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1.
PLoS One ; 19(5): e0300924, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768105

RESUMO

The identification research of hydrogenation catalyst information has always been one of the most important businesses in the chemical industry. In order to aid researchers in efficiently screening high-performance catalyst carriers and tackle the pressing challenge at hand, it is imperative to find a solution for the intelligent recognition of hydrogenation catalyst images. To address the issue of low recognition accuracy caused by adhesion and stacking of hydrogenation catalysts, An image recognition algorithm of hydrogenation catalyst based on FPNC Net was proposed in this paper. In the present study, Resnet50 backbone network was used to extract the features, and spatially-separable convolution kernel was used to extract the multi-scale features of catalyst fringe. In addition, to effectively segment the adhesive regions of stripes, FPN (Feature Pyramid Network) is added to the backbone network for deep and shallow feature fusion. Introducing an attention module to adaptively adjust weights can effectively highlight the target features of the catalyst. The experimental results showed that the FPNC Net model achieved an accuracy of 94.2% and an AP value improvement of 19.37% compared to the original CenterNet model. The improved model demonstrates a significant enhancement in detection accuracy, indicating a high capability for detecting hydrogenation catalyst targets.


Assuntos
Algoritmos , Aprendizado Profundo , Catálise , Hidrogenação , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
2.
Heliyon ; 10(9): e29899, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699020

RESUMO

While the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) has seen some improvement, the majority of NSCLC patients fail to respond to immunotherapy with immune checkpoint inhibitors (ICIs). It is critical to identify effective biomarkers that can enhance the efficacy of immunotherapy. The clinical data in the current study were collected from NSCLC patients treated with ICIs, and two groups were classified according to treatment effect: good group with consistent efficacy, poor group with only progressiveness. Differences in intestinal microbiota between the two groups were analyzed using 16s rRNA sequencing. Beta diversity analysis indicated differences between the two groups that were available for differentiation. Comparison of the number of common or unique operational taxonomic units (OTUs) among different groups suggested that there were 53 unique OTUs in the good group and 51 unique OTUs in the poor group. At the phylum level, there was a difference between the two groups for several bacterial groups with the highest abundance values, among which Firmicutes, Actinobacteria and Fusobacteria were more abundant in the good group. Members of the genera Bifidobacterium and Lactobacillus were abundant in the good group, while the abundance of Bacteroides was low. Biomarkers in the poor group included Bacteroides, Bacteroidetes, Bacteroidia, Bacteroidales, Bacteroidaceae and Veillonellaceae. The intestinal microbiota composition affected the immunotherapy process for NSCLC, which might offer more rational instructions for the clinical application of ICIs in NSCLC patients.

3.
Carbohydr Polym ; 337: 122142, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710551

RESUMO

The growth of cyclodextrin inclusion complexes (ICs) on oil/water interfaces represents a beautiful example of spontaneous pattern formation in nature. How the supramolecules evolve remains a challenge because surface confinement can frustrate microcrystal growth and give rise to unusual phase transitions. Here we investigate the self-assembly of ICs on droplet surfaces using microfluidics, which allows directly visualizing packing, wetting and ordering of the microcrystals anchored on the surface. The oil guests of distinct molecular structures can direct the assembly of the ICs and largely affect anchoring dynamics of the ICs microcrystals, leading to a range of behaviors including orientating, slipping, buckling, jamming, or merging. We discuss the behaviors observed in terms of the flexibility of the building blocks, which offers a new degree of freedom through which to tailor their properties and gives rise to a striking feature of anchoring patterns that have no counterpart in normal colloidal crystals.

4.
Cell Death Discov ; 10(1): 215, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702323

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

5.
Heliyon ; 10(9): e29904, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707440

RESUMO

The role of human cell division cycle 73 (CDC73) in human cancers has sparked controversy; however, its significance in oesophageal cancer remains elusive. This study aimed to elucidate CDC73 expression and its biological implications in human oesophageal cancer. Our findings unveiled a notable upregulation of CDC73 in both oesophageal cancer cell lines and tissues. Importantly, elevated CDC73 levels in patients with oesophageal cancer correlated with an unfavourable prognosis. Functional investigations revealed that CDC73 knockdown effectively curtailed the proliferation and growth of oesophageal cancer cells both in vitro and in vivo. Mechanistically, RRP15 emerged as a potential downstream target of CDC73 through a screening process involving identification of the top co-expressed genes, subsequent knockdown experiments, and observation of significant inhibition of cell proliferation, with RRP15 showing the most pronounced effect. This finding was further supported by the positive correlation observed between CDC73 and RRP15 in ESCA samples analysed using the ENCORI Pan-Cancer Analysis Platform. Notably, depletion of RRP15 in CDC73-overexpressing cells led to a shift from augmented to diminished tumour growth. Collectively, our findings underscore the pivotal role of CDC73 in oesophageal cancer through the modulation of RRP15 expression, suggesting CDC73 as a potential therapeutic target for treating oesophageal cancer.

6.
Phytother Res ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761036

RESUMO

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

7.
EClinicalMedicine ; 72: 102622, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745965

RESUMO

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38581312

RESUMO

Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38597996

RESUMO

We have previously identified a latent interaction mechanism between non-small cell lung cancer cells (NSCLCC) and their associated macrophages (TAM) mediated by mutual paracrine activation of the HMGB1/RAGE/NF-κB signaling. Activation of this mechanism results in TAM stimulation and PD-L1 upregulation in the NSCLCC. In the present work, we found that free DOX at a low concentration that does not cause DNA damage could activate the HMGB1/RAGE/NF-κB/PD-L1 pathway byinducing oxidative stress. It was thus proposed that a combination of low-dose DOX and a PD-L1 blocker delivered in the NSCLC tumor would achieve synergistic TAM stimulation and thereby synergetic anti-tumor potency. To prove this idea, DOX and BMS-202 (a PD-L1 blocker) were loaded to black phosphorus (BP) nanoparticles after dosage titration to yield the BMS-202/DOX@BP composites that rapidly disintegrated and released drug cargo upon mild photothermal heating at 40 °C. In vitro experiments then demonstrated that low-dose DOX and BMS-202 delivered via BMS-202/DOX@BP under mild photothermia displayed enhanced tumor cell toxicity with a potent synergism only in the presence of TAM. This enhanced synergism was due to an anti-tumor M1-like TAM phenotype that was synergistically induced by low dose DOX plus BMS-202 only in the presence of the tumor cells, indicating the damaged tumor cells to be the cardinal contributor to the M1-like TAM stimulation. In vivo, BMS-202/DOX@BP under mild photothermia exhibited targeted delivery to NSCLC graft tumors in mice and synergistic anti-tumor efficacy of delivered DOX and BMS-202. In conclusion, low-dose DOX in combination with a PD-L1 blocker is an effective strategy to turn TAM against their host tumor cells exploiting the HMGB1/RAGE/NF-κB/PD-L1 pathway. The synergetic actions involved highlight the value of TAM and the significance of modulating tumor cell-TAM cross-talk in tumor therapy. Photothermia-responsive BP provides an efficient platform to translate this strategy into targeted, efficacious tumor therapy.

10.
PLoS One ; 19(4): e0295986, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635545

RESUMO

INTRODUCTION: Although the association between nonalcoholic fatty liver disease (NAFLD) and vitamin C has been well studied, the effects of dietary potassium intake on this relationship are still unclear. Thus, this study aimed to determine the effects of dietary potassium intake on the association between vitamin C and NAFLD. METHODS: We performed a cross-sectional learn about with 9443 contributors the usage of 2007-2018 NHANES data. Multiple logistic regression evaluation has been utilized to check out the affiliation of dietary vitamin C intake with NAFLD and advanced hepatic fibrosis (AHF). Subsequently, we plotted a smoothed match curve to visualize the association. Especially, the analysis of AHF was conducted among the NAFLD population. In addition, stratified evaluation used to be developed primarily based on demographic variables to verify the steadiness of the results. Effect amendment by way of dietary potassium intake used to be assessed via interplay checks between vitamin C and NAFLD in the multivariable linear regression. RESULTS: In this cross-sectional study, we found that vitamin C was negatively related to NAFLD and AHF. The relationship between vitamin C and NAFLD was different in the low, middle and high potassium intake groups. Furthermore, potassium intake significantly modified the negative relationship between vitamin C and NAFLD in most of the models. CONCLUSION: Our research showed that potassium and vitamin C have an interactive effect in reducing NAFLD, which may have great importance for clinical medication.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Estados Unidos/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Ácido Ascórbico , Estudos Transversais , Inquéritos Nutricionais , Potássio , Potássio na Dieta , Vitaminas , Ingestão de Alimentos
11.
Food Chem Toxicol ; 188: 114665, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641045

RESUMO

Amanita phalloides is one of the deadliest mushrooms worldwide, causing most fatal cases of mushroom poisoning. Among the poisonous substances of Amanita phalloides, amanitins are the most lethal toxins to humans. Currently, there are no specific antidotes available for managing amanitin poisoning and treatments are lack of efficacy. Amanitin mainly causes severe injuries to specific organs, such as the liver, stomach, and kidney, whereas the lung, heart, and brain are hardly affected. However, the molecular mechanism of this phenomenon remains not understood. To explore the possible mechanism of organ specificity of amanitin-induced toxicity, eight human cell lines derived from different organs were exposed to α, ß, and γ-amanitin at concentrations ranging from 0.3 to 100 µM. We found that the cytotoxicity of amanitin differs greatly in various cell lines, among which liver-derived HepG2, stomach-derived BGC-823, and kidney-derived HEK-293 cells are most sensitive. Further mechanistic study revealed that the variable cytotoxicity is mainly dependent on the different expression levels of the organic anion transporting polypeptide 1B3 (OATP1B3), which facilitates the internalization of amanitin into cells. Besides, knockdown of OATP1B3 in HepG2 cells prevented α-amanitin-induced cytotoxicity. These results indicated that OATP1B3 may be a crucial therapeutic target against amanitin-induced organ failure.


Assuntos
Amanitinas , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto , Humanos , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Amanitinas/toxicidade , Células HEK293 , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Alfa-Amanitina/toxicidade , Células Hep G2
12.
medRxiv ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38633789

RESUMO

Introduction: Serial functional status assessments are critical to heart failure (HF) management but are often described narratively in documentation, limiting their use in quality improvement or patient selection for clinical trials. We developed and validated a deep learning-based natural language processing (NLP) strategy to extract functional status assessments from unstructured clinical notes. Methods: We identified 26,577 HF patients across outpatient services at Yale New Haven Hospital (YNHH), Greenwich Hospital (GH), and Northeast Medical Group (NMG) (mean age 76.1 years; 52.0% women). We used expert annotated notes from YNHH for model development/internal testing and from GH and NMG for external validation. The primary outcomes were NLP models to detect (a) explicit New York Heart Association (NYHA) classification, (b) HF symptoms during activity or rest, and (c) functional status assessment frequency. Results: Among 3,000 expert-annotated notes, 13.6% mentioned NYHA class, and 26.5% described HF symptoms. The model to detect NYHA classes achieved a class-weighted AUROC of 0.99 (95% CI: 0.98-1.00) at YNHH, 0.98 (0.96-1.00) at NMG, and 0.98 (0.92-1.00) at GH. The activity-related HF symptom model achieved an AUROC of 0.94 (0.89-0.98) at YNHH, 0.94 (0.91-0.97) at NMG, and 0.95 (0.92-0.99) at GH. Deploying the NYHA model among 166,655 unannotated notes from YNHH identified 21,528 (12.9%) with NYHA mentions and 17,642 encounters (10.5%) classifiable into functional status groups based on activity-related symptoms. Conclusions: We developed and validated an NLP approach to extract NYHA classification and activity-related HF symptoms from clinical notes, enhancing the ability to track optimal care and identify trial-eligible patients.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38657567

RESUMO

OBJECTIVES: Generative large language models (LLMs) are a subset of transformers-based neural network architecture models. LLMs have successfully leveraged a combination of an increased number of parameters, improvements in computational efficiency, and large pre-training datasets to perform a wide spectrum of natural language processing (NLP) tasks. Using a few examples (few-shot) or no examples (zero-shot) for prompt-tuning has enabled LLMs to achieve state-of-the-art performance in a broad range of NLP applications. This article by the American Medical Informatics Association (AMIA) NLP Working Group characterizes the opportunities, challenges, and best practices for our community to leverage and advance the integration of LLMs in downstream NLP applications effectively. This can be accomplished through a variety of approaches, including augmented prompting, instruction prompt tuning, and reinforcement learning from human feedback (RLHF). TARGET AUDIENCE: Our focus is on making LLMs accessible to the broader biomedical informatics community, including clinicians and researchers who may be unfamiliar with NLP. Additionally, NLP practitioners may gain insight from the described best practices. SCOPE: We focus on 3 broad categories of NLP tasks, namely natural language understanding, natural language inferencing, and natural language generation. We review the emerging trends in prompt tuning, instruction fine-tuning, and evaluation metrics used for LLMs while drawing attention to several issues that impact biomedical NLP applications, including falsehoods in generated text (confabulation/hallucinations), toxicity, and dataset contamination leading to overfitting. We also review potential approaches to address some of these current challenges in LLMs, such as chain of thought prompting, and the phenomena of emergent capabilities observed in LLMs that can be leveraged to address complex NLP challenge in biomedical applications.

14.
Adv Mater ; : e2313721, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669677

RESUMO

Germanium-based monochalcogenides (i.e., GeS and GeSe) with desirable properties are promising candidates for the development of next-generation optoelectronic devices. However, they are still stuck with challenges, such as relatively fixed electronic band structure, unconfigurable optoelectronic characteristics, and difficulty in achieving free-standing growth. Herein, it is demonstrated that two-dimensional (2D) free-standing GeS1-xSex (0 ≤ x ≤ 1) nanoplates can be grown by low-pressure rapid physical vapor deposition (LPRPVD), fulfilling a continuously composition-tunable optical bandgap and electronic band structure. By leveraging the synergistic effect of composition-dependent modulation and free-standing growth, GeS1-xSex-based optoelectronic devices exhibit significantly configurable hole mobility from 6.22 × 10-4 to 1.24 cm2V-1s⁻1 and tunable responsivity from 8.6 to 311 A W-1 (635 nm), as x varies from 0 to 1. Furthermore, the polarimetric sensitivity can be tailored from 4.3 (GeS0.29Se0.71) to 1.8 (GeSe) benefiting from alloy engineering. Finally, the tailored imaging capability is also demonstrated to show the application potential of GeS1-xSex alloy nanoplates. This work broadens the functionality of conventional binary materials and motivates the development of tailored polarimetric optoelectronic devices.

15.
Sci Rep ; 14(1): 8693, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622164

RESUMO

Non-pharmaceutical interventions (NPI) have great potential to improve cognitive function but limited investigation to discover NPI repurposing for Alzheimer's Disease (AD). This is the first study to develop an innovative framework to extract and represent NPI information from biomedical literature in a knowledge graph (KG), and train link prediction models to repurpose novel NPIs for AD prevention. We constructed a comprehensive KG, called ADInt, by extracting NPI information from biomedical literature. We used the previously-created SuppKG and NPI lexicon to identify NPI entities. Four KG embedding models (i.e., TransE, RotatE, DistMult and ComplEX) and two novel graph convolutional network models (i.e., R-GCN and CompGCN) were trained and compared to learn the representation of ADInt. Models were evaluated and compared on two test sets (time slice and clinical trial ground truth) and the best performing model was used to predict novel NPIs for AD. Discovery patterns were applied to generate mechanistic pathways for high scoring candidates. The ADInt has 162,212 nodes and 1,017,284 edges. R-GCN performed best in time slice (MR = 5.2054, Hits@10 = 0.8496) and clinical trial ground truth (MR = 3.4996, Hits@10 = 0.9192) test sets. After evaluation by domain experts, 10 novel dietary supplements and 10 complementary and integrative health were proposed from the score table calculated by R-GCN. Among proposed novel NPIs, we found plausible mechanistic pathways for photodynamic therapy and Choerospondias axillaris to prevent AD, and validated psychotherapy and manual therapy techniques using real-world data analysis. The proposed framework shows potential for discovering new NPIs for AD prevention and understanding their mechanistic pathways.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Aprendizagem
16.
Nanomaterials (Basel) ; 14(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38668184

RESUMO

It is usually difficult to realize high mobility together with a low threshold voltage and good stability for amorphous oxide thin-film transistors (TFTs). In addition, a low fabrication temperature is preferred in terms of enhancing compatibility with the back end of line of the device. In this study, α-IGZO TFTs were prepared by high-power impulse magnetron sputtering (HiPIMS) at room temperature. The channel was prepared under a two-step deposition pressure process to modulate its electrical properties. X-ray photoelectron spectra revealed that the front-channel has a lower Ga content and a higher oxygen vacancy concentration than the back-channel. This process has the advantage of balancing high mobility and a low threshold voltage of the TFT when compared with a conventional homogeneous channel. It also has a simpler fabrication process than that of a dual active layer comprising heterogeneous materials. The HiPIMS process has the advantage of being a low temperature process for oxide TFTs.

17.
Int J Qual Health Care ; 36(2)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38619120

RESUMO

BACKGROUND: Falls were among the most common adverse nursing events. The incidence of falls in patients with neuropsychiatric disorders was high, and the occurrence of falls not only caused physical and psychological harm to patients but also led to medical disputes. Therefore, interventions for falls prevention were essential, but evaluations of the intervention process were lacking. METHODS: In this study, a process management program to prevent falls based on the "structure-process-outcome" quality evaluation model was designed and applied to the clinical practice of falls prevention in hospitalized patients with neuropsychiatric disorders. The process quality evaluation checklist to prevent falls was used to supervise the implementation effect of intervention measures to prevent falls, identify the problems in the intervention measures, and make continuous improvements, to reduce the incidence of falls in such hospitalized patients as the final index. RESULTS: The incidence of inpatient falls decreased from 0.199‰ (0.199 per 1000 patient-days) to 0.101‰ (0.101 per 1000 patient-days) before and after the implementation of the process management program for 12 months, 24 months, and 36 months, respectively, and the difference was statistically significant (P < .05). The probability of falls was reduced by 49% after 36 months of monitoring. Furthermore, the proportion of patients at high risk of falls exhibited a downward trend. CONCLUSION: This quality improvement program was feasible and effective at reducing falls in hospitalized patients with neuropsychiatric disorders. Therefore, attention should be given to monitoring process quality in the management of falls.


Assuntos
Acidentes por Quedas , Transtornos Mentais , Melhoria de Qualidade , Humanos , Acidentes por Quedas/prevenção & controle , Melhoria de Qualidade/organização & administração , Transtornos Mentais/terapia , Feminino , Hospitalização , Masculino , Incidência , Pacientes Internados , Idoso , Pessoa de Meia-Idade , Lista de Checagem
18.
J Healthc Inform Res ; 8(2): 206-224, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38681754

RESUMO

Biomedical relation extraction (RE) is critical in constructing high-quality knowledge graphs and databases as well as supporting many downstream text mining applications. This paper explores prompt tuning on biomedical RE and its few-shot scenarios, aiming to propose a simple yet effective model for this specific task. Prompt tuning reformulates natural language processing (NLP) downstream tasks into masked language problems by embedding specific text prompts into the original input, facilitating the adaption of pre-trained language models (PLMs) to better address these tasks. This study presents a customized prompt tuning model designed explicitly for biomedical RE, including its applicability in few-shot learning contexts. The model's performance was rigorously assessed using the chemical-protein relation (CHEMPROT) dataset from BioCreative VI and the drug-drug interaction (DDI) dataset from SemEval-2013, showcasing its superior performance over conventional fine-tuned PLMs across both datasets, encompassing few-shot scenarios. This observation underscores the effectiveness of prompt tuning in enhancing the capabilities of conventional PLMs, though the extent of enhancement may vary by specific model. Additionally, the model demonstrated a harmonious balance between simplicity and efficiency, matching state-of-the-art performance without needing external knowledge or extra computational resources. The pivotal contribution of our study is the development of a suitably designed prompt tuning model, highlighting prompt tuning's effectiveness in biomedical RE. It offers a robust, efficient approach to the field's challenges and represents a significant advancement in extracting complex relations from biomedical texts. Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-024-00162-9.

19.
J Healthc Inform Res ; 8(2): 438-461, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38681753

RESUMO

Purpose: Phenotyping is critical for informing rare disease diagnosis and treatment, but disease phenotypes are often embedded in unstructured text. While natural language processing (NLP) can automate extraction, a major bottleneck is developing annotated corpora. Recently, prompt learning with large language models (LLMs) has been shown to lead to generalizable results without any (zero-shot) or few annotated samples (few-shot), but none have explored this for rare diseases. Our work is the first to study prompt learning for identifying and extracting rare disease phenotypes in the zero- and few-shot settings. Methods: We compared the performance of prompt learning with ChatGPT and fine-tuning with BioClinicalBERT. We engineered novel prompts for ChatGPT to identify and extract rare diseases and their phenotypes (e.g., diseases, symptoms, and signs), established a benchmark for evaluating its performance, and conducted an in-depth error analysis. Results: Overall, fine-tuning BioClinicalBERT resulted in higher performance (F1 of 0.689) than ChatGPT (F1 of 0.472 and 0.610 in the zero- and few-shot settings, respectively). However, ChatGPT achieved higher accuracy for rare diseases and signs in the one-shot setting (F1 of 0.778 and 0.725). Conversational, sentence-based prompts generally achieved higher accuracy than structured lists. Conclusion: Prompt learning using ChatGPT has the potential to match or outperform fine-tuning BioClinicalBERT at extracting rare diseases and signs with just one annotated sample. Given its accessibility, ChatGPT could be leveraged to extract these entities without relying on a large, annotated corpus. While LLMs can support rare disease phenotyping, researchers should critically evaluate model outputs to ensure phenotyping accuracy.

20.
Biosens Bioelectron ; 257: 116300, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657378

RESUMO

Developing simple, inexpensive, fast, sensitive, and specific probes for antibiotic-resistant bacteria is crucial for the management of urinary tract infections (UTIs). We here propose a paper-based sensor for the rapid detection of ß-lactamase-producing bacteria in the urine samples of UTI patients. By conjugating a strongly electronegative group -N+(CH3)3 with the core structures of cephalosporin and carbapenem antibiotics, two visual probes were achieved to respectively target the extended-spectrum/AmpC ß-lactamases (ESBL/AmpC) and carbapenemase, the two most prevalent factors causing antibiotic resistance. By integrating these probes into a portable paper sensor, we confirmed 10 and 8 cases out of 30 clinical urine samples as ESBL/AmpC- and carbapenemase-positive, respectively, demonstrating 100% clinical sensitivity and specificity. This paper sensor can be easily conducted on-site, without resorting to bacterial culture, providing a solution to the challenge of rapid detection of ß-lactamase-producing bacteria, particularly in resource-limited settings.


Assuntos
Técnicas Biossensoriais , Papel , Infecções Urinárias , beta-Lactamases , beta-Lactamases/metabolismo , beta-Lactamases/química , Humanos , Infecções Urinárias/microbiologia , Infecções Urinárias/diagnóstico , Técnicas Biossensoriais/métodos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Proteínas de Bactérias , Bactérias/isolamento & purificação , Bactérias/enzimologia , Cefalosporinas/química , Carbapenêmicos/farmacologia
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