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Transcatheter pulmonary valve replacement (TPVR), also known as percutaneous pulmonary valve implantation, refers to a minimally invasive technique that replaces the pulmonary valve by delivering an artificial pulmonary prosthesis through a catheter into the diseased pulmonary valve under the guidance of X-ray and/or echocardiogram while the heart is still beating not arrested. In recent years, TPVR has achieved remarkable progress in device development, evidence-based medicine proof and clinical experience. To update the knowledge of TPVR in a timely fashion, and according to the latest research and further facilitate the standardized and healthy development of TPVR in Asia, we have updated this consensus statement. After systematical review of the relevant literature with an in-depth analysis of eight main issues, we finally established eight core viewpoints, including indication recommendation, device selection, perioperative evaluation, procedure precautions, and prevention and treatment of complications.
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Procedimentos Cirúrgicos Cardíacos , Valva Pulmonar , Humanos , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/cirurgia , Resultado do Tratamento , Ásia , CatéteresRESUMO
Recently, tumor budding (TB) has been suggested as a strong prognostic marker in urinary tract urothelial carcinoma (UC). The aim of this systematic review is to test the prognostic value of TB in UC by a meta-analysis of previously published studies. We systematically reviewed the literature related to TB by using the databases of Scopus, PubMed, and Web of Science. The search was limited to publications in the English language up to July 2022. There were 790 patients from 7 retrospective studies in which TB has been evaluated in UC. Two authors independently extracted the results from eligible studies. The meta-analysis of eligible studies revealed that TB is a significant prognosticator for progression-free survival in UC, with a hazard ratio (HR) of 3.51 (95% CI, 1.86-6.62; P < .001) in univariate analysis and a HR of 2.78 (95% CI, 1.57-4.93; P < .001) in multivariate analysis; a significant prognosticator for overall survival and cancer-specific survival in UC, with a HR of 3.07 (95% CI, 2.04-4.64; P < .001) and a HR of 2.18 (95% CI, 1.11-4.29; P = .02) respectively in univariate analysis. Our findings confirm that UC with a high TB count is at a high risk of progress. TB could be considered as an element in pathology reports and future oncologic staging systems.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Carcinoma de Células de Transição/patologia , Estudos RetrospectivosRESUMO
Tumor budding (TB) is a small cluster of malignant cells at the invasive front of a tumor. Despite being an adverse prognosis marker, little research has been conducted on the tumor immune microenvironment of tumor buddings, especially in cervical cancer. Therefore, RNA sequencing was performed using 21 formalin-fixed, paraffin-embedded slides of cervical tissues, and differentially expressed genes (DEGs) were analyzed. Immune Pathway and Gene Database (IMPAGT) was generated for immune profiling. "Pathway in Cancer" was identified as the most enriched pathway for both up- and downregulated DEGs. Kyoto Encyclopedia of Genes and Genomes Mapper and Gene Ontology further revealed the activation of the PI3K/Akt signaling pathway. An IMPAGT analysis revealed immune dysregulation even at the tumor budding stage, especially in the PI3K/Akt/mTOR axis, with a high efficiency and integrity. These findings emphasized the clinical significance of tumor buddings and the necessity of blocking the overactivation of the PI3K/Akt/mTOR pathway to improve targeted therapy in cervical cancer.
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Depolymerization of lignin is an important step to obtain a lignin monomer for the synthesis of functional chemicals. In the context of more lignin produced from biomass and pulp industry, converting real lignin with low purity is still required more studies. In this study, the influence of solvent composition and reaction parameters such as binary solvents ratio, time, and temperature, the solvent-to-lignin ratio on the depolymerization of rice straw lignin was investigated carefully. Essential lignin-degraded products including liquid product (LP), char (solid), and gas were obtained, and their yields were directly influenced by reaction conditions. Results show that the maximum lignin conversion rate of 92% and LP yield of 66% was under the condition of 275°C, 30 min, 75 : 1 (mL solvent/1 g lignin), and ethanol 50%. Gas chromatography-mass spectroscopy (GC-MS) analysis was used for the analysis of the depolymerization products and identified 11 compounds which are mainly phenolic compounds such as 2-ethylphenol, 3-ethylphenol, phenol, methyl 2,4,6-trimethylbenzoate. The structure changes of LP and char in various conditions were analyzed using Fourier-transform infrared (FTIR).
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Lignina , Oryza , Biomassa , Etanol/química , Lignina/química , Solventes/químicaRESUMO
The smart grid is one of the core technologies that enable sustainable economic and social developments. In recent years, various cyber attacks have targeted smart grid systems, which have led to severe, harmful consequences. It would be challenging to build a real smart grid system for cybersecurity experimentation and validation purposes. Hence, analytical techniques, with simulations, can be considered as a practical solution to make smart grid cybersecurity experimentation possible. This paper first provides a literature review on the current state-of-the-art in smart grid attack analysis. We then apply graphical security modeling techniques to design and implement a Cyber Attack Analysis Framework for Smart Grids, named GridAttackAnalyzer. A case study with various attack scenarios involving Internet of Things (IoT) devices is conducted to validate the proposed framework and demonstrate its use. The functionality and user evaluations of GridAttackAnalyzer are also carried out, and the evaluation results show that users have a satisfying experience with the usability of GridAttackAnalyzer. Our modular and extensible framework can serve multiple purposes for research, cybersecurity training, and security evaluation in smart grids.
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Segurança Computacional , Sistemas ComputacionaisRESUMO
Bdellovibrio and like organisms are abundant environmental parasitoids of prokaryotes that show diverse predation strategies. The vast majority of studied Bdellovibrio bacteria and like organisms deploy intraperiplasmic replication inside the prey cell, while few isolates with smaller genomes consume their prey from the outside in an epibiotic manner. The novel parasitoid "Candidatus Bdellovibrio qaytius" was isolated from a eutrophic freshwater pond in British Columbia, where it was a continual part of the microbial community. "Ca Bdellovibrio qaytius" was found to preferentially prey on the betaproteobacterium Paraburkholderia fungorum without entering the periplasm. Despite its epibiotic replication strategy, "Ca Bdellovibrio" encodes a large genomic complement more similar to that of complex periplasmic predators. Functional genomic annotation further revealed several biosynthesis pathways not previously found in epibiotic predators, indicating that "Ca Bdellovibrio" represents an intermediate phenotype and at the same time narrowing down the genomic complement specific to epibiotic predators. In phylogenetic analysis, "Ca Bdellovibrio qaytius" occupies a widely distributed, but poorly characterized, basal cluster within the genus Bdellovibrio This suggests that epibiotic predation might be a common predation type in nature and that epibiotic predation could be the ancestral predation type in the genus.IMPORTANCEBdellovibrio and like organisms are bacteria that prey on other bacteria and are widespread in the environment. Most of the known Bdellovibrio species enter the space between the inner and outer prey membrane, where they consume their prey cells. However, one Bdellovibrio species has been described that consumes its prey from the outside. Here, we describe "Ca Bdellovibrio qaytius," a novel member of the genus Bdellovibrio that also remains outside the prey cell throughout its replication cycle. Unexpectedly, the genome of "Ca Bdellovibrio" is much more similar to the genomes of intracellular predators than to the species with a similar life cycle. Since "Ca Bdellovibrio" is also a basal representative of this genus, we hypothesize that extracellular predation could be the ancestral predation strategy.
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Bdellovibrio/genética , Bdellovibrio/classificação , Bdellovibrio/isolamento & purificação , Bdellovibrio/fisiologia , Burkholderiaceae/fisiologia , Genoma Bacteriano , Genômica , Filogenia , Lagoas/microbiologiaRESUMO
BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford.
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Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Doença de Mão, Pé e Boca/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiologia , Doenças do Sistema Nervoso Autônomo/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Método Duplo-Cego , Feminino , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Lactente , Sulfato de Magnésio/efeitos adversos , Masculino , PlacebosRESUMO
BACKGROUND: Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole-genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV-A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. RESULTS: Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. CONCLUSIONS: In conclusion, we have successfully developed a non-ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples.
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Enterovirus Humano A/isolamento & purificação , Doença de Mão, Pé e Boca/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase/métodos , Enterovirus Humano A/classificação , Enterovirus Humano A/genética , Genótipo , Doença de Mão, Pé e Boca/diagnóstico , Humanos , Filogenia , SorotipagemRESUMO
PURPOSE: Severe chordee with hypospadias may require repair by ventral corporoplasty with a free graft before urethroplasty. We report an 11 year experience with one-stage and two-stage hypospadias repair using dermal grafts. MATERIALS AND METHODS: From 12/1997 to 12/2008, 47 hypospadias with severe chordee were repaired using a ventral dermal graft to correct the chordee. Forty cases were repaired in two stages; the remaining seven patients had adequate preputial skin and were repaired in one stage. In 28 cases the neourethra was covered with both tunica vaginalis and penile dartos flap while 12 were covered only with penile dartos flap. Patients ranged from 12 to 152 months of age. Follow-up ranged from 6 months to 4 years. RESULTS: 28 patients with both tunica vaginalis and dartos flap had 7 urethral fistulas and 2 developed meatal stenosis. 12 patients with only penile dartos flap had 3 fistulas and 2 had meatal regression. The seven patients who underwent a one-stage repair had good results with a straight penis and no evidence of urethral fistula or urethral stenosis. CONCLUSIONS: Dermal graft can be performed in one or two stage hypospadias repair. Complication rates are similar to other standard repairs for proximal hypospadias.
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Hipospadia/cirurgia , Pênis/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Masculino , Índice de Gravidade de Doença , Retalhos Cirúrgicos , Resultado do Tratamento , Vietnã , CicatrizaçãoRESUMO
For the first time quantitative measurements of the hydroperoxyl radical (HO2) in a jet-stirred reactor were performed thanks to a new experimental setup involving fast sampling and near-infrared cavity ring-down spectroscopy at low pressure. The experiments were performed at atmospheric pressure and over a range of temperatures (550-900 K) with n-butane, the simplest hydrocarbon fuel exhibiting cool flame oxidation chemistry which represents a key process for the auto-ignition in internal combustion engines. The same technique was also used to measure H2O2, H2O, CH2O, and C2H4 under the same conditions. This new setup brings new scientific horizons for characterizing complex reactive systems at elevated temperatures. Measuring HO2 formation from hydrocarbon oxidation is extremely important in determining the propensity of a fuel to follow chain-termination pathways from R + O2 compared to chain branching (leading to OH), helping to constrain and better validate detailed chemical kinetics models.
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OBJECTIVES: We aim to study the pattern of aortic dilatation in different BAV phenotypes and to find any correlations between aortic dilatation, aortic elasticity and AS and/or AR in our local population. METHODS: All BAV patients and controls were retrospectively studied. Aortic distensibility and stiffness index of the ascending aorta were calculated. RESULTS: A total of 191 patients with BAV and 180 controls were enrolled. Aortic dilatation involving a single site was more common with dilatation involving only the ascending aorta (R-N phenotype) and aortic root (N-L phenotype). AR was most common in patients with N-L and R-L phenotypes and AS in R-N phenotype. Aortic elasticity had no correlation with the different BAV phenotypes. CONCLUSIONS: There are different patterns of aortic dilatation in different BAV phenotypes, which may further contribute to the development of aortic stenosis or regurgitation. Aortic elasticity is independent of the BAV phenotypes and is impaired in BAV patients regardless of AS or AR severity.
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Valva Aórtica/anormalidades , Elasticidade , Cardiopatias Congênitas , Doenças das Valvas Cardíacas , Adulto , Idoso , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Doença da Válvula Aórtica Bicúspide , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/fisiopatologia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , UltrassonografiaRESUMO
In RNA-seq data analysis, condensing the gene count matrix size is pivotal for downstream investigations, particularly pathway analysis. For this purpose, harnessing machine learning attracts increasing interest, while conventional methodologies depend on p-value comparisons. In this study, 20 tissue samples from real-world cervical cancers were subjected to sequencing, followed by the application of the Mclust algorithm to delineate an optimal cluster. By stratifying tumor budding into high and low groups and quantifying the epithelial-to-mesenchymal transition (EMT) score to scrutinize tumor budding, we discerned 24 EMT-related genes, with 5 showing strong associations with cervical cancer prognosis. Our observations elucidate a biological flow wherein EMT, Matrix Metallopep-tidase 2 (MMP2), and extracellular matrix (ECM) degradation are interconnected, ultimately leading to collagen type VI and exacerbating the prognosis of cervical cancer. The present study underscores an alternative method for selecting useful EMT-related genes by employing an appropriate clustering algorithm, thereby avoiding classical methods while unveiling novel insights into cervical cancer etiology and prognosis. Moreover, when comparing high and low tumor budding, collagen type VI emerges as a potential gene marker for the prognosis of cervical cancer.
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Ovarian cancer (OC) presents a global health challenge, with well-documented genetic aspects. However, to the best of our knowledge, the role of human papillomavirus (HPV) types 16 and 18 in OC remains unclear. The present meta-analysis assessed the prevalence of HPV in OC across 43 studies and included a comparative meta-analysis of 19 case-control studies to determine the association of HPV with OC risk. Subgroup analyses were performed based on geographic regions and histopathological types to explore heterogeneity, and publication bias was evaluated using funnel plots and statistical tests of asymmetry. The pooled prevalence of HPV was found to be 10% (95% CI, 5-18) and 7% (95% CI, 3-15) specifically for HPV 16/18. Case-control studies indicated an odds ratio (OR) of 4.92 (95% CI, 1.96-12.53) for HPV 16/18, with higher pooled prevalence rates of 17% for all HPV genotypes and 13% for HPV 16/18. Notably, Asian countries exhibited the highest HPV prevalence and OR in OC. These findings support the involvement of HPV, particularly HPV 16 and 18, in increasing the risk of OC, emphasizing the need for further research to confirm these associations and explore potential mechanisms.
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There is limited information regarding the influence of mangrove growth on the morphological evolution of intertidal mudflats. In this study, Tan Phu Dong district, Tien Giang Province, Vietnam, was selected for investigating how mangrove growth influenced the morphological evolution of an intertidal mudflat. The authors analyzed a series of satellite images (from 1995 and 2022), calculated the enhanced vegetation index (EVI), and documented field visits and observations in pursuit of the objective of the study. The findings revealed that fine-grained sediment accumulated as unconsolidated substratum (US) in the first step of the morphological evolution of the intertidal mudflat, with sediment accumulation of 910 ha in 1995. The US provided favorable conditions for mangroves to grow, while mangrove growth helped compact the US into a compact substratum (CS) in addition to promoting continuous sediment accumulation, increased the vegetation cover of the island, and elevated the substrate density of the remaining areas. As a result, the US and CS decreased steadily between 1995 and 2020, from 910 ha in 1995 to 401 ha in 2020 and from 433 ha in 2005 to 111 ha in 2020, respectively. Meanwhile, the low-vegetation area (LVA), medium-vegetation area (MVA), and high vegetation area (HVA) gradually increased between 1995 and 2015, from 0 ha in 1995 to 104 ha in 2015, from 0 ha in 1995 to 96 ha in 2015, and from 0 ha in 1995 to 114 ha in 2015, respectively. However, the LVA decreased slightly between 2015 and 2020 due to significant sand accumulation, which significantly killed the mangrove trees. In contrast, the MVA and HVA steadily increased between 2015 and 2020, from 96 ha in 2015 to 116 ha in 2020 and from 114 ha in 2015 to 221 ha in 2020, respectively. In 2022, there was a steady increase in HVA (298 ha in 2022), although the date of the 2022 satellite retrieval was 28 January 2022. This study recommends that the technical design of the existing coastal protection works should be revised or adapted to take account of sediment accumulation as the first step in the morphological evolution of the examined intertidal mudflat, rather than mangrove growth.
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BACKGROUND/AIM: To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy. MATERIALS AND METHODS: Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package. RESULTS: Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score: 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55. CONCLUSION: The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina , Compostos Bicíclicos Heterocíclicos com Pontes , Sinergismo Farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Sulfonamidas , Humanos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Jurkat , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Cervical adenocarcinoma (AC), a subtype of uterine cervical cancer (CC), poses a challenge due to its resistance to therapy and poor prognosis compared with squamous cervical carcinoma. Streptococcus agalactiae [group B Streptococcus (GBS)], a Gram-positive coccus, has been associated with cervical intraepithelial neoplasia in CC. However, the underlying mechanism interaction between GBS and CC, particularly AC, remains elusive. Leveraging The Cancer Genome Atlas public data and time-series transcriptomic data, the present study investigated the interaction between GBS and AC, revealing activation of two pivotal pathways: 'MAPK signaling pathway' and 'mTORC1 signaling'. Western blotting, reverse transcription-quantitative PCR and cell viability assays were performed to validate the activation of these pathways and their role in promoting cancer cell proliferation. Subsequently, the present study evaluated the efficacy of two anticancer drugs targeting these pathways (binimetinib and ridaforolimus) in AC cell treatment. Binimetinib demonstrated a cytostatic effect, while ridaforolimus had a modest impact on HeLa cells after 48 h of treatment, as observed in both cell viability and cytotoxicity assays. The combination of binimetinib and ridaforolimus resulted in a significantly greater cytotoxic effect compared to binimetinib or ridaforolimus monotherapy, although the synergy score indicated an additive effect. In general, the MAPK and mTORC1 signaling pathways were identified as the main pathways associated with GBS and AC cells. The combination of binimetinib and ridaforolimus could be a potential AC treatment.
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The reasons for sex-associated gut microbiota differences have not been determined, and although sex hormones, diet, and other factors are considered to contribute to them, many of these factors are age related. To shed light on this complex interplay, our study aimed to investigate and compare the gut microbial compositions of males and females across a broad range of ages, aiming to identify sex-associated disparities and potential causal factors. Our study encompassed a comprehensive analysis of gut microbiota data obtained from 444 Japanese individuals, ranging from newborns to centenarians, sourced from the DNA Data Bank of Japan. We categorized the subjects into 13 distinct age groups and examined their relative microbial abundances, as well as alpha and beta diversities, in relation to sex and age. No difference was observed between gut microbiota relative abundances or alpha diversities between men and women at any age. However, the study showed that the heterogeneity of gut microbiota among women in their 20s was greater than in men. To confirm the general occurrence of this difference, we conducted additional analyses using seven datasets: three from Japan and four from other countries. Interestingly, this variance was particularly noticeable within Japanese women. We also showed a potential link between the observed heterogeneity and dietary fiber intake. It is hoped this study will provide clues that aid in the identification of factors responsible for sex-associated differences in gut microbiota compositions.
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BACKGROUND/AIM: This study evaluated the possibility of clinical use of circulating-tumor DNA (ctDNA) as a biomarker to determine up-front autologous stem cell transplantation (auto-SCT) for patients with high-risk diffuse large B-cell lymphoma (DLBCL) in practice. PATIENTS AND METHODS: To explore the dynamics of ctDNA in DLBCL, blood samples were collected sequentially before and after treatment from patients with newly diagnosed DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. To conduct ctDNA genotyping and ctDNA monitoring simultaneously, targeted sequencing by cancer personalized profiling using deep sequencing was used. RESULTS: Ten patients between the ages of 50 and 60 years were enrolled. Based on the international prognostic index (IPI), seven patients were classified as high-IPI-risk group, and three patients were classified as low-IPI-risk group. The IPI risk group correlated with total metabolic tumor volume. All patients completed six cycles of R-CHOP chemotherapy, and seven patients achieved complete response. Changes in ctDNA mutation numbers did not correlate with changes in PET scan images and treatment response. In most high-risk patients, new mutations appeared in ctDNA after completion of chemotherapy that conceivably marked resistant clones. Notably, disease relapse did not occur in high-risk patients with poor prognostic mutations who underwent autologous SCT. CONCLUSION: ctDNA monitoring was meaningful in high-risk patients. Moreover, ctDNA and well-known prognostic factors should be considered in the decision making for auto-SCT. If a new genetic mutation in ctDNA with a negative prognosis would emerge during treatment, high-risk patients should consider auto-SCT.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Recidiva Local de Neoplasia/tratamento farmacológico , Transplante Autólogo , Transplante de Células-Tronco , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Prognóstico , Ciclofosfamida/uso terapêutico , Prednisona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/uso terapêutico , Doxorrubicina/efeitos adversos , Vincristina/uso terapêutico , DNARESUMO
In the adsorption process for wastewater treatment, the adsorbent plays an important role. A composite adsorptive material composed of graphitic carbon nitride and agar-derived porous carbon (CNPC) was fabricated from simple precursors (melamine, thiourea, and agar) and through a facile procedure with different melamine and thiourea ratios. Characterization of CNPC proved a successful formation of a porous structure consisting of mesopores and macropores, wherein CNPC holds distinctive electrochemical (lowered resistance and higher specific capacity) and photochemical properties (lowered bandgap to 2.33â¯eV) thanks to the combination of graphitic carbon nitride (CN) and agar-derived porous carbon (PC). Inheriting the immanent nature, CNPC was subjected to the adsorption of methylene blue (MB) dye in an aqueous solution. The highest adsorption capacity was 133â¯mg/g for CNPC-4 which was prepared using a melamine to thiourea ratio of 4:4 - equivalent to the removal rate of 53.2â¯% and following the pseudo-I-order reaction rate. The effect of pH points out that pHâ¯7 and 9 were susceptible to maximum removal and pretreatment is not required while the optimal ratio of 7.5â¯mg of MB and 30â¯mg of material was also determined to yield the highest performance. Furthermore, the reusability of the material for three consecutive cycles was evaluated based on two methods pyrolysis at 200⯰C and photocatalytic degradation by irradiation under visible light. In general, the photocatalytic regeneration pathway is more ample and efficient than pyrolysis in terms of energy efficiency (saving energy over 10 times) and adsorption capacity stability. As a whole, the construction of accessible regenerative and stable adsorbent could be a venturing step into the sustainable development spearhead for industries.