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1.
J Colloid Interface Sci ; 676: 72-79, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-39018812

RESUMEN

Due to the sensitivity to water, the all-inorganic CsPbBr3 nanocrystals have been widely applied in information encryption with spatial dimensions. However, the absence of time-dimension information limits the information capacity for the application of CsPbBr3. In this work, the CsPbBr3 nanocrystal was combined with water-sensitive borophosphate glass, achieving decomposing/recrystallization of CsPbBr3 nanocrystal with multi-dimension. The addition of SiO2 confirms that the collapse of the borophosphate glass network structure causes the exposure of the CsPbBr3 nanocrystals. The decomposition and recrystallization mechanism of CsPbBr3 nanocrystals in glass-ceramics upon encountering water has been verified. Finally, an information encryption strategy, using the mixture of CsPbBr3 glass ceramic and sodium carboxymethylcellulose as ink, is designed via adopting screen-printing technology, which not only provides a new idea for the preparation of CsPbBr3 nanocrystals, but also establish a new avenue for the information encryption technology.

2.
Materials (Basel) ; 17(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38930337

RESUMEN

Steel slag as an alkaline industrial solid waste, possesses the inherent capacity to engage in carbonation reactions with carbon dioxide (CO2). Capitalizing on this property, the current research undertakes a systematic investigation into the fabrication of high-carbonation precast concrete (HCPC). This is achieved by substituting a portion of the cementitious materials with steel slag during the carbonation curing process. The study examines the influence of varying water-binder ratios, silica fume dosages, steel slag dosages, and sand content on the compressive strength of HCPC. Findings indicate that adjusting the water-binder ratio to 0.18, adding 8% silica fume, and a sand volume ratio of 40% can significantly enhance the compressive strength of HCPC, which can reach up to 104.9 MPa. Additionally, the robust frost resistance of HCPC is substantiated by appearance damage analysis, mass loss rate, and compressive strength loss rate, after 50 freeze-thaw cycles the mass loss, and the compressive strength loss rate can meet the specification requirements. The study also corroborates the high-temperature stability of HCPC. This study optimized the preparation of HCPC and provided a feasibility for its application in precast concrete.

3.
Nat Commun ; 15(1): 5288, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902277

RESUMEN

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.


Asunto(s)
Canales Iónicos Sensibles al Ácido , Péptido Relacionado con Gen de Calcitonina , Ratones Noqueados , Psoriasis , Células Receptoras Sensoriales , Animales , Canales Iónicos Sensibles al Ácido/metabolismo , Canales Iónicos Sensibles al Ácido/genética , Femenino , Psoriasis/metabolismo , Psoriasis/patología , Psoriasis/genética , Psoriasis/inducido químicamente , Ratones , Péptido Relacionado con Gen de Calcitonina/metabolismo , Péptido Relacionado con Gen de Calcitonina/genética , Células Receptoras Sensoriales/metabolismo , Piel/metabolismo , Piel/patología , Imiquimod , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Inflamación/metabolismo , Inflamación Neurogénica/metabolismo , Humanos , Nociceptores/metabolismo , Interleucina-23/metabolismo , Interleucina-23/genética
4.
Heliyon ; 10(11): e32018, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38867969

RESUMEN

Ferroptosis, a cell death pathway dependent on iron, has been shown in research to play a role in the development, advancement, and outlook of tumours through ferroptosis-related lncRNAs (FRLRs). However, the value of the FRLRs in bladder cancer (BLCA) has not been thoroughly investigated. This research project involved developing a predictive model using ten specific FRLRs (AC099850.4, AL731567.1, AL133415.1, AC021321.1, SPAG5-AS1, HMGA2-AS1, RBMS3-AS3, AC006160.1, AL583785.1, and AL662844.4) through univariate COX and LASSO regression techniques. The validation of this signature as a standalone predictor was confirmed in a group of 65 patients from the urology bladder tumour database at the First Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. Patients were categorized based on their median risk score into either a low-risk group or a high-risk group. Enrichment analysis identified possible molecular mechanisms that could explain the variations in clinical outcomes observed in high-risk and low-risk groups. Moreover, we explored the correlation between FLPS and immunotherapy-related indicators. The ability of FLPS to forecast the effectiveness of immunotherapy was validated by the elevated levels of immune checkpoint genes (PD-L1, CTLA4, and PD-1) in the group at high risk. We also screened the crucial FRLR (HMGA2-AS1) through congruent expression and prognostic conditions and established a ceRNA network, indicating that HMGA2-AS1 may affect epithelial-mesenchymal transition by modulating the Wnt signalling pathway through the ceRNA mechanism. We identified the top five mRNAs (NFIB, NEGR1, JAZF1, JCAD, and ESM1) based on random forest algorithm and analysed the relationship between HMGA2-AS1, the top five mRNAs, and immunotherapy, and their interactions with drug sensitivities. Our results suggest that patients with BLCA have a greater sensitivity to four drugs (dasatinib, pazopanib, erismodegib and olaparib). Our study provides new insights into the TME, key signalling pathways, genome, and potential therapeutic targets of BLCA, with future guidance for immunotherapy and targeted precision drugs.

5.
Autism Res ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925611

RESUMEN

Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and communication. This study aims to delineate ASD subtypes based on individual gray matter brain networks and provide new insights from a graph theory perspective. In this study, we extracted and normalized single-subject gray matter networks and calculated each network's topological properties. The heterogeneity through discriminative analysis (HYDRA) method was utilized to subtype all patients based on network properties. Next, we explored the differences among ASD subtypes in terms of network properties and clinical measures. Our investigation identified three distinct ASD subtypes. In the case-control study, these subtypes exhibited significant differences, particularly in the precentral gyrus, lingual gyrus, and middle frontal gyrus. In the case analysis, significant differences in global and nodal properties were observed between any two subtypes. Clinically, subtype 1 showed lower VIQ and PIQ compared to subtype 3, but exhibited higher scores in ADOS-Communication and ADOS-Total compared to subtype 2. The results highlight the distinct brain network properties and behaviors among different subtypes of male patients with ASD, providing valuable insights into the neural mechanisms underlying ASD heterogeneity.

6.
Front Artif Intell ; 7: 1401810, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887604

RESUMEN

Introduction: Regulatory agencies generate a vast amount of textual data in the review process. For example, drug labeling serves as a valuable resource for regulatory agencies, such as U.S. Food and Drug Administration (FDA) and Europe Medical Agency (EMA), to communicate drug safety and effectiveness information to healthcare professionals and patients. Drug labeling also serves as a resource for pharmacovigilance and drug safety research. Automated text classification would significantly improve the analysis of drug labeling documents and conserve reviewer resources. Methods: We utilized artificial intelligence in this study to classify drug-induced liver injury (DILI)-related content from drug labeling documents based on FDA's DILIrank dataset. We employed text mining and XGBoost models and utilized the Preferred Terms of Medical queries for adverse event standards to simplify the elimination of common words and phrases while retaining medical standard terms for FDA and EMA drug label datasets. Then, we constructed a document term matrix using weights computed by Term Frequency-Inverse Document Frequency (TF-IDF) for each included word/term/token. Results: The automatic text classification model exhibited robust performance in predicting DILI, achieving cross-validation AUC scores exceeding 0.90 for both drug labels from FDA and EMA and literature abstracts from the Critical Assessment of Massive Data Analysis (CAMDA). Discussion: Moreover, the text mining and XGBoost functions demonstrated in this study can be applied to other text processing and classification tasks.

7.
Surgery ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38890101

RESUMEN

BACKGROUND: This study aimed to observe the occurrence of recurrent laryngeal nerve injury after McKeown esophagectomy for esophageal squamous cell carcinoma, as well as its recovery and influencing factors within 7 months after surgery. METHODS: From July 2020 to July 2021, among all patients who underwent minimally invasive McKeown esophagectomy, 90 patients who developed vocal cord paralysis after surgery were included in the study. These patients underwent endoscopic vocal cord function assessment every 1 to 2 months and continued until 7 months postoperatively. RESULTS: Among all 388 patients undergoing esophagectomy, 23.2% (90/388) of patients suffered postoperative vocal cord paralysis. Left, right, and bilateral injuries were confirmed in 73 (81.1%), 12 (13.3%), and 5 patients (5.6%), respectively. With a median recovery time being 183 days, the cumulative overall recovery rate was 65.4% at 7 months, 68.6% for the left side, 55.6% for the right, and 20.0% for bilateral injuries. In multivariable analysis, cervical paraoesophageal lymph node dissection and conventional thoracoscopic-assisted esophagectomy were demonstrated to be independent risk factors associated with non-recovery of vocal cord paralysis. CONCLUSIONS: After intensive endoscopic follow-up, a cumulative vocal cord paralysis recovery rate of 65.4% within 7 months was observed in patients after minimally invasive McKeown esophagectomy. Cervical paraoesophageal lymph node dissection and conventional thoracoscopic-assisted esophagectomy were demonstrated to be risk factors hindering vocal cord paralysis recovery.

8.
J Thorac Dis ; 16(5): 2948-2962, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38883642

RESUMEN

Background: Esophageal cancer remains a significant burden of lethal cancers worldwide, particularly in China. This is an annual report of Shanghai Chest Hospital (SCH) on surgical treatment for esophageal cancer patients in 2017. Methods: All patients who received surgical treatment for esophageal cancer at SCH in 2017 were given a detailed summary of clinical information based on the database of SCH. Kaplan-Meier method was used to present their survival, subgroup analyses, and multivariate Cox regression analysis were used to estimate the potential risk factors for prognosis. Results: In 2017, a total of 663 patients received surgical treatment (628 esophagectomies and 35 endoscopic resections) for esophageal cancer at SCH. Of the patients who underwent esophagectomy, 292 patients received perioperative treatment, majority of which was postoperative treatment (47.9%). Only 69 (10.4%) patients received preoperative treatment. Minimally invasive techniques were used in 444 (70.7%) patients and robotic-assisted esophagectomies were used in 130 (20.7%) patients. Complete resection (R0) was achieved in 90.3% of esophagectomy patients. The 5-year overall survival (OS) rate after esophagectomy was 52.5%. Conclusions: The 5-year OS of patients with esophageal cancer can reach 52.5% after surgical treatment in 2017 at SCH. The exact beneficiaries of neoadjuvant therapy are still unclear in the 2017 cohort.

9.
EMBO J ; 43(12): 2453-2485, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38719994

RESUMEN

Double-strand breaks (DSBs) are the most lethal form of DNA damage. Transcriptional activity at DSBs, as well as transcriptional repression around DSBs, are both required for efficient DNA repair. The chromatin landscape defines and coordinates these two opposing events. However, how the open and condensed chromatin architecture is regulated remains unclear. Here, we show that the GATAD2B-NuRD complex associates with DSBs in a transcription- and DNA:RNA hybrid-dependent manner, to promote histone deacetylation and chromatin condensation. This activity establishes a spatio-temporal boundary between open and closed chromatin, which is necessary for the correct termination of DNA end resection. The lack of the GATAD2B-NuRD complex leads to chromatin hyperrelaxation and extended DNA end resection, resulting in homologous recombination (HR) repair failure. Our results suggest that the GATAD2B-NuRD complex is a key coordinator of the dynamic interplay between transcription and the chromatin landscape, underscoring its biological significance in the RNA-dependent DNA damage response.


Asunto(s)
Cromatina , Roturas del ADN de Doble Cadena , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2 , Cromatina/metabolismo , Cromatina/genética , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/metabolismo , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , ARN/metabolismo , ARN/genética , Daño del ADN , ADN/metabolismo , ADN/genética , Animales , Humanos , Transcripción Genética , Reparación del ADN , Ratones
10.
Biochem Pharmacol ; 225: 116282, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38762147

RESUMEN

IPF is a chronic, progressive, interstitial lung disease with high mortality. Current drugs have limited efficacy in curbing disease progression and improving quality of life. Selpercatinib, a highly selective inhibitor of receptor tyrosine kinase RET (rearranged during transfection), was approved in 2020 for the treatment of a variety of solid tumors with RET mutations. In this study, the action and mechanism of Selpercatinib in pulmonary fibrosis were evaluated in vivo and in vitro. In vivo experiments demonstrated that Selpercatinib significantly ameliorated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro, Selpercatinib inhibited the proliferation, migration, activation and extracellular matrix deposition of fibroblasts by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathway, and suppressed epithelial-mesenchymal transition (EMT) like process of lung epithelial cells via inhibiting TGF-ß1/Smad pathway. The results of in vivo pharmacological tests corroborated the results obtained from the in vitro experiments. Further studies revealed that Selpercatinib inhibited abnormal phenotypes of lung fibroblasts and epithelial cells in part by regulating its target RET. In short, Selpercatinib inhibited the activation of fibroblasts and EMT-like process of lung epithelial cells by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathways, thus alleviating BLM-induced pulmonary fibrosis in mice.


Asunto(s)
Bleomicina , Ratones Endogámicos C57BL , Fibrosis Pulmonar , Transducción de Señal , Factor de Crecimiento Transformador beta1 , Animales , Bleomicina/toxicidad , Factor de Crecimiento Transformador beta1/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/prevención & control , Masculino , Pirazoles/farmacología , Pirazoles/uso terapéutico , Piridinas/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo
11.
Small Methods ; : e2400224, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697931

RESUMEN

The pursuit of high energy densities propels the design of next-generation nickel-based layered oxide cathodes. The utilization of low-cobalt, ultrahigh-nickel layered oxide cathodes, and the extension of operating voltages promise enhanced energy density. However, stability and safety face challenges associated with nickel content, including structural degradation, lattice oxygen evolution, and thermal instability. In this study, a promising strategy of Al and Nb dual-bulk-doping is presented in high-Ni cathode materials of LiNi0.96Co0.04O2 (NC) to stabilize the bulk structure, suppress oxygen release, and attain superior electrochemical performance at high voltages. The introduction of Al and Nb effectively raises the migration energy of Ni2+ into Li sites and stabilizes lattice oxygen through strengthened Al─O and Nb─O bonds. Furthermore, the substitution of high-valence Nb ions reduces the charge depletion of lattice oxygen and induces an ordered microstructure. The Al and Nb dual-bulk-doping strategy mitigates strain and stress associated with the H2↔H3 phase transition, reducing the generation and propagation of microcracks. The resulting Li(Ni0.96Co0.04)0.985Al0.01Nb0.005O2 (NCAN) cathode exhibits superior cycling stability, with a capacity retention of 77.8% after 300 cycles, even when operating at a high-voltage of 4.4 V, outperforming the NC (48.5%). This work provides a promising perspective for developing high-voltage and high-Ni cathode materials.

12.
Sci Total Environ ; 933: 173007, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38740206

RESUMEN

Dexamethasone (DEX) is a hormone drug that is often detected in wastewater treatment plants, but its impact on activated sludge systems is unknown. This study explored the long-term effects of DEX on nutrient removal, microbial activities, microbial assembly, and microbial interactions in the activated sludge system. During the 90-day DEX exposure experiment, both chemical oxygen demand and total nitrogen removal efficiencies were initially inhibited and then recovered. Microbial activities, i.e., specific oxygen uptake rate and denitrification, did not differ significantly from that of the control reactor (p > 0.05), possibly due to the secretion of extracellular polymers that act as a protective barrier against excess reactive oxygen species induced by DEX. This barrier protects cell membrane integrity and ensures stable treatment performance. Analysis of microbial assembly identified the drift of stochastic processes (from 92.7 % to 51.8 %) and homogeneous selection of deterministic processes (from 1.6 % to 38.7 %) as the main driving forces of microbial community structure succession under long-term DEX stress. Although long-term exposure to 1000 µg/L DEX did not significantly increase the abundance levels of functional bacteria (Nitrosomonas and 996-1) and key genes (AmoCAB and Hao), the ammonia oxidation capacity of the activated sludge system was enhanced. Analysis of microbial interactions indicated that streamlining of functional subnetworks and increased cooperation were the primary reasons. This is the first study to explore the long-term effects of DEX on activated sludge and provide insights into microbial interaction and assembly. Moreover, the findings of this study broaden our knowledge and lay an experimental foundation for reducing risks associated with hormone drugs.


Asunto(s)
Dexametasona , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas del Alcantarillado/microbiología , Dexametasona/farmacología , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos/microbiología , Contaminantes Químicos del Agua , Aguas Residuales
13.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38763767

RESUMEN

The canalis sinuosus, a canal containing the anterior superior alveolar nerve bundle, originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla. It was once regarded as an anatomical variation. However, with the widespread application of cone beam computed tomography (CBCT), the detection rate of canalis sinuosus in the population has increased. The canalis sinuosus exhibits diverse courses, branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region, with the majority traversing the palatal side of the central incisor. The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth, their corresponding soft tissues, and the maxillary sinus mucosa, but also relates to the nasal septum, lateral nasal wall, and parts of the palatal mucosa. To minimize surgical complications, implantologists need to investigate strategies for preventing and treating canalis sinuosus injuries. Preoperatively, implantologists should use CBCT to identify the canalis sinuosus and virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus. Intraoperatively, implantologists should assess bleeding and patient comfort, complemented by precision surgical techniques such as the use of implant surgical guide plates. Postoperatively, CBCT can be employed to examine the relationship between the implant and the canalis sinuosus, and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms. This review summarizes the detection of canalis sinuosus in the population, its anatomical characteristics, and its physiological functions in the anterior maxilla, and discusses strategies for effectively avoiding canalis sinuosus injuries during implant surgery, thereby enhancing implantologists' awareness and providing references for clinical decision-making.

14.
Nat Commun ; 15(1): 3700, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697989

RESUMEN

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.


Asunto(s)
Biomarcadores de Tumor , Variaciones en el Número de Copia de ADN , Metilación de ADN , Detección Precoz del Cáncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/diagnóstico , Lesiones Precancerosas/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Masculino , Detección Precoz del Cáncer/métodos , Femenino , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Anciano , Epigenoma , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , Secuenciación Completa del Genoma/métodos , Microambiente Tumoral/genética
15.
Drug Discov Today ; 29(6): 104018, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723763

RESUMEN

Text summarization is crucial in scientific research, drug discovery and development, regulatory review, and more. This task demands domain expertise, language proficiency, semantic prowess, and conceptual skill. The recent advent of large language models (LLMs), such as ChatGPT, offers unprecedented opportunities to automate this process. We compared ChatGPT-generated summaries with those produced by human experts using FDA drug labeling documents. The labeling contains summaries of key labeling sections, making them an ideal human benchmark to evaluate ChatGPT's summarization capabilities. Analyzing >14000 summaries, we observed that ChatGPT-generated summaries closely resembled those generated by human experts. Importantly, ChatGPT exhibited even greater similarity when summarizing drug safety information. These findings highlight ChatGPT's potential to accelerate work in critical areas, including drug safety.


Asunto(s)
Etiquetado de Medicamentos , United States Food and Drug Administration , Humanos , Estados Unidos , Procesamiento de Lenguaje Natural , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
16.
Neurol Ther ; 13(3): 727-737, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38619804

RESUMEN

INTRODUCTION: Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). METHODS: Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. RESULTS: Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99-1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97-1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95-1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91-1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. CONCLUSIONS: This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

17.
Surg Endosc ; 38(6): 3195-3203, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38632118

RESUMEN

BACKGROUND: We aimed to study the impact of operative time on textbook outcome (TO), especially postoperative complications and length of postoperative stay in minimally invasive esophagectomy. METHODS: Patients undergoing esophagectomy for curative intent within a prospectively maintained database from 2016 to 2022 were retrieved. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with medical teams random effects. A restricted cubic spline (RCS) plotting was used to characterize correlation between operative time and the odds for achieving TO. RESULTS: Data of 2210 patients were examined. Median operative time was 270 mins (interquartile range, 233-313) for all cases. Overall, 902 patients (40.8%) achieved TO. Among non-TO patients, 226 patients (10.2%) had a major complication (grade ≥ III), 433 patients (19.6%) stayed postoperatively longer than 14 days. Multivariable analysis revealed operative time was associated with higher odds of major complications (odds ratio 1.005, P < 0.001) and prolonged postoperative stay (≥ 14 days) (odds ratio 1.003, P = 0.006). The relationship between operative time and TO exhibited an inverse-U shape, with 298 mins identified as the tipping point for the highest odds of achieving TO. CONCLUSIONS: Longer operative time displayed an adverse influence on postoperative morbidity and increased lengths of postoperative stay. In the present study, the TO displayed an inverse U-shaped correlation with operative time, with a significant peak at 298 mins. Potential factors contributing to prolonged operative time may potentiate targets for quality metrics and risk-adjustment process.


Asunto(s)
Esofagectomía , Hospitales de Alto Volumen , Tiempo de Internación , Tempo Operativo , Complicaciones Posoperatorias , Humanos , Esofagectomía/métodos , Esofagectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano , Tiempo de Internación/estadística & datos numéricos , Hospitales de Alto Volumen/estadística & datos numéricos , Neoplasias Esofágicas/cirugía , Resultado del Tratamiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Estudios Retrospectivos , Ajuste de Riesgo/métodos , Laparoscopía/estadística & datos numéricos , Laparoscopía/métodos , Laparoscopía/efectos adversos
18.
Comput Biol Med ; 175: 108487, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653064

RESUMEN

Drug repurposing is promising in multiple scenarios, such as emerging viral outbreak controls and cost reductions of drug discovery. Traditional graph-based drug repurposing methods are limited to fast, large-scale virtual screens, as they constrain the counts for drugs and targets and fail to predict novel viruses or drugs. Moreover, though deep learning has been proposed for drug repurposing, only a few methods have been used, including a group of pre-trained deep learning models for embedding generation and transfer learning. Hence, we propose DeepSeq2Drug to tackle the shortcomings of previous methods. We leverage multi-modal embeddings and an ensemble strategy to complement the numbers of drugs and viruses and to guarantee the novel prediction. This framework (including the expanded version) involves four modal types: six NLP models, four CV models, four graph models, and two sequence models. In detail, we first make a pipeline and calculate the predictive performance of each pair of viral and drug embeddings. Then, we select the best embedding pairs and apply an ensemble strategy to conduct anti-viral drug repurposing. To validate the effect of the proposed ensemble model, a monkeypox virus (MPV) case study is conducted to reflect the potential predictive capability. This framework could be a benchmark method for further pre-trained deep learning optimization and anti-viral drug repurposing tasks. We also build software further to make the proposed model easier to reuse. The code and software are freely available at http://deepseq2drug.cs.cityu.edu.hk.


Asunto(s)
Antivirales , Aprendizaje Profundo , Reposicionamiento de Medicamentos , Reposicionamiento de Medicamentos/métodos , Antivirales/farmacología , Antivirales/uso terapéutico , Humanos , Programas Informáticos , Benchmarking
19.
J Refract Surg ; 40(4): e239-e244, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38593260

RESUMEN

PURPOSE: To explore changes in corneal epithelial thickness (CET) after femtosecond laser-assisted laser in situ keratomileusis in patients with high astigmatism. METHODS: CET was measured at every intersection of the concentric circles and specific axes using AngioVue optical coherence tomography (Angio-OCT) preoperatively and 1 month postoperatively. The average thickness of corneal central, paracentral, and peripheral regions was the mean of the points within the central 2, 2 to 5, and 5 to 7 mm areas, respectively. Correlation analysis was performed to investigate the association between CET along different axes and other preoperative and postoperative parameters. RESULTS: Forty-two eyes of 28 patients were included. CET along the astigmatic (K1) and perpendicular (K2) axes in the central and paracentral areas increased (P < .001), whereas that along the K2 axis decreased in the peripheral area 1 month postoperatively (P = .001). The amount of CET change in the peripheral area between the K1 and K2 axes was significantly different (P < .001). In the central area, the change in CET along the K2 axis was positively correlated with ablation depth (r = 0.315, P = .042) and negatively with refractive power after surgery (r = -0.347, P = .024). In the peripheral area, the changes in CET along both K1 and K2 axes were negatively correlated with ablation depth (r = -0.431, P = .004; r = -0.387, P = .011, respectively). CONCLUSIONS: Epithelial modeling differed between the different astigmatism axes after refractive surgery. The compensatory response of the corneal epithelium is more pronounced along the steeper axis. [J Refract Surg. 2024;40(4):e239-e244.].


Asunto(s)
Astigmatismo , Queratomileusis por Láser In Situ , Miopía , Humanos , Queratomileusis por Láser In Situ/métodos , Agudeza Visual , Astigmatismo/cirugía , Miopía/cirugía , Estudios Prospectivos , Rayos Láser , Láseres de Excímeros/uso terapéutico
20.
Nat Commun ; 15(1): 3246, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622137

RESUMEN

Simultaneously quantifying mitochondrial Cu+ and Cu2+ levels is crucial for evaluating the molecular mechanisms of copper accumulation-involved pathological processes. Here, a series of molecules containing various diacetylene derivatives as Raman reporters are designed and synthesized, and the alkyne-tagged SERS probe is created for determination Cu+ and Cu2+ with high selectivity and sensitivity. The developed SERS probe generates well-separated distinguishable Raman fingerprint peaks with built-in corrections in the cellular silent region, resulting in accurate quantification of Cu+ and Cu2+. The present probe demonstrates high tempo-spatial resolution for real-time imaging and simultaneously quantifying mitochondrial Cu+ and Cu2+ with long-term stability benefiting from the probe assembly with designed Au-C≡C groups. Using this powerful tool, it is found that mitochondrial Cu+ and Cu2+ increase during ischemia are associated with breakdown of proteins containing copper as well as conversion of Cu+ and Cu2+. Meanwhile, we observe that parts of Cu+ and Cu2+ are transported out of neurons by ATPase. More importantly, cuproptosis in neurons is found including the oxidative stress process caused by the conversion of Cu+ to Cu2+, which dominates at the early stage (<9 h), and subsequent proteotoxic stress. Both oxidative and proteotoxic stresses contribute to neuronal death.


Asunto(s)
Alquinos , Cobre , Espectrometría Raman/métodos , Oro , Transporte Biológico
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