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The adoption of neoadjuvant concurrent chemoradiotherapy (CCRT) has reshaped the therapeutic landscape, but response prediction remains challenging. This study investigates the interaction between pre-CCRT carcinoembryonic antigen (CEA) and post-CCRT hemoglobin (Hb) levels in predicting the response of locally advanced rectal cancer (LARC) to CCRT. Retrospective data from 93 rectal cancer patients receiving neoadjuvant CCRT were analyzed. Univariate analyses assessed clinical factors associated with tumor regression grade (TRG) and T-stage outcomes. Machine learning identified predictive biomarkers. Interaction effects between CEA and Hb were explored through subgroup analyses. Post-CCRT Hb varied between pre-CCRT CEA groups. The interaction between pre-CCRT CEA and post-CCRT Hb influenced TRG. Males with normal pre-CCRT CEA and anemia showed better treatment responses. Females with elevated pre-CCRT CEA and post-CCRT anemia exhibited poorer responses. The interaction effect between them was significant, indicating that their relationship with TRG was not additive. Inflammatory biomarkers, WBC, neutrophil count, and post-CCRT platelet level correlated with CCRT response. Contrasting with previous findings, anemia was a predictor of better treatment response in males with normal pre-CCRT CEA. The interaction between pre-CCRT CEA and post-CCRT Hb levels predicts the response of LARC to CCRT. CEA, Hb, and sex should be considered when assessing treatment response. Inflammatory biomarkers contribute to response prediction. Understanding these complex relationships can enhance personalized treatment approaches in rectal cancer patients.
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Urban populations are exposed to a multitude of traffic-related air pollutants during daily commutes. This study assessed commuters' exposure to volatile organic compounds (VOCs) during bus, motorcycle, and bicycle commuting, and estimated the VOC inhalation dose. Benzene, toluene, ethylbenzene, and xylene (BTEX) were the main compounds detected, contributing 58 - 68% to ΣVOC (sum of the concentrations of all detected VOCs) in different travel modes. The mean ΣVOC exposure concentration was higher for motorcyclists than for cyclists and bus commuters. However, due to cyclists' higher minute ventilation rates and longer exposure time, they had the highest ΣVOC inhalation dose based on both travel time (7.09 ± 2.36 µg min-1) and distance (32.9 ± 10.8 µg km-1). Among the three travel modes, bus commuters had the lowest ΣVOC inhalation dose based on travel time (2.33 ± 1.18 µg min-1) and distance (8.91 ± 4.91 µg km-1), while motorcyclists had a moderate ΣVOC inhalation dose based on travel time (5.08 ± 1.46 µg min-1) and distance (13.4 ± 5.5 µg km-1). Health impact assessment of VOCs showed that cyclists faced the highest carcinogenic and non-carcinogenic risks, while bus commuters experienced the lowest health risk associated with VOC exposure. Our findings underscore the need to consider air quality in transportation infrastructure design and prioritize interventions to safeguard urban commuters' health, particularly cyclists, who are the most vulnerable to the adverse effects of traffic-related air pollutants.
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Contaminantes Atmosféricos , Contaminación del Aire , Compuestos Orgánicos Volátiles , Monitoreo del Ambiente , Transportes , Emisiones de Vehículos/análisis , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisisRESUMEN
Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial-mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Femenino , Células MDA-MB-231 , Fosfatidilinositol 3-Quinasas/metabolismo , Interleucina-8/genética , Interleucina-8/farmacología , Transducción de Señal , Neoplasias de la Mama/patología , Proliferación Celular , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: Coronavirus disease-2019 (COVID-19) remains a global public health concern, and remdesivir plus dexamethasone combination therapy is suggested for patients with severe disease. However, the factors associated with poor outcomes in these patients remain unclear. We identified the factors associated with poor outcomes in Taiwanese patients with severe COVID-19 treated with remdesivir plus dexamethasone. METHODS: Adults with severe COVID-19 (oxygen saturation <94% on room air or requiring supplemental oxygen) treated with remdesivir and dexamethasone were identified between 1 May and 31 July 2021. The main outcomes were 14-day non-recovery, 28-day mortality, and progression to respiratory failure requiring invasive mechanical ventilation or death in initially non-ventilated patients. The prognostic factors associated with poor outcomes were analyzed by multivariate logistic regression and Cox regression. RESULTS: Of the 110 patients treated with remdesivir and dexamethasone, 57 (51.8%) recovered within 14 days and 6 (5.5%) died within 28 days. Of the 89 initially non-ventilated patients, 12 (13.5%) progressed to respiratory failure or death. Charlson Comorbidity Index, SOFA score, and admission to remdesivir treatment interval were associated with 14-day non-recovery. C-reactive protein level was associated with 28-day mortality. Pneumonia Severity Index and admission to remdesivir treatment interval were associated with progression to respiratory failure requiring invasive mechanical ventilation or death in initially non-ventilated patients. CONCLUSION: High disease severity on admission and delayed initiation of remdesivir therapy were associated with poor outcomes in COVID-19 patients treated with remdesivir and dexamethasone.
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COVID-19 , Insuficiencia Respiratoria , Adulto , Humanos , SARS-CoV-2 , Taiwán , Pronóstico , Antivirales , Tratamiento Farmacológico de COVID-19 , Dexametasona/uso terapéutico , Insuficiencia Respiratoria/tratamiento farmacológicoRESUMEN
RATIONALE: To date, there is no actionable gene has been discovered in hepatocellular carcinoma (HCC). Tumor cells with DNA damage response and repair (DDR) gene loss-of-function mutation is sensitivity to poly-ADP-ribose polymerase (PARP) inhibitors and platinum chemotherapy in ovarian, prostate and pancreatic cancers. There is a case report demonstrated the efficacy of PARP inhibitor for BRCA2 mutation that belongs to DDR gene in HCC, which suggested the potential role of PARP inhibitor for HCC with DDR gene mutation. PATIENT CONCERNS: We reported a 44-year-old woman with non-viral HCC who was refractory to multiple treatment including target therapy, immunotherapy, and chemotherapy. The tumor tissue was submitted to next-generation sequencing using the commercially available ACTOnco®+ (ACT Genomics, Taiwan) assay that interrogates 440 and 31 cancer-related genes and fusion genes, respectively. DIAGNOSIS: A truncating mutation FANCA p.Q1307fs was also observed. The tumor was microsatellite stable and had low tumor mutational burden of 4.5 muts/Mb. INTERVENTIONS AND OUTCOMES: Given FANCA belongs to DDR genes, the inactivation evoked the idea of using PARP inhibitor and cisplatin. Therefore, the patient started to use olaparib combined with low-dose cisplatin (30 mg/m2, every 4 weeks) therapy in December 2019. Significant reduction in the tumor marker level in 1 month (PIVKA-II from 17,395 to 411 ng/dL) and follow-up CT scan showed stable disease. Her tumor did not progress until December 2020 with a progression-free survival of 12 months. LESSONS: We report the first case of FANCA-mutated HCC that responded well to olaparib and low-dose cisplatin. This addressed the potential therapeutic role of DDR gene mutation in HCC and the possible synergistic effect of PARP inhibitor and cisplatin. These findings highlight areas where further investigation and effort are needed.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adenosina Difosfato Ribosa , Adulto , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Cisplatino/uso terapéutico , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Masculino , Mutación , Ftalazinas , Piperazinas , Platino (Metal) , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
Patients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. We aimed to investigate novel dysregulated cytokines that can be used as biomarkers for infectious pleural effusions, especially for CPPE/empyema. Expression of 40 cytokines in parapneumonic effusions (PPE) was screened in the discovery phase, involving 63 patients, using a multiplex immunobead-based assay. Six cytokines were subsequently validated by enzyme-linked immunosorbent assays (ELISAs). We then used ELISA to further evaluate the diagnostic values and cutoff values of these cytokines as potential biomarkers in an expanded group that included 200 patients with uncomplicated parapneumonic effusion (UPPE), CPPE, empyema, transudates, other exudates, and malignant pleural effusion (MPE). The pleural levels of four cytokines (MIF, MIP-3α, IL-1ß, ENA-78) were highest and significantly increased in CPPE/empyema compared with those in other etiologies. According to receiver operating characteristic curve analysis, the four cytokines (MIF, MIP-3α, IL-1ß, and ENA-78) had areas under the curve (AUCs) greater than 0.710 for discriminating parapneumonic pleural effusion from noninfectious pleural effusions. In a comparison of nonpurulent CPPE with UPPE, logistic regression analysis revealed that pleural fluid MIF ≥ 12 ng/ml and MIP-3α ≥ 4.3 ng/ml had the best diagnostic value; MIF also displayed the highest odds ratio of 663 for nonpurulent CPPE, with 97.5% specificity, 94.44% sensitivity, and an AUC of 0.950. In conclusion, our results show that elevated MIF and MIP-3α may be used as novel biomarkers for PPE diagnosis, particularly in patients with CPPE/empyema; the findings indicate that dysregulated cytokine expression may provide clues about the pathogenesis of pleural infection.
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Quimiocina CCL20/análisis , Quimiocina CXCL5/análisis , Empiema Pleural/diagnóstico , Interleucina-1beta/análisis , Oxidorreductasas Intramoleculares/análisis , Factores Inhibidores de la Migración de Macrófagos/análisis , Derrame Pleural/diagnóstico , Anciano , Biomarcadores/análisis , Quimiocina CCL20/metabolismo , Quimiocina CXCL5/metabolismo , Empiema Pleural/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-1beta/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Derrame Pleural/patología , Estudios ProspectivosRESUMEN
Raw materials for traditional Chinese medicine (TCM) are often from different resources and its final product may also be made by different sites. Therefore, variabilities from different resources such as site-to-site or within site component-to-component may be expected. Consequently, test for consistency in raw materials, in-process materials, and/or final product has become an important issue in the quality control (QC) process in TCM development. In this paper, a statistical QC process for raw materials and/or the final product of TCM is proposed based on a two sided [Formula: see text]-content, [Formula: see text]-confidence tolerance interval. More specifically, we construct the tolerance interval for a random-effects model to assess the QC of TCM products from different regions and possibly different product batches. The products can be claimed to be consistency when the constructed tolerance interval is within the permitted range. Given the region and batch effects, sample sizes can also be calculated to ensure the desired measure of goodness. An example is presented to illustrate the proposed approach.
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Medicamentos Herbarios Chinos/normas , Medicina Tradicional China/normas , Proyectos de Investigación/estadística & datos numéricos , Simulación por Computador , Interpretación Estadística de Datos , Humanos , Modelos Estadísticos , Análisis Numérico Asistido por Computador , Control de Calidad , Tamaño de la MuestraRESUMEN
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach - paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses - to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA-mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.
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Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/etiología , Perfilación de la Expresión Génica , Transcriptoma , Biomarcadores de Tumor , Neoplasias Colorrectales/epidemiología , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Interferencia de ARN , ARN Mensajero/genética , Taiwán/epidemiologíaRESUMEN
The innate immune system is the frontline host protection against pathogens. Effective antiviral immunity is elicited upon recognition of viral RNAs by the host pattern recognition receptors. One of the major viral RNA sensors is retinoic acid inducible gene-1, which triggers the production of interferons (IFNs). In turn, this protective response requires another viral sensor and immunity factor interferon-inducible protein kinase RNA activator (PACT/PRKRA). Here, we report the identification and characterization of a novel antisense PACT gene that expresses a non-coding RNA in a convergent and interferon-inducible manner. Publicly available gene structure and expression data revealed that this gene, that we termed ASPACT, overlaps with the 3' -end of the PACT locus and is highly expressed during viral infection. Our results confirm the IFN-ß-inducibility of ASPACT, which is dependent on STAT-1/2. We further discovered that downregulation of ASPACT impacts both the expression and localization of the PACT transcript. At the transcription level, ChIP and ChIRP assays demonstrated that the ASPACT non-coding RNA occupies distinct chromatin regions of PACT gene and is important for promoter recruitment of the epigenetic silencer HDAC1. In parallel, ASPACT was also found to mediate nuclear retention of the PACT mRNA via direct RNA-RNA interaction, as revealed by RNA antisense purification assay. In summary, our results support the model that the non-coding RNA ASPACT acts as a negative regulator of PACT at multiple levels, and reveal a novel regulator of the viral counteractive response.
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ARN sin Sentido/metabolismo , Proteínas de Unión al ARN/metabolismo , Transducción de Señal , Núcleo Celular/metabolismo , Epigénesis Genética , Células HEK293 , Células HeLa , Histona Desacetilasa 1/metabolismo , Humanos , Inmunidad Innata , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Transcripción GenéticaRESUMEN
We report on a simple and facile synthetic approach for preparing both a CuBi2O4 photocathode and BiVO4 photoanode from a single Bi4O5I2 nanosheet template. A nanosheet structured Bi4O5I2 (nanoBi4O5I2) template, solvothermally deposited on a conducting glass substrate, can be converted to a textured CuBi2O4 photocathode and a BiVO4 photoanode with coral-like nanostructure by drop-casting a copper ion-containing and a vanadium ion-containing solution, respectively, with a follow-up heat treatment. UV-vis absorption spectra and Mott-Schottky analyses confirm CuBi2O4 and BiVO4 have well-suited band gaps for absorbing a large portion of visible light and complementary band structures for proton reduction and water oxidation, respectively. A photoelectrochemical tandem cell, consisting of a cobalt based catalyst modified CuBi2O4 photocathode and a cobalt based catalyst modified BiVO4 photoanode shows promising photoelectrochemical properties towards water splitting, and can be operated without an external bias. Factors limiting the performance of the tandem cell are also discussed.
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During neoplastic development, a multitude of changes in genome-encoded information are progressively selected to confer growth and survival advantages to tumor cells. microRNAs-mRNAs regulatory networks, given their role as a critical layer of robust gene expression control, are frequently altered in neoplasm. However, whether and how these gene perturbations impact metabolic homeostasis remains largely unresolved. Methods: Through targeted miRNA expression screening, we uncovered an oral squamous cell carcinoma (OSCC)-associated miRNAome, among which miR-31-5p was identified based on extent of up-regulation, functional impact on OSCC cell migration and invasion, and direct regulation of the rate-limiting enzyme in peroxisomal ß-oxidation, ACOX1. Results: We further found that both miR-31-5p and ACOX1 underpin, in an antagonistic manner, the overall cellular lipidome profiles as well as the migratory and invasive abilities of OSCC cells. Interestingly, the extracellular levels of prostaglandin E2 (PGE2), a key substrate of ACOX1, were controlled by the miR-31-5p-ACOX1 axis, and were shown to positively influence the extent of cell motility in correlation with metastatic status. The promigratory effect of this metabolite was mediated by an elevation in EP1-ERK-MMP9 signaling. Of note, functional significance of this regulatory pathway was further corroborated by its clinicopathologically-correlated expression in OSCC patient specimens. Conclusions: Collectively, our findings outlined a model whereby misregulated miR-31-5p-ACOX1 axis in tumor alters lipid metabolomes, consequently eliciting an intracellular signaling change to enhance cell motility. Our clinical analysis also unveiled PGE2 as a viable salivary biomarker for prognosticating oral cancer progression, further underscoring the importance of lipid metabolism in tumorigenesis.
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Acil-CoA Oxidasa/genética , Carcinogénesis/genética , Carcinoma de Células Escamosas/genética , Dinoprostona/metabolismo , MicroARNs/genética , Neoplasias de la Boca/genética , Biomarcadores de Tumor/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias de la Boca/patología , Transducción de Señal/genética , Regulación hacia Arriba/genéticaRESUMEN
In recent years, developing pharmaceutical products via multiregional clinical trials (MRCTs) has become standard. Traditionally, an MRCT would assume that a treatment effect is uniform across regions. However, heterogeneity among regions may have impact upon the evaluation of a medicine's effect. In this study, we consider a random effects model using discrete distribution (DREM) to account for heterogeneous treatment effects across regions for the design and evaluation of MRCTs. We derive an power function for a treatment that is beneficial under DREM and illustrate determination of the overall sample size in an MRCT. We use the concept of consistency based on Method 2 of the Japanese Ministry of Health, Labour, and Welfare's guidance to evaluate the probability for treatment benefit and consistency under DREM. We further derive an optimal sample size allocation over regions to maximize the power for consistency. Moreover, we provide three algorithms for deriving sample size at the desired level of power for benefit and consistency. In practice, regional treatment effects are unknown. Thus, we provide some guidelines on the design of MRCTs with consistency when the regional treatment effect are assumed to fall into a specified interval. Numerical examples are given to illustrate applications of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Modelos Estadísticos , Algoritmos , Bioestadística , Humanos , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Probabilidad , Tamaño de la Muestra , Resultado del TratamientoRESUMEN
Splitting water into hydrogen and oxygen with molecular catalysts and light has been a long-established challenge. Approaches in homogeneous systems have been met with little success and the integration of molecular catalysts in photoelectrochemical cells is challenging due to inaccessibility and incompatibility of functional hybrid molecule/material electrodes with long-term stability in aqueous solution. Here, we present the first example of light-driven water splitting achieved with precious-metal-free molecular catalysts driving both oxygen and hydrogen evolution reactions. Mesoporous TiO2 was employed as a low-cost scaffold with long-term stability for anchoring a phosphonic acid-modified nickel(ii) bis-diphosphine catalyst (NiP) for electrocatalytic proton reduction. A turnover number of 600 mol H2 per mol NiP was achieved after 8 h controlled-potential electrolysis at a modest overpotential of 250 mV. X-ray photoelectron, UV-vis and IR spectroscopies confirmed that the molecular structure of the Ni catalyst remains intact after prolonged hydrogen production, thereby reasserting the suitability of molecular catalysts in the development of effective, hydrogen-evolving materials. The relatively mild operating conditions of a pH 3 aqueous solution allowed this molecule-catalysed cathode to be combined with a molecular Fe(ii) catalyst-modified WO3 photoanode in a photoelectrochemical cell. Water splitting into H2 and O2 was achieved under solar light illumination with an applied bias of >0.6 V, which is below the thermodynamic potential (1.23 V) for water splitting and therefore allowed the storage of solar energy in the fuel H2.
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An efficient, stable and scalable hybrid photoelectrode for visible-light-driven H2 generation in an aqueous pHâ 9.2 electrolyte solution is reported. The photocathode consists of a p-type Si substrate layered with a Ti and Ni-containing composite film, which acts as both a protection and electrocatalyst layer on the Si substrate. The film is prepared by the simple drop casting of the molecular single-source precursor, [{Ti2(OEt)9(NiCl)}2] (TiNipre), onto the p-Si surface at room temperature, followed by cathodic inâ situ activation to form the catalytically active TiNi film (TiNicat). The p-Si|TiNicat photocathode exhibits prolonged hydrogen generation with a stable photocurrent of approximately -5â mA cm(-2) at 0â V vs. RHE in an aqueous pHâ 9.2 borate solution for several hours, and serves as a benchmark non-noble photocathode for solar H2 evolution that operates efficiently under neutral-alkaline conditions.
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This discussion describes a direct comparison of photoelectrochemical (PEC) water oxidation activity between a photosystem II (PSII)-functionalised photoanode and a synthetic nanocomposite photoanode. The semi-biological photoanode is composed of PSII from the thermophilic cyanobacterium Thermosynechococcus elongatus on a mesoporous indium tin oxide electrode (mesoITO|PSII). PSII embeds all of the required functionalities for light absorption, charge separation and water oxidation and ITO serves solely as the electron collector. The synthetic photoanode consists of a TiO(2) and NiO(x) coated nanosheet-structured WO(3) electrode (nanoWO(3)|TiO(2)|NiO(x)). The composite structure of the synthetic electrode allows mimicry of the functional key features in PSII: visible light is absorbed by WO(3), TiO(2) serves as a protection and charge separation layer and NiO(x) serves as the water oxidation electrocatalyst. MesoITO|PSII uses low energy red light, whereas nanoWO(3)|TiO(2)|NiO(x) requires high energy photons of blue-end visible and UV regions to oxidise water. The electrodes have a comparable onset potential at approximately 0.6 V vs. reversible hydrogen electrode (RHE). MesoITO|PSII reaches its saturation photocurrent at 0.84 V vs. RHE, whereas nanoWO(3)|TiO(2)NiO(x) requires more than 1.34 V vs. RHE. This suggests that mesoITO|PSII suffers from fewer limitations from charge recombination and slow water oxidation catalysis than the synthetic electrode. MesoITO|PSII displays a higher 'per active' site activity, but is less photostable and displays a much lower photocurrent per geometrical surface area and incident photon to current conversion efficiency (IPCE) than nanoWO(3)|TiO(2)|NiO(x_.
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Photoactive in one step! A nanocomposite water-oxidation photocatalyst was assembled by a straightforward and one-step spin-coating procedure of a Ti- and Ni-containing molecule on nanostructured WO3. The photoanode oxidizes water to O2 with good activity and stability in alkaline solution, and thereby features light absorption, charge separation and water-oxidation catalysis (see scheme).
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Recently, biosimilars have attracted much attention from sponsors and regulatory authorities, while patents on early biological products will soon expire in the next few years. The European Medicines Agency (EMEA) of the European Union (EU) published a guideline on similar biological medicinal products for approval of these products in 2005 . Based on the foundational principles of the EMEA guideline, biosimilars are expected to be similar, not identical, to the innovator biologics they seek to copy. In this article, we develop a consistency approach for assessment of similarity between a biosimilar product and the innovator biologic. A method for sample size determination for conducting a clinical trial to assess the biosimilar product is also proposed. A numerical example is given to illustrate applications of the proposed approach in different scenarios.
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Biosimilares Farmacéuticos , Modelos Estadísticos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/uso terapéutico , Aprobación de Drogas/estadística & datos numéricos , Europa (Continente) , Guías como Asunto , Tamaño de la Muestra , Equivalencia Terapéutica , Estados UnidosRESUMEN
BACKGROUND: Arm nonuse, defined as the difference between what the individual can do when constrained to use the paretic arm and what the individual does when given a free choice to use either arm, has not yet been quantified in individuals poststroke. OBJECTIVES: (1) To quantify nonuse poststroke and (2) to develop and test a novel, simple, objective, reliable, and valid instrument, the Bilateral Arm Reaching Test (BART), to quantify arm use and nonuse poststroke. METHODS: First, we quantify nonuse with the Quality of Movement (QOM) subscale of the Actual Amount of Use Test (AAUT) by subtracting the AAUT QOM score in the spontaneous use condition from the AAUT QOM score in a subsequent constrained use condition. Second, we quantify arm use and nonuse with BART by comparing reaching performance to visual targets projected over a 2D horizontal hemi-work space in a spontaneous-use condition (in which participants are free to use either arm at each trial) with reaching performance in a constrained-use condition. RESULTS: All participants (N = 24) with chronic stroke and with mild to moderate impairment exhibited nonuse with the AAUT QOM. Nonuse with BART had excellent test-retest reliability and good external validity. CONCLUSIONS: BART is the first instrument that can be used repeatedly and practically in the clinic to quantify the effects of neurorehabilitation on arm use and nonuse and in the laboratory for advancing theoretical knowledge about the recovery of arm use and the development of nonuse and "learned nonuse" after stroke.
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Brazo/fisiopatología , Terapia por Ejercicio/métodos , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/patología , Anciano , Evaluación de la Discapacidad , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Reproducibilidad de los ResultadosRESUMEN
Cobalt-containing polyoxotitanates (TiCo) are excellent precursors for the simple and scalable preparation of Nocera-type CoOx water-oxidation electrocatalysts. The TiCo cages serve as a reservoir for cobalt ions in a titania matrix on fluoride-doped tin oxide electrodes, and form, in situ, the active CoOx catalyst for O2 evolution with high stability in phosphate buffer in pH neutral water.