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Around the world, suicide ideation, attempts, and deaths pose a major public and mental health challenge for patients (and their loved ones). Accordingly, there is a clear need for effective clinical treatments that reliably reduce suicidal thoughts and behaviors. In this article, we review the Collaborative Assessment and Management of Suicidality (CAMS) and Dialectical Behavior Therapy (DBT), two clinical treatments that rise to the highest levels of empirical rigor. Both CAMS and DBT are now supported by randomized controlled trials (RCTs), with independent replications, and meta-analyses. There are also supportive data related to training clinical providers to use CAMS and DBT with adherence. RCTs that investigate the use of both interventions within clinical trial research designs and the increasing use of these complementary approaches within routine clinical practice are discussed. Future directions for research and clinical use of CAMS and DBT are explored as means to effectively treat suicidal risk.
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Neuroblastoma (NB) is the most prevalent extracranial solid tumor in pediatric patients, and its treatment failure often associated with metastasis. In this study, LASSO, SVM-RFE, and random forest tree algorithms, was used to identify the pivotal gene involved in NB metastasis. NB cell lines (SK-N-AS and SK-N-BE2), in conjunction with NB tissue were used for further study. ABLIM3 was identified as the hub gene and can be an independent prognostic factor for patients with NB. The immunohistochemical analysis revealed that ABLIM3 is negatively correlated with the metastasis of NB. Patients with low expression of ABLIM3 had a poor prognosis. High ABLIM3 expression correlated with APC co-stimulation and Type1 IFN response, and TIDE analysis indicated that patients with low ABLIM3 expression exhibited enhanced responses to immunotherapy. Downregulation of ABLIM3 by shRNA transfection increased the migration and invasion ability of NB cells. Gene Set Enrichment Analysis (GSEA) revealed that genes associated with ABLIM3 were primarily enriched in the cell adhesion molecules (CAMs) pathway. RT-qPCR and western blot analyses demonstrated that downregulation of ABLIM3 led to decreased expression of ITGA3, ITGA8, and KRT19, the key components of CAMs. This study indicated that ABLIM3 can be an independent prognostic factor for NB patients, and CAMs may mediate the effect of ABLIM3 on the metastasis of NB, suggesting that ABLIM3 is a potential therapeutic target for NB metastasis, which provides a novel strategy for future research and treatment strategies for NB patients.
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Extreme aerosol pollution poses significant risks to the climate, environment, and human health. To investigate the formation and impacts of aerosol pollution extreme events (APEE), the reanalysis product presents meticulous spatiotemporal information on the three-dimensional distribution of aerosols. However, there is a lack of comprehensive evaluation and information regarding the data quality of reanalysis products employed in APEE research, as well as limited understanding of their spatial and temporal distribution, variation, and long-term trends. To address this scientific gap, we conducted a global study for distribution and variation patterns of APEE using two widely-used reanalysis products, MERRA-2 (Modern-Era Retrospective Analysis for Research-2) and CAMS (Copernicus Atmospheric Monitoring Service). The APEE was defined here as a day when the daily aerosol optical depth (AOD) exceeding its 90th percentile for a given station and month. Eleven distinct land regions worldwide were selected for evaluation by comparing both reanalysis products with MODIS satellite products and ground-based observations in terms of frequency, intensity, and temporal trends of APEE. The analysis indicates that MERRA-2 and CAMS exhibit high matching rates (70 % and 80 %, respectively) in terms of occurrence timeline for APEE at monthly and seasonal scales, while also exhibiting strong monthly correlation coefficients (>0.65) with ground-based observations over selected regions. The total AOD (-0.002 â¼ -0.123 decade-1), APEE AOD (-0.004 â¼ -0.293 decade-1), and APEE frequency (-0.264 â¼ -1.769 day month-1 decade-1) of both observations and reanalysis products in most regions showed a decreasing trend with various magnitude, except for some regions such as South Asia where the trend is increasing. Based on the aforementioned evaluation, it is evident that reanalysis products are effective and useful in identifying the temporal trends associated with APEE.
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Although the use of immune checkpoint inhibitors (ICIs)-targeted agents for unresectable hepatocellular carcinoma (HCC) is promising, individual response variability exists. Therefore, we developed an artificial intelligence (AI)-based model to predict treatment efficacy using pre-ICIs contrast-enhanced computed tomography (CT) imaging characteristics. We evaluated the efficacy of atezolizumab and bevacizumab in 43 patients at the Nagasaki University Hospital from 2020 to 2022 using the modified Response Evaluation Criteria in Solid Tumors. A total of 197 Progressive Disease (PD), 271 Partial Response (PR), and 342 Stable Disease (SD) contrast CT images of HCC were used for training. We used ResNet-18 as the Convolutional Neural Network (CNN) model and YOLOv5, YOLOv7, YOLOv8 as the You Only Look Once (YOLO) model with precision-recall curves and class activation maps (CAMs) for diagnostic performance evaluation and model interpretation, respectively. The 3D t-distributed Stochastic Neighbor Embedding was used for image feature analysis. The YOLOv7 model demonstrated Precision 53.7%, Recall 100%, F1 score 69.8%, mAP@0.5 99.5% for PD, providing accurate and clinically versatile predictions by identifying decisive points. The ResNet-18 model had Precision 100% and Recall 100% for PD. However, the CAMs sites did not align with the tumors, suggesting the CNN model is not predicting that a given CT slice is PD, PR, or SD, but that it accurately predicts Individual Patient's CT slices. Preparing substantial training data for tumor drug effect prediction models is challenging compared to general tumor diagnosis models; hence, large-scale validation using an efficient YOLO model is warranted.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Inteligência Artificial , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Cerebrofacial arteriovenous Metameric syndrome (CAMS) typically manifests as types I, II, or III, occasionally presenting as dual types. Our unique case underscores the coexistence of all three CAMS types in one patient. Furthermore, the concurrent acute cerebellar infarct underscores the need to consider CAMS in the differential diagnosis of adolescents experiencing neurological events.
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Aerosol optical depth (AOD) is an essential metric for evaluating the atmospheric aerosol load and its impacts on climate, air quality, and public health. In this study, the AOD data from the Copernicus Atmosphere Monitoring Service (CAMS) were validated against ground-based measurements from the Aerosol Robotic Network (AERONET) throughout the Eastern Mediterranean, a region characterized by diverse aerosol types and sources. A comparative analysis was performed on 3-hourly CAMS AOD values at 550 nm against observations from 20 AERONET stations across Cyprus, Greece, Israel, Egypt, and Turkey from 2003 to 2021. The CAMS AOD data exhibited a good overall agreement with AERONET AOD data, demonstrated by a Pearson correlation coefficient of 0.77, a mean absolute error (MAE) of 0.08, and a root mean square error (RMSE) of 0.11. Nonetheless, spatial and temporal variations were observed in the CAMS AOD data performance, with site-specific correlation coefficients ranging from 0.57 to 0.85, the lowest correlations occurring in Egypt and the highest in Greece. An underestimation of CAMS AOD was noted at inland sites with high AOD levels, while a better agreement was observed at coastal sites with lower AOD levels. The diurnal variation analysis indicated improved CAMS reanalysis performance during the afternoon and evening hours. Seasonally, CAMS reanalysis showed better agreement with AERONET AODs in spring and autumn, with lower correlation coefficients noted in summer and winter. This study marks the first comprehensive validation of CAMS AOD performance in the Eastern Mediterranean, offering significant enhancements for regional air quality and climate modeling, and underscores the essential role of consistent validation in refining aerosol estimations within this complex and dynamic geographic setting.
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Aerossóis , Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Aerossóis/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Atmosfera/química , Região do Mediterrâneo , GréciaRESUMO
OBJECTIVES: This research aims to comparatively investigate the capability of resveratrol (RES) and RES analogues, oxyresveratrol (Oxy-RES) and dihydrooxyresveratrol (DHoxy-RES), to potentiate doxorubicin (DOX) effects against lung carcinoma epithelial cells. METHODS: All experiments were performed on lung carcinoma cell lines (A549) with DOX combination between DOX and RES or RES analogues. Cell viability or growth inhibitory effect was assessed by MTT assay and genes associated with survival and metastasis were monitored by real-time polymerase chain reaction (RT-PCR). RESULTS: DOX obviously demonstrated cytotoxic and anti-metastatic activities against A549 cells. Expression of gene-associated with both activities was potentiated by RES and RES analogues. Oxy-RES showed highest capability to potentiate DOX effects. DHoxy-RES showed nearly no effect to DOX activities. CONCLUSIONS: These results provided an important basis of DOX combination with RES analogues, especially Oxy-RES, for better therapeutic effect. Further studies in human should be performed on exploring combination of DOX and Oxy-RES.
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Carcinoma , Neoplasias Pulmonares , Extratos Vegetais , Estilbenos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Resveratrol/farmacologia , Doxorrubicina/farmacologia , Pulmão/patologia , Linhagem Celular Tumoral , ApoptoseRESUMO
Methane (CH4) is the second most abundant greenhouse gas after CO2, which plays the most important role in global and regional climate change. To explore the long-term spatiotemporal variations of near-surface CH4, datasets were extracted from Greenhouse gases Observing SATellite (GOSAT), and the Copernicus Atmospheric Monitoring Service (CAMS) reanalyzed datasets from June 2009 to September 2020 over South, East, and Southeast Asia. The accuracy of near-surface CH4 from GOSAT and CAMS was verified against surface observatory stations available in the study region to confirm both dataset applicability and results showed significant correlations. Temporal plots revealed continuous inflation in the near-surface CH4 with a significant seasonal and monthly variation in the study region. To explore the factors affecting near-surface CH4 distribution, near-surface CH4 relationship with anthropogenic emission, NDVI data, wind speed, temperature, precipitation, soil moisture, and relative humidity were investigated. The results showed a significant contribution of anthropogenic emissions with near-surface CH4. Regression and correlation analysis showed a significant positive correlation between NDVI data and near-surface CH4 from GOSAT and CAMS, while a significant negative correlation was found between wind and near-surface CH4. In the case of temperature, soil moisture, and near-surface CH4 from GOSAT and CAMS over high CH4 regions of the study area showed a significant positive correlation. However significant negative correlations were found between precipitation and relative humidity with GOSAT and CAMS datasets over high CH4 regions in South, East, and Southeast Asia. Moreover, these climatic factors showed no significant correlation within the low near-surface CH4 areas in our study region. Our study results showed that anthropogenic emissions, NDVI data, wind speed, temperature, precipitation, soil moisture, and humidity could significantly affect the near-surface CH4 over South, East, and Southeast Asia.
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Glucosidase II beta subunit (GluIIß), encoded from PRKCSH, is a subunit of the glucosidase II enzyme responsible for quality control of N-linked glycoprotein folding and suppression of GluIIß led to inhibitory effect of the receptor tyrosine kinase (RTKs) activities known to be critical for survival and development of cancer. In this study, we investigated the effect of GluIIß knockout on the global gene expression of cancer cells and its impact on functions of immune cells. GluIIß knockout lung adenocarcinoma A549 cell line was generated using CRISPR/Cas9-based genome editing system and subjected to transcriptomic analysis. Among 23,502 expressed transcripts, 1068 genes were significantly up-regulated and 807 genes greatly down-regulated. The KEGG enrichment analysis showed significant down-regulation of genes related extracellular matrix (ECM), ECM-receptor interaction, cytokine-cytokine receptor interaction and cell adhesion molecules (CAMs) in GluIIß knockout cells. Of 9 CAMs encoded DEG identified by KEGG enrichment analysis, real time RT-PCR confirmed 8 genes to be significantly down-regulated in all 3 different GluIIß knockout clones, which includes cadherin 4 (CDH4), cadherin 2 (CDH2), versican (VCAN), integrin subunit alpha 4 (ITGA4), endothelial cell-selective adhesion molecule (ESAM), CD274 (program death ligand-1 (PD-L1)), Cell Adhesion Molecule 1 (CADM1), and Nectin Cell Adhesion Molecule 3 (NECTIN3). Whereas PTPRF (Protein Tyrosine Phosphatase Receptor Type F) was significantly decreased only in 1 out of 3 knockout clones. Microscopic analysis revealed distinctively different cell morphology of GluIIß knockout cells with lesser cytoplasmic and cell surface area compared to parental A549 cells and non-targeted transfected cells.Further investigations revealed that Jurkat E6.1 T cells or human peripheral blood mononuclear cells (PBMCs) co-cultured with GluIIß knockout A549 exhibited significantly increased viability and tumor cell killing activity compared to those co-cultured with non-target transfected cells. Analysis of cytokine released from Jurkat E6.1 T cells co-cultured with GluIIß knockout A549 cells showed significant increased level of angiogenin and significant decreased level of ENA-78. In conclusion, knockout of GluIIß from cancer cells induced altered gene expression profile that improved anti-tumor activities of co-cultured T lymphocytes and PBMCs thus suppression of GluIIß may represent a novel approach of boosting anti-tumor immunity.
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Moléculas de Adesão Celular , Leucócitos Mononucleares , alfa-Glucosidases , Humanos , Células A549 , Moléculas de Adesão Celular/genética , Perfilação da Expressão Gênica , Citocinas , Adesão Celular , Molécula 1 de Adesão CelularRESUMO
Black carbon (BC) constitutes a pivotal component of atmospheric aerosols, significantly impacting regional and global radiation balance, climate, and human health. In this study, we evaluated BC data in two prominent atmospheric composition reanalysis datasets: the Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2) and the Copernicus Atmosphere Monitoring Service (CAMS), and analyzed the causes of their deviations. This assessment is based on observational data collected from 34 monitoring stations across China from 2006 to 2022. Our research reveals a significant and consistent decline in BC concentrations within China, amounting to a reduction exceeding 67.33%. However, both MERRA-2 and CAMS reanalysis data fail to capture this declining trend. The average annual decrease of BC in MERRA-2 from 2006 to 2022 is only 0.06 µg/m3 per year, while the BC concentration in CAMS even increased with an average annual value of 0.014 µg/m3 per year. In 2022, MERRA-2 had overestimated BC concentration by 20% compared to observational data, while CAMS had overestimated it by approximately 66%. In the regional BC concentration analysis, the data quality of the reanalysis data is better in the South China (RM = 0.59, RC = 0.53), followed by the North China (RM = 0.50, RC = 0.42). Reanalysis BC data in Northwest China and the Tibetan Plateau are difficult to use for practical analysis due to their big difference with observation. In a comparison of the anthropogenic BC emissions inventory used in the two atmospheric composition reanalysis datasets with the Multi-resolution Emission Inventory model for Climate and air pollution research (MEIC) emissions inventory, we found that: Despite the significant decline in China's BC emissions, MERRA-2 still relies on the 2006 emissions inventory, while CAMS utilizes emission inventories that even show an increasing trend. These factors will undoubtedly lead to greater deviations between reanalysis and observational data.
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Poluentes Atmosféricos , Humanos , Poluentes Atmosféricos/análise , Estudos Retrospectivos , China , Atmosfera/análise , Aerossóis/análise , Fuligem/análise , Carbono/análise , Monitoramento AmbientalRESUMO
Background: Suicide rates in the United States have escalated dramatically over the past 20 years and remain a leading cause of death. Access to evidenced-based care is limited, and telehealth is well-positioned to offer novel care solutions. The Crisis Care program is a suicide-specific treatment program delivered within a national outpatient telehealth setting using a digitally adapted version of the Collaborative Assessment and Management of Suicidality (CAMS) as the framework of care. This study investigates the feasibility and preliminary effectiveness of Crisis Care as scalable suicide-specific treatment model. Methods: Patient engagement, symptom reduction, and care outcomes were examined among a cohort of patients (n = 130) over 16 weeks. The feasibility of implementation was assessed through patient engagement. Clinical outcomes were measured with PHQ-9, GAD-7, and the CAMS SSF-4 rating scales. Results: Over 85% of enrolled patients were approved for Crisis Care at intake, and 83% went on to complete at least four sessions (the minimum required to graduate). All patient subgroups experienced declines in depressive symptoms, anxiety symptoms, suicidal ideation frequency, and suicide-specific risk factors. Conclusions: Results support the feasibility and preliminary effectiveness of Crisis Care as a suicide-specific care solution that can be delivered within a stepped-care model in an outpatient telehealth setting.
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Hepatitis B virus (HBV) is the primary contributor to severe liver ailments, encompassing conditions such as cirrhosis and hepatocellular carcinoma. Globally, 257 million people are affected by HBV annually and 887,000 deaths are attributed to it, representing a substantial health burden. Regrettably, none of the existing therapies for chronic hepatitis B (CHB) have achieved satisfactory clinical cure rates. This issue stems from the existence of covalently closed circular DNA (cccDNA), which is difficult to eliminate from the nucleus of infected hepatocytes. HBV genetic material is composed of partially double-stranded DNA that forms complexes with viral polymerase inside an icosahedral capsid composed of a dimeric core protein. The HBV core protein, consisting of 183 to 185 amino acids, plays integral roles in multiple essential functions within the HBV replication process. In this review, we describe the effects of sulfamoyl-based carboxamide capsid assembly modulators (CAMs) on capsid assembly, which can suppress HBV replication and disrupt the production of new cccDNA. We present research on classical, first-generation sulfamoyl benzocarboxamide CAMs, elucidating their structural composition and antiviral efficacy. Additionally, we explore newly identified sulfamoyl-based CAMs, including sulfamoyl bicyclic carboxamides, sulfamoyl aromatic heterocyclic carboxamides, sulfamoyl aliphatic heterocyclic carboxamides, cyclic sulfonamides, and non-carboxamide sulfomoyl-based CAMs. We believe that certain molecules derived from sulfamoyl groups have the potential to be developed into essential components of a well-suited combination therapy, ultimately yielding superior clinical efficacy outcomes in the future.
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Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/metabolismo , Antivirais/uso terapêutico , Nucleocapsídeo/metabolismo , Hepatite B Crônica/tratamento farmacológico , Capsídeo/metabolismo , Proteínas do Capsídeo/genética , DNA Circular/genética , DNA Circular/metabolismo , Replicação Viral , DNA Viral/genética , DNA Viral/metabolismo , Hepatite B/tratamento farmacológico , Hepatite B/metabolismoRESUMO
Climacteric is characterized as the set of symptoms that usually start in the period of transition from the reproductive phase to female senility, and directly impacts woman's quality of life. Currently, the treatments approved by the FDA for this pathology mainly involve the use of antidepressants and hormone replacement, both having side effects. Clinical studies carried out in 2002, showed an increased risk of breast cancer, and other pathologies related to the prolonged use of these drugs. The impact ofthe studies resulted in a greater interest in complementary and alternative medicines (CAMs), such as the use of homeopathy and flower remedies for the treatment of climacteric symptoms. This abstract aims to present an integrative review on the use of homeopathy and flower remedies in the treatment of climacteric symptoms, in order to identify it main scientific evidence. For this, metodology consisted of research in the databases Web of Science, Google Scholar, HomeoIndex, LILACS and SciELO. The inclusion criteria were original human studies, totally available, and published in the last 10 years in Portuguese, English and Spanish, presenting the use of floral remedies or homeopathic treatment. The main homeopathic medicines used were Lachesis mutus, Belladona, Sepia officinalis, Sanguinaria canadensis and Sulfur. The main flower remedies were Cherry plum, Agrimony, Gentian, Walnut, Olive and Larch. The findings in this review demonstrate a positive outcome trend in favor of the effectiveness of these practices through the studies evaluated, encouraging the expansion of new designs and research that fully contemplate the principles of these practices. Thus, this work contributes to the advancement in the understanding of each one of these rationalities, making this work a source of consultation for health professionals and for future research, resulting in a strengthening of CAMs in the field of health.