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OBJECTIVES: The polymer polyetheretherketone (PEEK) is gradually being used in dental restorations because of its excellent mechanical properties, chemical resistance, fatigue resistance, thermal stability, radiation translucency and good biocompatibility. To process PEEK dentures with lower surface roughness as quickly as possible, the non-dominated sorting genetic algorithm-II (NSGA-II) integrated genetic algorithm back propagation (GABP) neural network was proposed, which can adjust the combination of process parameters for milling PEEK dentures. METHODS: The PEEK machining was conducted using a four-axis dental milling machine at different process parameters. The surface roughness of PEEK dentures was characterized using surface roughness profiler and scanning electron microscopy (SEM). The optimum machining performance of milling PEEK dentures was investigated using a multi-objective optimization model named as NSGA-II integrated GABP neural network algorithm. The surface roughness (Ra) and material removal rate (MRR) were used as optimization objectives. RESULTS: The multi-objective optimization model effectively improved surface roughness and machining efficiency for milling PEEK dentures. The validation experiments showed that the surface roughness of all PEEK dentures was less than 0.2µm, which was within the range of surface roughness set in this paper. The GABP surface roughness prediction model had an average error of 6 %. For the same surface roughness value, the optimized milling parameters all had a greater material removal rate. SIGNIFICANCE: The research results can improve current PEEK denture CAD/CAM technology by providing appropriate milling parameters using NSGA-II integrated GABP algorithm.
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Direct 3D printing of liquid metal is difficult to form and easy to destroy. In this paper, we developed a 3D printed composite material consisting of a thermoplastic polyurethane (TPU) matrix and liquid metal (LM) dispersed droplets, and introduced the method for realizing 3D printed devices with this composite material: First, the LM is added to 10~50wt %TPU at 190~200 °C through ultrasonic blending to prepare blended ink. After solid cooling, the LM-TPU composite fiber with a diameter of 600â µm was prepared by Wellzoom desktop extruder at 190 °C at an extrusion speed of 400â mm/min. It has excellent elasticity, with a tensile limit of 0.637â N/m2, and the TPU could evenly wrap LM droplets. Finally, the LM-TPU fiber is 3D printed at 240 °C by using a 3D printer, and 2D/3D flexible electronic devices with heating and conductive functions could be prepared. The microcircuit has good electrical conductivity; after adding voltage, the circuit has heat release; it could be used as heating equipment to keep warm and used in various flexible wearable electronic products.
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An electrochemical aptasensor for detecting lipopolysaccharides (LPS) was fabricated based on DNA-templated copper nanoparticles (DNA-CuNPs) and RecJf exonuclease-assisted target recycling. The DNA-CuNPs were synthesized on a double-stranded DNA template generated through the hybridization of the LPS aptamer and its complementary chain (cDNA). In the absence of LPS, the CuNPs were synthesized on DNA double-strands, and a strong readout corresponding to the CuNPs was achieved at 0.10 V (vs. SCE). In the presence of LPS, the fabricated aptamer could detach from the DNA double-strand to form a complex with LPS, disrupting the template for the synthesis of CuNPs on the electrode. Meanwhile, RecJf exonuclease could hydrolyze the cDNA together with this single-stranded aptamer, releasing the LPS for the next round of aptamer binding, thereby enabling target recycling amplification. As a result, the electrochemical signal decreased and could be used to indicate the LPS content. The fabricated electrochemical aptasensor exhibited an extensive dynamic working range of 0.01 pg mL-1 to 100 ng mL-1, and its detection limit was 6.8 fg mL-1. The aptasensor also exhibited high selectivity and excellent reproducibility. Moreover, the proposed aptasensor could be used in practical applications for the detection of LPS in human serum samples.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Humanos , Exonucleasas/química , Exonucleasas/metabolismo , Lipopolisacáridos , Cobre/química , ADN Complementario , Reproducibilidad de los Resultados , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Técnicas Electroquímicas , ADN/química , Nanopartículas del Metal/químicaRESUMEN
The phenolic compound trichlorophenol (TCP) is an ingredient in fungicides and herbicides. This compound's high stability, bioaccumulation, toxicity, and poor biodegradability result in severe environmental and biological health issues. Consequently, it is crucial to have an affordable and sensitive method for detecting TCP in environmental samples. In this study, α-phase bismuth oxide microplates and polydopamine-functionalized reduced graphene oxide (α-Bi2O3 MPs/PDA-RGO) were synthesized using a simple ultrasonic method and characterized with various analytical and physical characterizations. The conversion of the catechol moieties present in the resulting PDA-RGO material into quinones facilitates productive interactions with diverse functional groups, such as hydroxyl, amine, and imine. Consequently, the compounds 2,4,6-trichlorophenol (TCP) engages in electrochemical interactions with the aforementioned functional groups. As a result, TCP shows more excellent selectivity on the designed α-Bi2O3 MPs/PDA-RGO/SPCE sensor. Under the optimized conditions, the sensor demonstrated a lower detection limit (0.0042 µM), a limit of quantification (0.0078 µM), good sensitivity (2.24 µA µM-1 cm2), a wide linear range (0.019-190.7 and 212.7-1649 µM), and pinpoint specificity. The efficacy of the sensor is additionally validated through the accurate identification of TCP residues in water, soil, and food samples.
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Grafito , Grafito/química , Fenoles , Agua , Técnicas Electroquímicas/métodosRESUMEN
A mild late-stage modification of pyrrolo[2,1-a]isoquinolines was established through iron-catalyzed oxidative dearomatization and peroxidation. Peroxylated pyrroloisoquinolines have been prepared readily with hydroperoxide in low to good yields (up to 72%) at room temperature. Interestingly, the treatment of fully aromatized pyrrolo[1,2-a]quinolines under the current reaction system resulted in the formation of ring-opening products.
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This paper focuses on the latest research printing technology and broad application for flexible liquid metal (LM) materials. Through the newest template printing method, centrifugal force assisted method, pen lithography technology, and laser method, the precision of liquid metal printing on the devices was improved to 10 nm. The development of novel liquid metal inks, such as PVA-LM ink and ethanol/PDMS/LM double emulsion ink, have further enhanced the recovery, rapid printing, high conductivity, and strain resistance. At the same time, liquid metals also show promise in the application of biochemical sensors, photocatalysts, composite materials, driving machines, and electrode materials. Liquid metals have been applied to biomedical, pressure/gas, and electrochemical sensors. The sensitivity, biostability, and electrochemical performance of these LM sensors were improved rapidly. They could continue to be used in healthy respiratory, heartbeat monitoring, and dopamine detection. Meanwhile, the applications of liquid metal droplets in catalytic-assisted MoS2 deposition, catalytic growth of two-dimensional (2D) lamellar, catalytic free radical polymerization, catalytic hydrogen absorption/dehydrogenation, photo/electrocatalysis, and other fields were also summarized. Through improving liquid metal composites, magnetic, thermal, electrical, and tensile enhancement alloys, and shape memory alloys with excellent properties could also be prepared. Finally, the applications of liquid metal in micro-motors, intelligent robot feet, nanorobots, self-actuation, and electrode materials were also summarized. This paper comprehensively summarizes the practical application of liquid metals in different fields, which helps understand LMs development trends, and lays a foundation for subsequent research.
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BACKGROUND: Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area. METHODS: We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People's Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment. RESULTS: Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p' = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover. CONCLUSION: There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.
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Disfunción Cognitiva , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Amígdala del Cerebelo/diagnóstico por imagen , Cognición , Encéfalo , Disfunción Cognitiva/diagnóstico por imagenRESUMEN
OBJECTIVES: This study aims to characterise the physical and psychological well-being of maternal and newborn healthcare workers (MNHCWs) during the COVID-19 pandemic. DESIGN: Observational repeated cross-sectional study. SETTING: An online questionnaire was distributed to MNHCWs around the globe in three separate rounds from March 2020 to March 2021. PARTICIPANTS: Total samples of N=1357 (round 1) and N=420 (round 3) primarily consisted of doctors, midwives and nurses in maternal and newborn specialties. Samples represented all WHO regions, with 33% (round 1) and 42% (round 3) from low- or middle-income countries (LMICs). PRIMARY AND SECONDARY OUTCOME MEASURES: Responses from rounds 1 (March-June 2020) and 3 (December 2020-March 2021) were analysed to measure self-reported levels of relative stress and workplace protection from COVID-19, while associated factors were determined through multivariable ordinal logistic regression. RESULTS: In round 1, 90% of MNHCWs reported increased stress levels and 45% reported insufficient personal protective equipment (PPE) access. Nurses and physicians were less likely to report increased stress than midwives at the pandemic onset. Factors associated with increased stress included being female, being from an LMIC and insufficient PPE. In round 3, 75% reported similar or increased stress while 10% reported insufficient PPE. In both rounds, over 50% of MNHCWs felt relatively or completely unprotected from COVID-19 in the workplace. Those from LMICs were more likely to report feeling unprotected, while receiving organisational information that valued safety was associated with better feelings of protection in the workplace. CONCLUSIONS: Among our international sample of MNHCWs, we observed high rates of self-reported stress increase at the start of the pandemic with persistence or increase up to a year later. High rates of feeling unprotected persisted even as PPE became more available. These results may inform interventions needed to support and protect MNHCWs during this and future pandemics.
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COVID-19 , Médicos , Recién Nacido , Humanos , Femenino , Masculino , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , Pandemias , AutoinformeRESUMEN
The prestressed and steel-reinforced concrete slab (PSRCS) is an innovative composite structural member offering high load capacity and stiffness and exceptional anti-crack performance, making it a leading trend in composite structures. This paper presents the derived calculation formulas for bearing capacity, section stiffness, mid-span deflection of PSRCS. Additionally, a numerical analysis of PSRCS is conducted using ABAQUS software, with several models created to systematically investigate bearing capacity, section stiffness, anti-crack performance, and failure mode. Concurrently, PSRCS member parameters are analyzed for optimal design, and the results of finite element (FE) calculations are compared with theoretical formula calculations. The results demonstrate that PSRCS exhibits superior load capacity, section stiffness, and anti-crack performance comparing to conventional slabs. The parametric analysis offers optimal design for each parameter and presents the corresponding recommended span-to-depth ratios for various spans in PSRCS applications.
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Purpose: Maintaining adherence to antipsychotic (AP) medication is often challenging. Aripiprazole tablets with sensor (AS) contain an ingestible event marker and communicate with wearable patches and a smartphone app to provide objective medication ingestion data. This study evaluated real-world treatment patterns of AS usage and its impact on psychiatric healthcare resource utilization (HCRU). Patients and Methods: This retrospective, observational cohort study identified individuals who initiated AS between 1/1/2019 and 6/30/2020 with 3 months baseline and 6 months of follow-up data using a commercial medical and pharmacy claims database (Clarivate). Controls were propensity score-matched (4:1) to AS initiators based on age (±2 years), sex, diagnosis (major depressive disorder [MDD], schizophrenia, bipolar I disorder [BP-I], other), insurance, and baseline oral AP use (yes/no). Days of AP supply were evaluated using a general regression model. The frequency of psychiatric HCRU during follow-up was compared between groups using a zero-inflated regression model. Results: Most AS initiators were diagnosed with MDD (61.2%) and were women (61.2%); mean age was 37.7 years (standard deviation: 14.1). Most AS initiators (53.1%) continued treatment for >60 days (mean days of supply = 77). After adjusting for covariates, AS initiators had 41% more days of AP supply during follow-up compared with controls (P <0.0001) and significantly lower adjusted odds ratios (ORs) for psychiatric outpatient visits (adjusted OR = 0.80; P <0.05), emergency department visits (adjusted OR = 0.11; P <0.05), inpatient visits (adjusted OR = 0.42; P <0.05), and other medical services (adjusted OR = 0.25; P <0.05). Conclusion: Participants who implemented AS had significantly more days of AP supply and fewer psychiatric care visits. These preliminary results suggest AS usage can help build regular medication-taking habits and holds promise for reducing psychiatric HCRU. Additional studies with larger sample sizes are warranted to inform clinical practice and coverage decisions.
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AIM: To investigate changes of choroidal thickness (ChT) in children with myopia and the effect of current myopia control interventions on ChT. METHODS: Major literature databases were searched for studies relevant to myopia in children. All studies used swept-source optical coherence tomography (SS-OCT) or enhanced depth imaging optical coherence tomography (EDI-OCT) to measure the ChT value. The weighted mean difference (WMD) and 95% confidence interval (CI) were pooled to evaluate ChT in myopia children. RESULTS: A total of 11 eligible articles, including 1693 myopic and 1132 non-myopic eyes, were included in the first Meta-analysis. The sub-foveal choroidal thickness (SFCT; WMD=-40.06, 95%CI, -59.36 to -20.75, P<0.001) and ChT at other sectors were significantly thinner in myopic eyes compared with the non-myopic eyes. The Meta-analysis revealed that the ChT decreased horizontally from the temporal sector toward the nasal sector in the pediatric myopia population. Another 11 studies reporting the effect of myopia control interventions were included in the second Meta-analysis for the relationship between myopia control treatments and ChT. SFCT significantly increased after orthokeratology (OK) treatment and OK combined with 0.01% atropine (OKA) treatment (WMD=19.47, 95%CI, 15.96 to 22.98, P<0.001; WMD=21.81, 95%CI, 12.92 to 29.70, P<0.001, respectively). The forest plots showed that SFCT changed little in myopic children receiving 0.01% atropine (P=0.30). Furthermore, the Meta-analysis showed that OK treatment had a stronger effect on the value of SFCT in myopic children as compared with 0.01% atropine (WMD=9.86; 95%CI, -0.21 to 19.93, P=0.05). There is no difference between the treatment with OK and OKA treatment in ChT in myopic children (P=0.37). CONCLUSION: The ChT in myopic eyes is thinner than that in non-myopic eyes in pediatric population. Myopia control interventions including OK and OKA lead to ChT thickening, but other treatments such as 0.01% atropine did not show an increase in ChT.
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pH is one of the important parameters of a biological microenvironment, which is closely related to cell growth, development, vitality, division, and differentiation. Monitoring the pH of a microenvironment is helpful to monitor the cell metabolism as well as to understand the cellular life cycle. The sensitivity of liquid metals (LMs) to hydrogen ions has aroused our interest. Here, we propose a novel but facile pH sensor using liquid gallium (LM for short) droplet morphological change as the readout. The pH sensing characteristics of the LM droplet were examined, especially the shape response. LM can form solid native oxide skin rapidly in oxygenated solution, and the oxide layer will be removed in acidic or alkaline solutions, which will cause a great change in surface tension. The phenomenon is the change of LM morphology from macroscopic observation. We explored the electrochemical characteristics of LM at different pH values, explained the mechanism of surface change, and calibrated the relationship curve between LM morphology and pH and the interference of impurity ions on the sensor. Finally, we proposed a detection algorithm for the LM pH morphology sensor and tried to automatically detect pH with a mobile app, which was applied to the pH detection of cell culture solution. We believe that the response characteristics of LM to hydrogen ions have great potential in microenvironment detection.
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Galio , Protones , Iones , Concentración de Iones de Hidrógeno , ÓxidosRESUMEN
In this work, iron-based metal organic frameworks (Fe-MOF) are used as a self-sacrifice beacon to produce Prussian blue (PB). Then, a dual-mode electrochemical-colorimetric biosensing platform for kanamycin (KAN) detection is established considering the prominent redox activity and blue color of PB. CoFe2O4 magnetic nanobeads (CoFe2O4 MBs) are employed for immobilization and separation of the signal beacon in the complex matrix, and the combination between CoFe2O4 MBs and magnetic electrodes simplifies the electrochemical testing process. The linear range of the electrochemical mode is 0.1 nM-1.0 µM with a detection limit of 39 pM, and that of the colorimetric mode is 10 nM-2.0 µM with a detection limit of 3.6 nM. Furthermore, the dual-mode strategy shows satisfactory specificity and enhanced applicability for KAN detection in real samples. Compared with known dual-mode determination methods, the proposed design employs the same reaction to produce two signal output modes, thus eliminating the effect of different reactive pathways on the outcome and in turn promoting greater accuracy.
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Técnicas Biosensibles , Colorimetría , Kanamicina , Técnicas Electroquímicas/métodos , Oro , Técnicas Biosensibles/métodos , Fenómenos MagnéticosRESUMEN
To clarify the regulatory effect and molecular mechanism of Arisaema heterophyllum Blume (AhBl) monomer stigmasterol on lung adenocarcinoma in human lung adenocarcinoma cells NCI-H1975 cultured in vitro and in nude mice. Oil red O staining, free fatty acid detection, adenosine triphosphate (ATP), and NADPH were applied to elucidate the regulatory effect of stigmasterol on the energy metabolism of NCI-H1975 cells. Simultaneously, colony formation assay and nude mouse tumorigenesis were performed to clarify the underlying mechanisms of stigmasterol on the proliferation and tumorigenesis of NCI-H1975 cells. Furthermore, peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 was supplemented to determine the expression changes of cyclins to clarify the regulation mechanism of stigmasterol. The results revealed that stigmasterol administration markedly inhibited the viability but promoted lipid deposition of NCI-H1975 cells. Meanwhile, the reduction of cell energy metabolism affected cell proliferation and colony formation. qPCR and western blot assays indicated that stigmasterol played a role in regulating the expression of cyclins and PPARγ signaling pathway proteins. Nude mouse tumorigenesis suggested that tumor size and weight in the stigmasterol-treated group were apparently lower as compared with the control group. Tumor tissue cells developed varying degrees of degeneration and large areas of ischemic necrosis presented in the central and peripheral cells. Immunohistochemistry results revealed that Ki67 expression in the stigmasterol group was substantially inhibited, while PPARγ expression was greatly elevated as compared with the control. GW9662 could mediate the inhibitory effect of stigmasterol on NCI-H1975 cells. The current study demonstrated that stigmasterol targeted PPARγ and inhibited the viability and tumorigenicity of lung adenocarcinoma cells NCI-H1975.
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High-performance and intelligent fibers are indispensable parts of wearable electronics in the future. This work mainly demonstrates the preparation of flexible intelligent liquid metal (LM) fibers with three core-sheath structures. An ultra-thin (10-50 µm), conductive, and highly flexible LM was deposited on the fiber core [carbon/polyethylene terephthalate (C/PET)--150-500 µm] along the fiber direction and then deposited on a polymer-protective layer [polyvinyl alcohol/epoxy resin (PVA/EP)--10 µm]. Four kinds of LM intelligent fibers were manufactured, including the C-LM-PVA fiber, C-LM-EP fiber, PET-LM-PVA fiber, and PET-LM-EP fiber. These LM intelligent fibers (diameter, 150-600 µm) were demonstrated with a high conductivity of 7.839 × 104 S·m-1. The changes in resistance in different torsion directions were measured, and these smart LM fibers could also be used as electrical heaters or thermoelectric generators, which released heat (36-36.9 °C/1-1.5 V) into the environment. Then, these multifunctional LM fibers were applied as high-performance strain sensors and bending sensors. These flexible LM conductive fibers could be successfully utilized in intelligent wearable fabrics and were expected to be widely utilized in artificial muscle and sensor fields.
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BACKGROUND: To investigate the mortality and health care resource use among patients with severe or critical coronavirus disease of 2019 (COVID-19) in the first wave of pandemic in China. METHODS: We performed a systematic review and meta-analysis to investigate the mortality, discharge rate, length of hospital stay, and use of invasive ventilation in severe or critical COVID-19 cases in China. We searched electronic databases for studies from China with no restrictions on language or interventions patients received. We screened records, extracted data and assessed the quality of included studies in duplicate. We performed the meta-analysis using random-effect models through a Bayesian framework. Subgroup analyses were conducted to examine studies by disease severity, study location and patient enrolment start date. We also performed sensitivity analysis using various priors, and assessed between-study heterogeneity and publication bias for the primary outcomes. RESULTS: Out of 6,205 titles and abstracts screened, 500 were reviewed in full text. A total of 42 studies were included in the review, of which 95% were observational studies (n = 40). The pooled 28-day and 14-day mortalities among severe or critical patients were 20.48% (7,136 patients, 95% credible interval (CrI), 13.11 to 30.70) and 10.83% (95% CrI, 6.78 to 16.75), respectively. The mortality declined over time and was higher in patients with critical disease than severe cases (1,235 patients, 45.73%, 95% CrI, 22.79 to 73.52 vs. 3,969 patients, 14.90%, 95% CrI, 4.70 to 39.57) and patients in Hubei compared to those outside Hubei (6,719 patients, 26.62%, 95% CrI, 13.11 to 30.70 vs. 244 patients, 5.88%, 95% CrI 2.03 to 14.11). The length of hospital stay was estimated at 18.48 days (6,847 patients, 95% CrI, 17.59 to 21.21), the 28-day discharge rate was 50.48% (3,645 patients, 95% CrI, 26.47 to 79.53), and the use of invasive ventilation rate was 13.46% (4,108 patients, 95% CrI, 7.61 to 22.31). CONCLUSIONS: Our systematic review and meta-analysis found high mortality among severe and critical COVID-19 cases. Severe or critical COVID-19 cases consumed a large amount of hospital resources during the outbreak.
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COVID-19 , Cuidados Críticos , Tiempo de Internación , Pandemias , SARS-CoV-2 , COVID-19/mortalidad , COVID-19/terapia , China/epidemiología , Enfermedad Crítica , Humanos , Índice de Severidad de la EnfermedadRESUMEN
Conventional patterning methods for producing liquid metal (LM) electronic circuits, such as the template method, use chemical etching, which requires long cycle times, high costs, and multiple-step operations. In this study, a novel and reliable laser engraving micro-fabrication technology was introduced, which was used to fabricate personalized patterns of LM electronic circuits. First, by digitizing the pattern, a laser printing technology was used to burn a polyethylene (PE) film, where a polydimethylsiloxane (PDMS) or paper substrate was used to produce grooves. Then, the grooves were filled with LM and the PE film was removed; finally, the metal was packaged with PDMS film. The experimental results showed that the prepared LM could fabricate precise patterned electronic circuits, such as golden serpentine curves and Peano curves. The minimum width and height of the LM circuit were 253 µm and 200 µm, respectively, whereas the printed LM circuit on paper reached a minimum height of 26 µm. This LM flexible circuit could also be adapted to various sensor devices and was successfully applied to heart rate detection. Laser engraving micro-processing technologies could be used to customize various high-resolution LM circuit patterns in a short time, and have broad prospects in the manufacture of flexible electronic equipment.
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BACKGROUND: The objective of this study was to characterize hospitalized coronavirus disease 2019 (COVID-19) patients and describe their real-world treatment patterns and outcomes over time. METHODS: Adult patients hospitalized on May 1, 2020-December 31, 2020 with a discharge diagnosis of COVID-19 were identified from the Premier Healthcare Database. Patient and hospital characteristics, treatments, baseline severity based on oxygen support, length of stay (LOS), intensive care unit (ICU) utilization, and mortality were examined. RESULTS: The study included 295657 patients (847 hospitals), with median age of 66 (interquartile range, 54-77) years. Among each set of demographic comparators, the majority were male, white, and over 65. Approximately 85% had no supplemental oxygen charges (NSOc) or low-flow oxygen (LFO) at baseline, whereas 75% received no more than NSOc or LFO as maximal oxygen support at any time during hospitalization. Remdesivir (RDV) and corticosteroid treatment utilization increased over time. By December, 50% were receiving RDV and 80% were receiving corticosteroids. A higher proportion initiated COVID-19 treatments within 2 days of hospitalization in December versus May (RDV, 87% vs 40%; corticosteroids, 93% vs 62%; convalescent plasma, 68% vs 26%). There was a shift toward initiating RDV in patients on NSOc or LFO (68.0% [May] vs 83.1% [December]). Median LOS decreased over time. Overall mortality was 13.5% and it was highest for severe patients (invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO], 53.7%; high-flow oxygen/noninvasive ventilation [HFO/NIV], 32.2%; LFO, 11.7%; NSOc, 7.3%). The ICU use decreased, whereas mortality decreased for NSOc and LFO. CONCLUSIONS: Clinical management of COVID-19 is rapidly evolving. This large observational study found that use of evidence-based treatments increased from May to December 2020, whereas improvement in outcomes occurred over this time-period.
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BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.