Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory.

5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-ß-galactosidase (SA-ß-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

The Mediterranean-dietary approaches to stop hypertension diet intervention for neurodegenerative delay (MIND) diet: a bibliometric analysis.

The MIND diet is a healthy dietary pattern that has some benefits for many health outcomes. Our study aims to conduct a bibliometric analysis of the MIND diet, identifying leading edges and hotspots to provide a reference for future research. The research on the MIND diet was gathered from the Web of Science Core Collection (WOSCC) database. For bibliometric analysis, VOSviewer 1.6.16 and the WOSCC Online Analysis Platform were utilized. In total, this comprehensive investigation encompassed 171 documents in the field of the MIND diet. The publications are globally distributed, with contributions from 953 authors across 362 institutions in 37 countries/regions, and published in 94 journals. The United States leads with 72 publications, and Iran and the People's Republic of China also show notable engagement with 28 and 19 publications, respectively. Rush University stands out with 21 publications, followed by Harvard University and Tehran University of Medical Sciences, demonstrating their substantial contributions to this field. Martha Clare Morris is a key figure with 10 publications, alongside Klodian Dhana and Puja Agarwal, each contributing 9 publications, highlighting their influence in the MIND diet research. The journal "Nutrients" is a major publication venue with 20 related articles, followed by "Frontiers in Nutrition" and "Journal of Nutrition Health Aging," reflecting their crucial roles in advancing knowledge about the MIND diet. The first high-cited publication was published in Alzheimers & Dementia and conducted by Martha Clare Morris, which focuses on the MIND diet's relationship with Alzheimer's disease prevention and cognitive decline and emphasizes the diet's neuroprotective potential, highlighting how even moderate adherence can substantially reduce Alzheimer's risk and slow cognitive decline. In conclusion, this is the first comprehensive bibliometric study that quantitatively and qualitatively analyzed the publications in the field of the MIND diet. The MIND diet may be a promising dietary pattern for dementia. However, the current evidence is restricted and highlights the urgency and necessity of further research to investigate the efficacy of this diet for cognitive function. In addition, the MIND diet may have some benefits for other health outcomes, including CVDs, cancer, and diabetes. The number of studies in the field of the MIND diet is limited. More studies are needed, and will give us more knowledge about the MIND diet to improve human health, especially for dementia.

SNX5-Rab11a protects against cardiac hypertrophy through regulating LRP6 membrane translocation.

BACKGROUNDS: Pathological cardiac hypertrophy is considered one of the independent risk factors for heart failure, with a rather complex pathogenic machinery. Sorting nexins (SNXs), denoting a diverse family of cytoplasmic- and membrane-associated phosphoinositide-binding proteins, act as a pharmacological target against specific cardiovascular diseases including heart failure. Family member SNX5 was reported to play a pivotal role in a variety of biological processes. However, contribution of SNX5 to the development of cardiac hypertrophy, remains unclear. METHODS: Mice underwent transverse aortic constriction (TAC) to induce cardiac hypertrophy and simulate pathological conditions. TAC model was validated using echocardiography and histological staining. Expression of SNX5 was assessed by western blotting. Then, SNX5 was delivered through intravenous administration of an adeno-associated virus serotype 9 carrying cTnT promoter (AAV9-cTnT-SNX5) to achieve SNX5 cardiac-specific overexpression. To assess the impact of SNX5, morphological analysis, echocardiography, histological staining, hypertrophic biomarkers, and cardiomyocyte contraction were evaluated. To unravel potential molecular events associated with SNX5, interactome analysis, fluorescence co-localization, and membrane protein profile were evaluated. RESULTS: Our results revealed significant downregulated protein level of SNX5 in TAC-induced hypertrophic hearts in mice. Interestingly, cardiac-specific overexpression of SNX5 improved cardiac function, with enhanced left ventricular ejection fraction, fraction shortening, as well as reduced cardiac fibrosis. Mechanistically, SNX5 directly bound to Rab11a, increasing membrane accumulation of Rab11a (a Rab GTPase). Afterwards, this intricate molecular interaction upregulated the membrane content of low-density lipoprotein receptor-related protein 6 (LRP6), a key regulator against cardiac hypertrophy. Our comprehensive assessment of siRab11a expression in HL-1 cells revealed its role in antagonism of LRP6 membrane accumulation under SNX5 overexpression. CONCLUSIONS: This study revealed that binding of SNX5 with LRP6 triggers their membrane translocation through Rab11a assisting, defending against cardiac remodeling and cardiac dysfunction under pressure overload. These findings provide new insights into the previously unrecognized role of SNX5 in the progression of cardiac hypertrophy.

PredCoffee: A binary classification approach specifically for coffee odor.

Compared to traditional methods, using machine learning to assess or predict the odor of molecules can save costs in various aspects. Our research aims to collect molecules with coffee odor and summarize the regularity of these molecules, ultimately creating a binary classifier that can determine whether a molecule has a coffee odor. In this study, a total of 371 coffee-odor molecules and 9,700 non-coffee-odor molecules were collected. The Knowledge-guided Pre-training of Graph Transformer (KPGT), support vector machine (SVM), random forest (RF), multi-layer perceptron (MLP), and message-passing neural networks (MPNN) were used to train the data. The model with the best performance was selected as the basis of the predictor. The prediction accuracy value of the KPGT model exceeded 0.84 and the predictor has been deployed as a webserver PredCoffee.

A genome-wide association study reveals novel loci and candidate genes associated with plant height variation in Medicago sativa.

BACKGROUND: Plant height (PH) is an important agronomic trait influenced by a complex genetic network. However, the genetic basis for the variation in PH in Medicago sativa remains largely unknown. In this study, a comprehensive genome-wide association analysis was performed to identify genomic regions associated with PH using a diverse panel of 220 accessions of M. sativa worldwide. RESULTS: Our study identified eight novel single nucleotide polymorphisms (SNPs) significantly associated with PH evaluated in five environments, explaining 8.59-12.27% of the phenotypic variance. Among these SNPs, the favorable genotype of chr6__31716285 had a low frequency of 16.4%. Msa0882400, located proximal to this SNP, was annotated as phosphate transporter 3;1, and its role in regulating alfalfa PH was supported by transcriptome and candidate gene association analysis. In addition, 21 candidate genes were annotated within the associated regions that are involved in various biological processes related to plant growth and development. CONCLUSIONS: Our findings provide new molecular markers for marker-assisted selection in M. sativa breeding programs. Furthermore, this study enhances our understanding of the underlying genetic and molecular mechanisms governing PH variations in M. sativa.

Different Doses of Dexmedetomidine Reduce Postoperative Sleep Disturbance Incidence in Patients under General Anesthesia by Elevating Serum Neurotransmitter Levels.

Postoperative sleep disturbance is a common issue that affects recovery in patients undergoing general anesthesia. Dexmedetomidine (Dex) has a potential role in improving postoperative sleep quality. We evaluated the effects of different doses of Dex on postoperative sleep disturbance and serum neurotransmitters in patients undergoing radical gastrectomy under general anesthesia. Patients were assigned to the control, NS, and Dex (Dex-L/M/H) groups based on different treatment doses [0.2, 0.4, and 0.6 µg/(kg · h)]. The Athens Insomnia Scale (AIS) and ELISA kits were used to assess sleep disturbance and serum neurotransmitter (GABA, 5-HT, NE) levels before surgery and on postoperative days one, four, and seven. The effects of different doses on postoperative sleep disturbance incidence and serum neurotransmitter levels were analyzed by the Fisher exact test and one-way and repeated-measures ANOVA. Patients had no differences in gender, age, body mass index, operation time, and bleeding volume. Different Dex doses reduced the postoperative AIS score of patients under general anesthesia, improved their sleep, and increased serum levels of 5-HT, NE, and GABA. Furthermore, the effects were dose-dependent within the range of safe clinical use. Specifically, Dex at doses of 0.2, 0.4, and 0.6 µg/(kg · h) reduced postoperative AIS score, elevated serum neurotransmitter levels, and reduced postoperative sleep disturbance incidence. Collectively, Dex has a potential preventive effect on postoperative sleep disturbance in patients undergoing general anesthesia for radical gastrectomy. The optimal dose of Dex is between 0.2 and 0.6 µg/(kg · h), which significantly reduces the incidence of postoperative sleep disturbance and increases serum neurotransmitter levels.

Identification and Construction of a Disulfidptosis-Mediated Diagnostic Model and Associated Immune Microenvironment of Osteoarthritis from the Perspective of PPPM.

Background: Osteoarthritis (OA) is a major cause of human disability. Despite receiving treatment, patients with the middle and late stage of OA have poor survival outcomes. Therefore, within the framework of predictive, preventive, and personalized medicine (PPPM/3PM), early personalized diagnosis of OA is particularly prominent. PPPM aims to accurately identify disease by integrating multiple omic techniques; however, the efficiency of currently available methods and biomarkers in predicting and diagnosing OA should be improved. Disulfidptosis, a novel programmed cell death mechanism and appeared in particular metabolic status, plays a mysterious characteristic in the occurrence and development of OA, which warrants further investigation. Methods: In this study, we integrated three public datasets from the Gene Expression Omnibus (GEO) database, including 26 OA samples and 20 normal samples. Via a series of bioinformatic analysis and machine learning, we identified the diagnostic biomarkers and several subtypes of OA. Moreover, the expression of these biomarkers were verified in our in-house cohort and the single cell dataset. Results: Three significant regulators of disulfidptosis (NCKAP1, OXSM, and SLC3A2) were identified through differential expression analysis and machine learning. And a nomogram constructed based on these three regulators exhibited ideal efficiency in predicting early- and late-stage OA. Furthermore, based on the expression of three regulators, we identified two disulfidptosis-related subtypes of OA with different infiltration of immune cells and personalized expression level of immune checkpoints. Notably, the expression of the three regulators was demonstrated in a single-cell RNA profile and verified in the synovial tissue in our in-house cohort including 6 OA patients and 6 normal people. Finally, an efficient disulfidptosis-mediated diagnostic model was constructed for OA, with the AUC value of 97.6923% in the training set and 93.3333% and 100% in two validation sets. Conclusion: Overall, with regard to PPPM, this study provided novel insights into the role of disulfidptosis regulators in the personalized diagnosis and treatment of OA.

Effectiveness of home-based cardiac telerehabilitation based on wearable ECG or heart rate monitoring devices in patients with heart disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

A contrastive learning approach to integrate spatial transcriptomics and histological images.

The rapid growth of spatially resolved transcriptomics technology provides new perspectives on spatial tissue architecture. Deep learning has been widely applied to derive useful representations for spatial transcriptome analysis. However, effectively integrating spatial multi-modal data remains challenging. Here, we present ConGcR, a contrastive learning-based model for integrating gene expression, spatial location, and tissue morphology for data representation and spatial tissue architecture identification. Graph convolution and ResNet were used as encoders for gene expression with spatial location and histological image inputs, respectively. We further enhanced ConGcR with a graph auto-encoder as ConGaR to better model spatially embedded representations. We validated our models using 16 human brains, four chicken hearts, eight breast tumors, and 30 human lung spatial transcriptomics samples. The results showed that our models generated more effective embeddings for obtaining tissue architectures closer to the ground truth than other methods. Overall, our models not only can improve tissue architecture identification's accuracy but also may provide valuable insights and effective data representation for other tasks in spatial transcriptome analyses.

Prevalence and plasma exosome-derive microRNA diagnostic biomarker screening of adolescent idiopathic scoliosis in Yunnan Province, China.

Background: Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study. Methods: From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs. Results: The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value. Conclusions: We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

A Vacancy-Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co-Activated Immunotherapy.

Low efficacy of immunotherapy due to the poor immunogenicity of most tumors and their insufficient infiltration by immune cells highlights the importance of inducing immunogenic cell death and activating immune system for achieving better treatment outcomes. Herein, ferroelectric Bi2CuO4 nanoparticles with rich copper vacancies (named BCO-VCu) are rationally designed and engineered for ferroelectricity-enhanced apoptosis, cuproptosis, and the subsequently evoked immunotherapy. In this structure, the suppressed recombination of the electron-hole pairs by the vacancies and the band bending by the ferroelectric polarization lead to high catalytic activity, triggering reactive oxygen species bursts and inducing apoptosis. The cell fragments produced by apoptosis serve as antigens to activate T cells. Moreover, due to the generated charge by the ferroelectric catalysis, this nanomedicine can act as "a smart switch" to open the cell membrane, promote nanomaterial endocytosis, and shut down the Cu+ outflow pathway to evoke cuproptosis, and thus a strong immune response is triggered by the reduced content of adenosine triphosphate. Ribonucleic acid transcription tests reveal the pathways related to immune response activation. Thus, this study firstly demonstrates a feasible strategy for enhancing the efficacy of immunotherapy using single ferroelectric semiconductor-induced apoptosis and cuproptosis.

Chloramphenicol alleviates 5-fluorouracil-induced cellular senescence through activation of autophagy.

5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-ß-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer.

Focus on brain-lung crosstalk: Preventing or treating the pathological vicious circle between the brain and the lung.

Recently, there has been increasing attention to bidirectional information exchange between the brain and lungs. Typical physiological data is communicated by channels like the circulation and sympathetic nervous system. However, communication between the brain and lungs can also occur in pathological conditions. Studies have shown that severe traumatic brain injury (TBI), cerebral hemorrhage, subarachnoid hemorrhage (SAH), and other brain diseases can lead to lung damage. Conversely, severe lung diseases such as acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure can exacerbate neuroinflammatory responses, aggravate brain damage, deteriorate neurological function, and result in poor prognosis. A brain or lung injury can have adverse effects on another organ through various pathways, including inflammation, immunity, oxidative stress, neurosecretory factors, microbiome and oxygen. Researchers have increasingly concentrated on possible links between the brain and lungs. However, there has been little attention given to how the interaction between the brain and lungs affects the development of brain or lung disorders, which can lead to clinical states that are susceptible to alterations and can directly affect treatment results. This review described the relationships between the brain and lung in both physiological and pathological conditions, detailing the various pathways of communication such as neurological, inflammatory, immunological, endocrine, and microbiological pathways. Meanwhile, this review provides a comprehensive summary of both pharmacological and non-pharmacological interventions for diseases related to the brain and lungs. It aims to support clinical endeavors in preventing and treating such ailments and serve as a reference for the development of relevant medications.

Exploring Bitter and Sweet: The Application of Large Language Models in Molecular Taste Prediction.

The perception of bitter and sweet tastes is a crucial aspect of human sensory experience. Concerns over the long-term use of aspartame, a widely used sweetener suspected of carcinogenic risks, highlight the importance of developing new taste modifiers. This study utilizes Large Language Models (LLMs) such as GPT-3.5 and GPT-4 for predicting molecular taste characteristics, with a focus on the bitter-sweet dichotomy. Employing random and scaffold data splitting strategies, GPT-4 demonstrated superior performance, achieving an impressive 86% accuracy under scaffold partitioning. Additionally, ChatGPT was employed to extract specific molecular features associated with bitter and sweet tastes. Utilizing these insights, novel molecular compounds with distinct taste profiles were successfully generated. These compounds were validated for their bitter and sweet properties through molecular docking and molecular dynamics simulation, and their practicality was further confirmed by ADMET toxicity testing and DeepSA synthesis feasibility. This research highlights the potential of LLMs in predicting molecular properties and their implications in health and chemical science.

Co-expression network analysis and identification of core genes in the interaction between wheat and Puccinia striiformis f. sp. tritici.

The epidemic of stripe rust, caused by the pathogen Puccinia striiformis f. sp. tritici (Pst), would reduce wheat (Triticum aestivum) yields seriously. Traditional experimental methods are difficult to discover the interaction between wheat and Pst. Multi-omics data analysis provides a new idea for efficiently mining the interactions between host and pathogen. We used 140 wheat-Pst RNA-Seq data to screen for differentially expressed genes (DEGs) between low susceptibility and high susceptibility samples, and carried out Gene Ontology (GO) enrichment analysis. Based on this, we constructed a gene co-expression network, identified the core genes and interacted gene pairs from the conservative modules. Finally, we checked the distribution of Nucleotide-binding and leucine-rich repeat (NLR) genes in the co-expression network and drew the wheat NLR gene co-expression network. In order to provide accessible information for related researchers, we built a web-based visualization platform to display the data. Based on the analysis, we found that resistance-related genes such as TaPR1, TaWRKY18 and HSP70 were highly expressed in the network. They were likely to be involved in the biological processes of Pst infecting wheat. This study can assist scholars in conducting studies on the pathogenesis and help to advance the investigation of wheat-Pst interaction patterns.

The tricarboxylic acid cycle is inhibited under acute stress from carbonate alkalinity in the gills of Eriocheir sinensis.

Owing to population growth and environmental pollution, freshwater aquaculture has been rapidly shrinking in recent years. Aquaculture in saline-alkaline waters is a crucial strategy to meet the increasing demand for aquatic products. The Chinese mitten crab is an important economic food in China, but the molecular mechanism by which it tolerates carbonate alkalinity (CA) in water remains unclear. Here, we found that enzyme activities of the tricarboxylic acid (TCA) cycle in the gills, such as citrate synthase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase, were markedly reduced under CA stress induced by 40 mM NaHCO3. Secondly, the TCA cycle in the gills is inhibited under acute CA stress, according to proteomic and metabolomic analyses. The expressions of six enzymes, namely aconitate hydratase, isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase, dihydrolipoyl dehydrogenase, succinate-CoA ligase, and malate dehydrogenase, were downregulated, resulting in the accumulation of phosphoenolpyruvic acid, citric acid, cis-aconitate, and α-ketoglutaric acid. Finally, we testified that if the TCA cycle is disturbed by malonate, the survival rate increases in CA water. To our knowledge, this is the first study to show that the TCA cycle in the gills is inhibited under CA stress. Overall, the results provide new insights into the molecular mechanism of tolerance to saline-alkaline water in crabs, which helped us expand the area for freshwater aquaculture and comprehensively understand the physiological characteristics of crab migration.

Corrigendum: Effect of intravenous immunoglobulin therapy on the prognosis of patients with severe fever with thrombocytopenia syndrome and neurological complications.

[This corrects the article DOI: 10.3389/fimmu.2023.1118039.].

pathCLIP: Detection of Genes and Gene Relations from Biological Pathway Figures through Image-Text Contrastive Learning.

In biomedical literature, biological pathways are commonly described through a combination of images and text. These pathways contain valuable information, including genes and their relationships, which provide insight into biological mechanisms and precision medicine. Curating pathway information across the literature enables the integration of this information to build a comprehensive knowledge base. While some studies have extracted pathway information from images and text independently, they often overlook the correspondence between the two modalities. In this paper, we present a pathway figure curation system named pathCLIP for identifying genes and gene relations from pathway figures. Our key innovation is the use of an image-text contrastive learning model to learn coordinated embeddings of image snippets and text descriptions of genes and gene relations, thereby improving curation. Our validation results, using pathway figures from PubMed, showed that our multimodal model outperforms models using only a single modality. Additionally, our system effectively curates genes and gene relations from multiple literature sources. Two case studies on extracting pathway information from literature of non-small cell lung cancer and Alzheimer's disease further demonstrate the usefulness of our curated pathway information in enhancing related pathways in the KEGG database.

Venetoclax combined chemotherapy versus chemotherapy alone for acute myeloid leukemia: a systematic review and meta-analysis.

Objective: To compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML). Method: To compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs). Result: A total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group. Conclusion: The VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.