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BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.
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Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Instabilidade de Microssatélites , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Idoso , Adulto , Reparo de Erro de Pareamento de DNA , Quimioterapia Adjuvante/métodos , SeguimentosRESUMO
Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation.
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Testes de Irritação da Pele , Pele , Humanos , Pele/efeitos dos fármacos , Testes de Irritação da Pele/métodos , Irritantes/toxicidade , Animais , Alternativas aos Testes com Animais/métodos , Engenharia Tecidual/métodos , Modelos BiológicosRESUMO
Antimicrobial peptides (AMPs) have attracted considerable interest in the past decade due to their advantages for tackling antibiotic resistance. They exhibit potential antimicrobial activity through unique cell membrane destruction mechanism based on their net charge, hydrophobic properties, and α-helix. In this work, a series of HJH peptides was rationally designed and synthesized. The antimicrobial activity and cytotoxicity assays indicated that HJH-5 and HJH-6 containing hydrophobic residues and helices displayed prominent antimicrobial activity and mild cytotoxicity, respectively. These peptides may be developed for combatting microbial infections.
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Anti-Infecciosos , Peptídeos Catiônicos Antimicrobianos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Antimicrobianos , Membrana Celular , Resistência Microbiana a Medicamentos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
BACKGROUND: Discharge medical notes written by physicians contain important information about the health condition of patients. Many deep learning algorithms have been successfully applied to extract important information from unstructured medical notes data that can entail subsequent actionable results in the medical domain. This study aims to explore the model performance of various deep learning algorithms in text classification tasks on medical notes with respect to different disease class imbalance scenarios. METHODS: In this study, we employed seven artificial intelligence models, a CNN (Convolutional Neural Network), a Transformer encoder, a pretrained BERT (Bidirectional Encoder Representations from Transformers), and four typical sequence neural networks models, namely, RNN (Recurrent Neural Network), GRU (Gated Recurrent Unit), LSTM (Long Short-Term Memory), and Bi-LSTM (Bi-directional Long Short-Term Memory) to classify the presence or absence of 16 disease conditions from patients' discharge summary notes. We analyzed this question as a composition of 16 binary separate classification problems. The model performance of the seven models on each of the 16 datasets with various levels of imbalance between classes were compared in terms of AUC-ROC (Area Under the Curve of the Receiver Operating Characteristic), AUC-PR (Area Under the Curve of Precision and Recall), F1 Score, and Balanced Accuracy as well as the training time. The model performances were also compared in combination with different word embedding approaches (GloVe, BioWordVec, and no pre-trained word embeddings). RESULTS: The analyses of these 16 binary classification problems showed that the Transformer encoder model performs the best in nearly all scenarios. In addition, when the disease prevalence is close to or greater than 50%, the Convolutional Neural Network model achieved a comparable performance to the Transformer encoder, and its training time was 17.6% shorter than the second fastest model, 91.3% shorter than the Transformer encoder, and 94.7% shorter than the pre-trained BERT-Base model. The BioWordVec embeddings slightly improved the performance of the Bi-LSTM model in most disease prevalence scenarios, while the CNN model performed better without pre-trained word embeddings. In addition, the training time was significantly reduced with the GloVe embeddings for all models. CONCLUSIONS: For classification tasks on medical notes, Transformer encoders are the best choice if the computation resource is not an issue. Otherwise, when the classes are relatively balanced, CNNs are a leading candidate because of their competitive performance and computational efficiency.
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Aprendizado Profundo , Algoritmos , Inteligência Artificial , Humanos , Redes Neurais de Computação , Curva ROCRESUMO
Cyclic arginine-glycine-aspartic (RGD) peptides that specifically bind to integrin ανß3 have been developed for drug delivery, tracers, and imaging for tumor diagnosis and treatment. Herein, a series of polycyclic RGD peptides containing dual, tri, and tetra rings were designed and synthesized through sortase A-mediated ligation. An in vitro test on cell adhesion inhibition indicated that the RGD peptide containing tricylic structure exhibited outstanding potency and selectivity for ανß3 integrin.
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Integrina alfaVbeta3 , Integrina beta3 , Aminoaciltransferases , Proteínas de Bactérias , Ciclização , Cisteína Endopeptidases , Integrina alfaVbeta3/metabolismo , Integrina beta3/metabolismo , Oligopeptídeos/químicaRESUMO
CsPbX3(X = Cl, Br, I) semiconductor nanocrystals (NCs) have excellent optical and photoelectric properties, and are potential core materials for various photoelectric devices. However, the toxicity of Pb and instability have been the key limitations to application of NCs. Herein, using MnBr2and MnBr2·4H2O as manganese sources, heavy Mn-doped CsPbBr3(Mn:CsPbBr3) NCs are synthesized by high-energy ball grinding, which avoids high temperature, a large number of polar solvents and atmosphere protection required in traditional liquid phase methods. However, when MnBr2·4H2O is used as the raw material, infinite solid solution doping can be achieved, and the synthesized Mn:CsPbBr3NCs show smaller particle size, stronger PL intensity and stability. The reason is that presence of crystal water plays a similar role to wet milling in the ball milling process, and can promote the passivation effect of oleylamine (OAm) on nanocrystal defects and the connection between them. In addition, a simple, easy-operating and beneficial to commercial production method for the preparation of Mn:CsPbBr3NCs/EVA flexible films is proposed, which can effectively improve the stability of Mn:CsPbBr3NCs. This study is expected to provide an effective way for the synthesis and stability improvement of CsPbX3NCs doped with different ions.
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Oxygen reduction reaction (ORR) occupies a pivotal position in fuel cell applications, and it is a challenge to obtain highly durable ORR catalysts. Herein, porous cobalt oxide microsphere growing at the surface of on nitrogen-doped graphitized-nano-diamond (CoOx/N-GND) was prepared using hydrothermal and subsequent heat treatment process. Porous cobalt oxide of high specific surface area could expose more surface Co2+that act as active sites than bulk one does. The doping of nitrogen also promotes the catalytic activity. Besides, nano-diamond (ND) ofsp3hybrid structure was used as an electronic conduction carriers of ultrahigh stability to improve the durability of catalytic composite. Prepared CoOx/N-GND shows a satisfactory half-wave potential of 0.82 V (versus RHE), which is close to that of Pt/C (0.85 V), an excellent methanol tolerance and a lower activity loss after 5000 cycles. These merits inspire the application of CoOx/N-GND as the cathode of Zn-air battery and the battery performance was evaluated in this work. In general, this work highlights an innovate approach to design and prepare highly durable catalyst.
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Photocatalytic degradation of pollutants has been proved to be an effective strategy for wastewater treatment. Herein, TiO2 nanoparticles were synthesized on a Ti3C2 matrix by in situ growth, forming Z-scheme TiO2@Ti3C2/Cd0.5Zn0.5S (TO/CZS) multilevel structured nanocomposites via one-step hydrothermal route. The effects of hydrothermal temperature and Cd0.5Zn0.5S content on microstructure and properties of composites were assessed. TO/CZS nanocomposites were probed into phase composition, morphological and optical properties with x-ray diffractometer, infrared radiation, scanning electron microscope and UV-vis reflective spectra. Following the hydrothermal reaction at 160 °C for 12 h, TiO2 nanoparticles of 30 nm in diameter were generated in situ on Ti3C2 lamina and Cd0.5Zn0.5S particles were evenly distributed on the Ti3C2 matrix. The photocatalytic activity of TO/CZS composites were evaluated, which found that degradation rate constant (k = 0.028 min-1) of TO/CZS-40 on Rhodamine B was 5.19 times that of pure TiO2 and 4.48 times that of Cd0.5Zn0.5S. Through anchoring Ti3C2 as an electron transition mediator and combination with TiO2 and Cd0.5Zn0.5S, the new Z-scheme between TiO2 oxidized by Ti3C2 and Cd0.5Zn0.5S establishes a multilevel structure of separating electron-hole pairs. This work demonstrates a valid way to control electrons and hole transfer directions efficiently through designing multilevel semiconductor structural designs.
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MXenes represent an emerging family of two-dimensional materials of transition metal carbides/carbonitrides terminated with functional groups like -O, -OH, and -F on the chemically active surface of MX slabs. As a member of the family, Nb2CTx exhibits superior lithium storage capacity over most of the other MXenes as anode materials in lithium-ion batteries (LIBs). However, an in-depth understanding of the charge storage mechanism is still lacking so far. Here, through combining complementary experiments and density functional theory calculations, we provide insights into the (de)lithiation process. Specifically, Nb2CTx with dominant -O functional groups stores charge as a result of changes in the oxidation states of both transition metals Nb and O, which is supported by Bader charge analysis showing a significant change in the oxidation states of Nb and O upon lithiation. As monitored by ex situ X-ray diffraction, the interlayer spacing of Nb2CTx changes slightly upon lithium ion (de)intercalation, corresponding to a volume change of only 2.3% with a near zero-strain feature. By coupling with a LiFePO4/C cathode, the full cell presents superior rate capability and cycling stability as well. The insights into the charge storage mechanism of Nb2CTx in this work provide useful guidance for the rational design of MXene-based anode materials for high-performance LIBs.
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PURPOSE: We analyzed and compared the imaging characteristics of the vessel wall of the middle cerebral artery (MCA) in symptomatic and asymptomatic patients using a 3.0-T high-resolution magnetic resonance imaging (HR-MRI) protocol, including a 3-dimensional T1-sampling perfection with application-optimized contrasts using different flip angle evolutions sequence. METHODS: Fifty-three patients with atherosclerotic stenosis of the MCA underwent 3.0-T HR-MRI examinations. The characteristics of atherosclerotic plaques in 53 patients (28 symptomatic, 25 asymptomatic) were analyzed, including plaque distribution and signal intensity. Plaque burden (PB), stenosis degree, and the remodeling index were measured and compared between symptomatic and asymptomatic patients. RESULTS: The PB of the symptomatic group was significantly higher than that of the asymptomatic group (P = .006), and moderate-severe stenosis was more common (P = .01). The remodeling index of the symptomatic group was also lower (P = .015) and negative remodeling (NR) was more common (P = .043). Binary logistic regression analysis showed that stenosis degree was a risk factor in symptomatic patients (odds ratio = 135, P = .023). CONCLUSION: There is a trend that some characteristics of plaques and vessels, including the moderate-severe stenosis, larger PB, and NR, were observed more frequently among patients with symptomatic atherosclerotic stenosis of the MCA than among asymptomatic patients.
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Aterosclerose/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Artéria Cerebral Média/diagnóstico por imagem , Constrição Patológica , Estudos de Avaliação como Assunto , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND Bronchial epithelial cells proliferation plays a pivotal role in airway remodeling in children with severe asthma. MicroRNAs (miRNAs) have gained great attention for many diseases, including asthma. The purpose of this study was to explore the mechanisms that underlie miR-744 modulating bronchial epithelial cells proliferation in severe asthma in children. MATERIAL AND METHODS Bronchial epithelial cells were isolated from bronchial biopsies of normal controls and asthmatic subjects. miR-744 and transforming growth factor-ß1 (TGF-ß1) expressions were measured by quantitative reverse transcription PCR (qRT-PCR). Proliferating cell nuclear antigen (PCNA), phosphorylation or total of mothers against decapentaplegic homolog3 (Smad3) and production of Smad anchor for receptor activation (SARA) were measured via Western blot analysis. A link between miR-744 and TGF-ß1 was probed by luciferase activity and RNA immunoprecipitation. Cell proliferation was evaluated using the Cell Proliferation Assay Kit. RESULTS Severe asthma showed a significantly elevated cell proliferation rate and reduced abundance of miR-744, which in turn inhibited cell proliferation of bronchial epithelial cells. In particular, TGF-ß1 might be a candidate target of miR-744, and enrichment of miR-744 lowered the expression of TGF-ß1 at mRNA and protein levels. Indeed, overexpression of miR-744 lowered the proliferation rate of bronchial epithelial cells via driving TGF-ß1. Moreover, addition of miR-744 limited phosphorylation of Smad3 but reversed SARA protein abundance by regulating TGF-ß1. CONCLUSIONS The presence of miR-744 repressed bronchial epithelial cells proliferation through mediating the Smad3 pathway by modulating TGF-ß1, providing a promising therapeutic approach for epithelial function in severe asthma.
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Asma/metabolismo , MicroRNAs/metabolismo , Mucosa Respiratória/metabolismo , Asma/patologia , Brônquios/citologia , Brônquios/metabolismo , Brônquios/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Criança , Células Epiteliais/metabolismo , Feminino , Humanos , Masculino , MicroRNAs/genética , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mucosa Respiratória/patologia , Transdução de Sinais , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/fisiologiaRESUMO
By depositing a graphene layer on the metallic film with subwavelength hole arrays, the tunable extraordinary transmission property based on the metal-dielectrics-graphene (MDG) structure has been investigated in the terahertz (THz) and near-infrared (NIR) regimes. The influences of operation frequency, composed materials, and the Fermi level of the graphene layer have been taken into account. The results show that by varying the Fermi level of the graphene layer, the transmission of the MDG structure can be tuned in a wide range and the modulation depth of the peak value of the transmission can reach more than 50%. But the tunable mechanisms in the THz and NIR regimes are quite different. In the infrared (THz) regime, the graphene behaves like the dielectric (metallic) layer; its dielectric constant decreases (increases) with the increase of Fermi level, resulting in the transmission increasing (decreasing). Compared with the metallic structure, the transmission of the semiconductor structure can also be modulated by using the doping or varying temperature; its peak position can also be changed in a much broader range. The results are very useful to understand the mechanism of the graphene plasmonic devices and to design novel filters, switchers, modulators, and sensors.
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Background: Asthma is a chronic inflammatory disorder with high prevalence in childhood. Airway remodeling, an important structural change of the airways, is resulted from epithelial-mesenchymal transition. Long non-coding RNA non-coding RNA activated by DNA damage (NORAD) has been found to promote epithelial-mesenchymal transition in multiple cancers. This study aimed to analyze the role of NORAD in asthma, mainly focusing on epithelial-mesenchymal transition-mediated airway remodeling, and further explored the NORAD-miRNA-mRNA network. Methods: NORAD expression was analyzed in transforming growth factor-ß1-induced BEAS-2B human bronchial epithelial cells and ovalbumin-challenged asthmatic mice. The influences of NORAD on the epithelial-mesenchymal transition characteristics and Wnt/ß-catenin pathway activation were analyzed in vitro. The interactions between NORAD and miR-410-3p as well as miR-410-3p and regulator of chromosome condensation 2 were detected by dual-luciferase reporter assay and RNA pull-down assay. Rescue experiments using miR-410-3p antagonist and chromosome condensation 2 overexpression were used to confirm the mechanism of NORAD. Additionally, the role and mechanism of NORAD were further evaluated in asthmatic mice. Results: NORAD expression was elevated in both asthmatic models. Knockdown of NORAD impeded spindle-like morphology changes, elevated E-cadherin expression, decreased N-cadherin expression, suppressed cell migration, and inactivated the Wnt/ß-catenin pathway in transforming growth factor-ß1-stimulated BEAS-2B cells. NORAD acted as a sponge of miR-410-3p to regulate chromosome condensation 2 expression. Rescue assays demonstrated that silencing of NORAD ameliorated transforming growth factor-ß1-induced EMT via miR-410-3p/chromosome condensation 2/Wnt/ß-catenin axis. In vivo, knockdown of NORAD led to the reduction of inflammatory cell infiltration and collagen deposition, suppression of IL-4, IL-13, transforming growth factor-ß1 and immunoglobulin E production, decreasing of N-cadherin, chromosome condensation 2, ß-catenin and c-Myc expression, but increasing of E-cadherin and miR-410-3p expression. Conclusions: Silencing of NORAD alleviated epithelial-mesenchymal transition-mediated airway remodeling in asthma via mediating miR-410-3p/chromosome condensation 2/Wnt/ß-catenin pathway.
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Vacuum induction melting is a more energy-efficient process for the preparation of a titanium alloy with good homogeneity and low cost. But the crucial problem for this technology is in developing a crucible refractory with high stability. In the present work, a novel (Ca,Sr,Ba)ZrO3 crucible was prepared by slip casting and its performance in melting NiTi alloy was studied. The results showed that a single solid solution was formed with a homogeneous distribution of metal elements after sintering at 1500 °C. It was found that the total content of oxygen and nitrogen remaining in the TiNi alloy after melting in the (Ca,Sr,Ba)ZrO3 crucible was 0.0173 wt.%, which fulfills the ASTM standard on biomedical TiNi alloys. The good resistance of the (Ca,Sr,Ba)ZrO3 crucible to molten NiTi has a relationship with the sluggish diffusion effect of high-entropy ceramics. This study provides insights into the process of designing highly suitable crucible material for melting a NiTi alloy.
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BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival. METHODS: We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer's disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs. RESULTS: Here, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098). CONCLUSIONS: Based on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.
Alzheimer's disease is the most common type of dementia, affecting millions of people worldwide. In this study, we investigated the effects of two drugs commonly prescribed to people with Alzheimer's disease called Donepezil and Memantine to see whether they had an impact on when people died. We found that the combined use of Donepezil and Memantine significantly increased the probability of a person surviving five years compared to no drug treatment or treatment with Donepezil or Memantine alone. Our results suggest that the lives of many Alzheimer's patients in the USA who are currently on no drug treatment or just Donepezil or Memantine could be extended if they were treated with both drugs simultaneously.
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The misuse and abuse of opioids has become a serious public health threat in the United States. The state of California has been hit particularly hard by the opioid epidemic, with a noticeable increase in opioid-related fatalities and hospitalizations. This brief report paper aims to contribute to the growing literature by conducting a geospatial analysis of opioid dispensing patterns in California in 2021. The primary objective was to identify areas characterized by high-risk opioid dispending patterns and explore possible contributing factors. This retrospective study analyzed data from over 7 million records of opioid and benzodiazepine prescriptions dispensed by outpatient pharmacies in California in 2021. A series of generalized linear regression models was employed to assess the impact of neighborhood characteristics on opioid recipients and high-risk opioid dispensing. The study defined high-risk opioid dispensing behavior as: (1) multiple provider episodes, (2) overlapping opioid prescriptions for seven or more days, (3) overlapping opioid and benzodiazepine prescriptions for seven or more days, and (4) a high standardized dosage of opioid prescriptions per month. The study identified variables associated with high-risk opioid dispensing behaviors, including age, population density, income, and housing-related variables, as well as marital status and family-related variables. The study uncovered that there are noticeable disparities in opioid dispensing among different racial and ethnic groups within California. The findings indicated a correlation of high-risk dispensing indicators with certain demographic and socioeconomic factors. There was a substantial regional variation in opioid dispensing practices, with certain rural areas having higher rates of opioid prescriptions than urban areas.
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INTRODUCTION: Gastric neuroendocrine carcinoma (GNENs), as a highly malignant gastrointestinal tumor, is characterized by easy postoperative metastasis, and its prognosis has always been poor compared to other gastrointestinal tumors. Due to its rarity, there have been few case reports and studies on it. As of now, there is no clear diagnosis and treatment sequence and guidelines. In this report, we present a case of GNENs that underwent first-line treatment after surgery. The patient achieved an excellent prognosis and survival after a combination of chemotherapy resistance and immunotherapy. This report aims to provide valuable reference and guidance for the treatment of GNENs in the future. Therefore, we conducted a literature review on GNENs. PATIENT CONCERNS: A 61-year-old man was admitted to the hospital with complaints of upper abdominal distension and discomfort that had been persistent for 1 month. During the endoscopy examination, a 2.5 cm irregular deep mucosal defect was observed at the center of the gastric angle. The defect appeared covered with dirty moss, had a hard texture, and exhibited a tendency to bleed upon contact. DIAGNOSIS: Biopsy results confirmed the presence of a medium to poorly differentiated adenocarcinoma in the gastric horn. Subsequently, the patient underwent surgery, and the removed specimen was diagnosed as GNENs. INTERVENTION: Postoperative chemotherapy combined with immunotherapy. OUTCOME: The patient in this case achieved a good prognosis and extremely long survival [overall survivalâ >â 3 years+] after receiving first-line treatment, which included chemotherapy, drug resistance and immunotherapy, and is currently in good health condition. The tumor is not sensitive to the standard EP regimen for neuroendocrine carcinoma, but after being replaced with oxaliplatin based regimen combined with immunotherapy, partial response was obtained, indicating a synergistic effect between chemotherapy and immunity. After treatment, it remained stable for a considerable period of time. CONCLUSION: Immunotherapy, as a new mode of cancer treatment can provide new guidance and ideas for the treatment of GNENs.
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Adenocarcinoma , Carcinoma Neuroendócrino , Neoplasias Gástricas , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Adenocarcinoma/patologia , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , ImunoterapiaRESUMO
Suicidal and self-injurious incidents in correctional settings deplete the institutional and healthcare resources, create disorder and stress for staff and other inmates. Traditional statistical analyses provide some guidance, but they can only be applied to structured data that are often difficult to collect and their recommendations are often expensive to act upon. This study aims to extract information from medical and mental health progress notes using AI algorithms to make actionable predictions of suicidal and self-injurious events to improve the efficiency of triage for health care services and prevent suicidal and injurious events from happening at California's Orange County Jails. The results showed that the notes data contain more information with respect to suicidal or injurious behaviors than the structured data available in the EHR database at the Orange County Jails. Using the notes data alone (under-sampled to 50%) in a Transformer Encoder model produced an AUC-ROC of 0.862, a Sensitivity of 0.816, and a Specificity of 0.738. Incorporating the information extracted from the notes data into traditional Machine Learning models as a feature alongside structured data (under-sampled to 50%) yielded better performance in terms of Sensitivity (AUC-ROC: 0.77, Sensitivity: 0.89, Specificity: 0.65). In addition, under-sampling is an effective approach to mitigating the impact of the extremely imbalanced classes.
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Prisões , Ideação Suicida , Humanos , Algoritmos , Aprendizado de Máquina , Bases de Dados FactuaisRESUMO
Ethylicin (ET) was reported to be promising in the control of rice bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo). The detailed mechanism for this process remains unknown. Disclosed here is an in-depth study on the action mode of ET to Xoo. Through plant physiological and biochemical analysis, it was found that ET could inhibit the proliferation of Xoo by increasing the content of defense enzymes and chlorophyll in rice (Oryza sativa ssp. Japonica cv. Nipponbare). Label-free quantitative proteomic analysis showed that ET affected the rice abscisic acid (ABA) signal pathway and made the critical differential calcium-dependent protein kinase 24 (OsCPK24) more active. In addition, the biological function of OsCPK24 as a mediator for rice resistance to Xoo was determined through the anti-Xoo phenotypic test of OsCPK24 transgenic rice and the affinity analysis of the OsCPK24 recombinant protein in vitro and ET. This study revealed the molecular mechanism of ET-induced resistance to Xoo in rice via OsCPK24, which provided a basis for the development of new bactericides based on the OsCPK24 protein.
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Oryza , Xanthomonas , Oryza/metabolismo , Proteômica , Ácido Abscísico/metabolismo , Doenças das Plantas/microbiologiaRESUMO
TiO2/Au/BDD composites with a Z-scheme structure was prepared by orderly depositing gold (Au) and titanium dioxide (TiO2) on the surface of a boron-doped diamond (BDD) film using sputtering and electrophoretic deposition methods. It was found that the introduction of Au between TiO2 and the BDD, not only could reduce their contact resistance, to increase the carrier transport efficiency, but also could improve the surface Hall mobility of the BDD electrode. Meanwhile, the designed Z-scheme structure provided a fast channel for the electrons and holes combination, to promote the effective separation of the electrons and holes produced in TiO2 and the BDD under photoirradiation. The electrochemical characterization elucidated that these modifications of the structure obviously enhanced the electrocatalytic performance of the electrode, which was further verified by the simulated wastewater degradation experiments with reactive brilliant red X-3B. In addition, it was also found that the photoirradiation effectively enhanced the pollution degradation efficiency of the modified electrode, especially for the TiO2/Au/BDD-30 electrode.