinical factors (CFs), and their performance was compared systematically. All models were independently evaluated on two patient cohorts: validation set (within CMUH) and external set (other hospitals). Subsequently, explainability of the best model was visualized using gradient-weighted class activation map (Grad-CAM). Results The ResNet-18 model built with AP images and patients’ clinical factors was superior than other models achieving a highest AUC of 0.845. When evaluating on the external set, the model produced an AUC of 0.777, approaching its performance on the validation set. Model interpretation with Grad-CAM revealed that MVI relevant imaging features on CT images were captured and learned by the ResNet-18 model. Conclusions This framework provide evidence showing the generalizability and robustness of ResNet-18 in predicting MVI using CT images of AP scanned at multiple different hospitals. Attention heatmaps obtained from model explainability further confirmed that ResNet-18 focused on imaging features on CT overlapping with the conditions used by radiologists to estimate MVI clinically.

Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

We report on a simple approach of time-delayed reservoir computing (RC) based on a two-element phased laser array for image identification. Here the phased laser array with optical feedback and injection is trained according to the representative characteristics extracted through histograms of oriented gradients. These characteristic vectors are multiplied by a random mask signal to form input data, which are subsequently trained in the reservoir. By optimizing the parameters of the RC, we achieve an identification accuracy of 97.44% on the MNIST dataset and 85.46% on the Fashion-MNIST dataset. These results indicate that our proposed RC indeed allows accurate classification of handwritten digit and fashion production. Moreover, we further forecast an RC scheme based on a larger-scale phased laser array, which is expected to tackle more complex tasks at a high speed. Our work offers a possibility for advanced image processing using highly integrated neuromorphic photonic systems.

While bringing convenience to people, the growing number of vehicles on road already cause inevitable traffic congestion. Some traffic congestion happen with observable reasons, but others occur without apparent reasons or bottlenecks, which referred to as phantom jams, are caused by traditional vehicle following model. In order to alleviate the traffic instability caused by phantom jam, several models have been proposed with the development of intelligent transportation system (ITS). these have been proved to be able to suppress traffic instability in the ideal situation. But in road scenarios, uncertainties of vehicle state measurements and time delay caused by on-board sensors, inter-vehicle communications and control system of vehicles will affect the performance of the existing models severely, and cannot be ignored. In this paper, a novel predictable bilateral control model-PBCM, which consists of best estimation and state prediction is proposed to determine accurate acceleration values of the host vehicle in traffic flow to alleviate traffic instability. Theoretical analysis and simulation results show that our model could reduce the influence of the measurement errors and the delay caused by communication and control system effectively, control the state of the vehicles in traffic flow accurately, thus achieve the goal of restrain the instability of traffic flow., 13 pages, 35 figures

This study analyzed the effects of male age and abstinence time on semen quality and explored the best abstinence time for Chinese males among different age groups. Semen parameters, including sperm kinetics, morphology, and DNA fragmentation index (DFI), were reviewed from 2952 men. Samples were divided into six age groups (≤25 years, 26–30 years, 31–35 years, 36–40 years, 41–45 years, and >45 years) and were divided into six groups according to different abstinence time (2 days, 3 days, 4 days, 5 days, 6 days, and 7 days). The differences in semen quality between the groups were compared, and the effect of age and abstinence time on semen quality was analyzed. Significant differences were observed in semen volume, progressive motility (PR), and DFI among the age groups (all P < 0.05), and no significant differences were observed in sperm morphological parameters (all P > 0.05). There were significant differences in semen volume, PR, and DFI among different abstinence time groups (all P < 0.05) and no significant differences in sperm morphological parameters (all P > 0.05). Pearson analysis showed that male age and abstinence time were both significantly correlated with sperm kinetics and DFI (both P < 0.05), while no significant correlation was found with sperm morphological parameters (all P > 0.05). The box plots and histograms of men's age, abstinence time, and semen quality show that most semen quality parameters differ significantly between the 2 days and 7 days abstinence groups and other groups at different ages. Except for the sperm morphology parameters, sperm kinetic parameters and sperm DFI are linearly related to male age and abstinence time.

Two quantitative PCR (qPCR)–based methods, for clonal immunoglobulin or T-cell receptor gene (Ig/TCR) rearrangements and for fusion transcripts, are widely used for the measurement of minimal residual disease (MRD) in patients with B-precursor acute lymphoblastic leukemia (ALL). MRD of bone marrow samples from 165 patients carrying the three major fusion transcripts, including 74 BCR-ABL1, 54 ETV6-RUNX1, and 37 TCF3-PBX1, was analyzed by using the two qPCR-based methods. The correlation coefficient of both methods was good for TCF3-PBX1 (R2 = 0.8088) and BCR-ABL1 (R2 = 0.8094) ALL and moderate for ETV6-RUNX1 (R2 = 0.5972). The concordance was perfect for TCF3-PBX1 ALL (97.2%), substantially concordant for ETV6-RUNX1 ALL (87.1%), and only moderate for BCR-ABL1 ALL (70.6%). The discordant MRD, positive for only one method with a difference greater than one log, was found in 4 of 93 samples (4.3%) with ETV6-RUNX1, 31 of 245 samples (12.7%) with BCR-ABL1, and none of TCF3-PBX1 ALL. None of the eight non-transplanted patients with BCR-ABL1-MRD (+)/Ig/TCR-MRD (–) with a median follow-up time of 73.5 months had hematologic relapses. Our study showed an excellent MRD concordance between the two qPCR-based methods in TCF3-PBX1 ALL, whereas qPCR for Ig/TCR is more reliable in BCR-ABL1 ALL.

Our gut microbiome is constituted by trillions of microorganisms including bacteria, archaea and eukaryotic microbes. Nowadays, gut microbiome has been gradually recognized as a new organ system that systemically and biochemically interact with the host. Accumulating evidence suggests that the imbalanced gut microbiome contributes to the dysregulation of immune system and the disruption of cardiovascular homeostasis. Specific microbiome profiles and altered intestinal permeability are often observed in the pathophysiology of cardiovascular diseases. Gut-derived metabolites, toxins, peptides and immune cell-derived cytokines play pivotal roles in the induction of inflammation and the pathogenesis of dysfunction of heart and vasculature. Impaired crosstalk between gut microbiome and multiple organ systems, such as gut-vascular, heart-gut, gut-liver and brain-gut axes, are associated with higher cardiovascular risks. Medications and strategies that restore healthy gut microbiome might therefore represent novel therapeutic options to lower the incidence of cardiovascular and metabolic disorders.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson’s correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = −0.69, p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.

Introduction Androgen deprivation therapy (ADT) is a key treatment modality in the management of prostate cancer (PCa), especially for patients with metastatic disease. Increasing evidences suggest that patients who received ADT have increased incidence of diabetes, myocardial infarction, stroke, and even mortality. It is important to understand the pathophysiological mechanisms on how ADT increases cardiovascular risk and induces cardiovascular events, which would provide important information for potential implementation of preventive measures. Methods Twenty-six 12-week-old male SD rats were divided into four groups for different types of ADTs including: the bilateral orchidectomy group (Orx), LHRH agonist group (leuprolide), LHRH antagonist group (degarelix), and control group. After treated with drug or adjuvant injection every 3 weeks for 24 weeks, all rats were sacrificed and total blood were collected. Aorta, renal arteries, and kidney were preserved for functional assay, immunohistochemistry, western blot, and quantitative reverse-transcription polymerase chain reaction. Results In vascular reactivity assays, aorta, intrarenal, and coronary arteries of all three ADT groups showed endothelial dysfunction. AT1R and related molecules at protein and messenger RNA (mRNA) level were tested, and AT1R pathway was shown to be activated and played a role in endothelial dysfunction. Both ACE and AT1R mRNA levels were doubled in the aorta in the leuprolide group while Orx and degarelix groups showed upregulation of AT1R in the kidney tissues. By immunohistochemistry, our result showed higher expression of AT1R in the intrarenal arteries of leuprolide and degarelix groups. The role of reactive oxygen species in endothelial dysfunction was confirmed by DHE fluorescence, nitrotyrosine overexpression, and upregulation of NOX2 in the different ADT treatment groups. Conclusion ADT causes endothelial dysfunction in male rats. GnRH receptor agonist compared to GnRH receptor antagonist, showed more impairment of endothelial function in the aorta and intrarenal arteries. Such change might be associated with upregulation and activation of AngII-AT1R-NOX2 induced oxidative stress in the vasculature. These results help to explain the different cardiovascular risks and outcomes related to different modalities of ADT treatment.

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. The male gender (OR = 2.02, 95% CI 1.46–2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13–2.38), multifocality (OR = 1.87, 95% CI 1.40–2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64–5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40–0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42–0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

The development of pressure sensor arrays capable of distinguishing the shape and texture details of objects is of considerable interest in the emerging fields of smart robots, prostheses, human-machine interfaces, and artificial intelligence (AI). Here we report an integrated pressure sensor array, by combining solution-processed two-dimensional (2D) MoS2 van der Waals (vdW) thin film transistor (TFT) active matrix and conductive micropyramidal pressure-sensitive rubber (PSR) electrodes made of polydimethylsiloxane/carbon nanotube composites, to achieve spatially revolved pressure mapping with excellent contrast and low power consumption. We demonstrate a 10 × 10 active matrix by using the 2D MoS2 vdW-TFTs with high on-off ratio > 106, minimal hysteresis, and excellent device-to-device uniformity. The combination of the vdW-TFT active matrix with the highly uniform micropyramidal PSR electrodes creates an integrated pressure sensing array for spatially resolved pressure mapping. This study demonstrates that the solution-processed 2D vdW-TFTs offer a solution for active-matrix control of pressure sensor arrays, and could be extended for other active-matrix arrays of electronic or optoelectronic devices.

It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Neighborhood socioeconomic deprivation is associated with adverse outcomes after pediatric liver transplant. We sought to determine if this relationship varies by transplant center. Using SRTR, we included patients

Whether selective serotonin reuptake inhibitors (SSRIs) can improve cognitive function in depressed patients remains unclear. We aimed to explore the effect of SSRIs on cognitive function and the influencing factors in patients with major depressive disorder (MDD) with impaired cognitive function. We used a neurocognitive test battery to assess five cognitive domains, namely, attention/vigilance, learning, memory, processing speed and executive functioning, and calculated the Global Deficit Score (GDS). A GDS≥0.5 indicated overall cognitive impairment. The changes in the cognitive domains and overall cognitive function were analyzed in MDD patients with a baseline GDS≥0.5 who completed 8 weeks of SSRI treatment. We divided the patients into the cognitive remission and nonremission groups to explore the associated factors. In total, 160 patients (mean age 37.6 ± 10.8 years, 30.6% male) were included in the final analysis. The median (quartiles) of baseline GDS and HRSD17 were 1.4 (0.8, 1.9) and 19.5 (17.0, 23.0), respectively. All five cognitive domains improved after the treatment, while only 41 (25.6%) patients achieved cognitive remission. Recurrence and a higher baseline GDS were risk factors for cognitive nonremission. More aggressive interventions may be needed to promote cognitive remission in clinical practice, especially for patients with severe cognitive impairment and recurrent episodes.

Background Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes. Objective To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs. Design Prospective cohort. (ClinicalTrials.gov: NCT02411396). Setting 4 U.S. sites, with recruitment between April 2015 and December 2016. Participants Adults with SCD living within 60 miles of a study site. Measurements Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment. Results Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED. Limitation The study was restricted to participants with uncomplicated VOCs. Conclusion In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED. Primary funding source Patient-Centered Outcomes Research Institute.

BACKGROUND A pediatric brain tumor requires multimodal therapy that can have serious effects on the ill child that can involve shared decision-making (SDM). Understanding this experience of SDM from the parents' point of view is understudied. OBJECTIVE The aim of this study was to explore the nature of lived experiences of parents during the SDM process when their child is being treated for a brain tumor. METHODS This was a descriptive phenomenology study using in-depth interviews with parents who had a child with a brain tumor. RESULTS Six major themes emerged: (1) early confusion associated with medical decision-making, (2) determining treatment via decision-making, (3) faith strengthening the direction of decision-making, (4) constructing consensus based on partnership, (5) adjusting lifestyle to coexist with the illness, and (6) positive energy and abundant support are able to open a window to the soul. CONCLUSION Shared decision-making is a process, and the experiences start with parental confusion about medical treatment. The process involves building a trusting relationship with health professionals that includes sharing medical treatment information and is eventually associated with normalizing the life of both the child and the rest of the family. IMPLICATIONS FOR PRACTICE Trusting relationships and partnership are vital for SDM to be successful. It is essential during the SDM process to strengthen parental resilience by supplying sufficient information and to support parental efforts to normalize their family life.

To investigate the role of the lncRNA growth arrest special 5 (GAS5) in ovarian clear cell carcinoma (OCCC), we measured the expression of GAS5 and miR‐31‐5p in OCCC tissue samples and OCCC cell lines using RT‐qPCR. MTT and colony formation assays were used to measure cell viability and colony formation ability. Cell invasion was determined by Transwell assays. The binding between GAS5 and miR‐31‐5p as well as miR‐31‐5p and ARID1A was determined by dual‐luciferase reporter assays. The ARID1A protein levels were detected using western blotting. Kaplan–Meier curves were used for the analysis of the 5‐year survival rate of patients with OCCC. GAS5 and ARID1A levels were significantly decreased, while miR‐31‐5p levels were strongly elevated in the OCCC tissues and cell lines. Patients with lower GAS5/ARID1A levels had shorter overall survival times. Overexpression of GAS5 or inhibition of miR‐31‐5p suppressed cell viability and invasion of OCCC cells and upregulated the protein levels of ARID1A. Moreover, overexpression of miR‐31‐5p reversed the effects of overexpression of GAS5. Cotransfection with pcDNA3.1‐GAS5 and miR‐31‐5p inhibitor led to the lowest cell viability and cell invasion rates. A dual‐luciferase reporter assay was performed to confirm the target relationship between GAS5 and miR‐31‐5p, as well as between miR‐31‐5p and ARID1A. LncRNA GAS5 inhibited cell viability and invasion of OCCC through activation of ARID1A by sponging miR‐31‐5p.

A low profile ultra-wideband tightly coupled dipole array is studied. The antenna elements are fed by Marchand baluns of small size and low cost. A metasurface based wide-angle impedance matching (MSWAIM) layer is introduced to replace the traditional dielectric WAIM, improving the beam scan performance and reducing the antenna profile. The simulation shows that the proposed antenna array can operate over 2.4-12.4 GHz, approximately 5:1 bandwidth with maximum scanning angle of 50o for both E plane and 45o for H plane. The antenna profile above the ground is only 0.578λH at the highest operating frequency. This antenna array can find its application in the forthcoming massive MIMO beamforming systems for 5G.

Flexible piezoelectric thin films are raising interest in energy harvesting and wearable electronics, although their direct fabrication is challenging in the selection of substrates and thermal processing. In this work, we developed direct fabrication of flexible lead-free (K, Na)NbO3 (KNN)-based piezoelectric films on commercially available metallic foils by sol-gel processing. Stainless steel and platinum foils are selected as flexible substrates because of their good thermal stability, robust flexibility, and cost-efficiency. The sol-gel-processed KNN-based thin films on both of the metallic foils show good flexibility, with the bending radii reaching ±3 mm. The flexible thin films grown on stainless steel and platinum foils present high breakdown electric fields that reach 1760 and 2530 kV/cm, respectively, resulting from the fine-grained dense structure, limited leakage current density, and suppressed mobility of charged carriers. Improved effective piezoelectric coefficient d33, eff* (75.4 pm/V) with a slight decrease after bending was obtained in the flexible thin films on Pt when compared to their rigid counterparts. The flexible lead-free piezoelectric thin films with combined high breakdown electric fields and piezoelectric and energy storage properties may pave the way for integrating KNN-based multifunctional thin films into flexible electronics.