RESUMEN
Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.
RESUMEN
PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.
Asunto(s)
Autoanticuerpos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Nocardiosis , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Nocardiosis/inmunología , Nocardiosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Proteinosis Alveolar Pulmonar/inmunología , Proteinosis Alveolar Pulmonar/diagnóstico , Cryptococcus gattii/inmunologíaRESUMEN
PURPOSE: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. METHODS: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. RESULTS: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. CONCLUSION: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease.
Asunto(s)
Candidiasis Mucocutánea Crónica , Mutación con Ganancia de Función , Inmunofenotipificación , Pirazoles , Factor de Transcripción STAT1 , Humanos , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/diagnóstico , Candidiasis Mucocutánea Crónica/terapia , Masculino , Femenino , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Azetidinas/uso terapéutico , Purinas/uso terapéutico , Niño , Adolescente , Taiwán , AdultoRESUMEN
OBJECTIVE: To investigate which indicator is more advantageous when using arterial oxygen saturation (SaO2) and fingertip pulse oxygen saturation (SpO2) for blood oxygen detection in patients with hyperleukocytic acute leukemia (HAL). METHODS: In this prospective research, the difference between SaO2 and SpO2 of 18 HAL patients (observation group) and 14 patients (control group), as well as the relationship between the difference and white blood cell (WBC) counts were analyzed. RESULTS: SaO2 was lower than SpO2 in the observation group (P <0.05), and SpO2-SaO2 difference was positively correlated with WBC counts (r =0.47). However, there was no statistical difference between SaO2 and SpO2 in the control group. SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group, but there was no statistical difference. There was no downward trend of SaO2 and PO2 in the control group. CONCLUSION: HAL patients have a phenomenon where SaO2 is lower than SpO2, that is pseudohypoxemia, and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro SpO2 can be monitored bedside in real time and is non-invasive, it is a better way to detect the blood oxygen status of HAL patients.
Asunto(s)
Saturación de Oxígeno , Oxígeno , Humanos , Estudios Prospectivos , Oxígeno/sangre , Leucemia/sangre , Oximetría , Recuento de LeucocitosRESUMEN
OBJECTIVES: The study aimed to investigate the correlation between medial tibial slope (MTS) and lateral tibial slope (LTS) on magnetic resonance imaging (MRI), MTS measured by different imaging, and the intra- and interobserver reliability of measurements between reviewers with gaps of experience over 10 years. PATIENTS AND METHODS: This retrospective study included 97 patients (93 males, 4 females; mean age: 30.8±8.3 years; range, 17 to 49 years) with anterior cruciate ligament (ACL) injuries who subsequently underwent double-bundle ACL reconstruction by a single surgeon between January 2005 and December 2014. The MTS was measured on lateral knee radiographs, and MTS and LTS were measured on MRIs. Three different reviewers, including a postgraduate year doctor, an orthopedic resident, and an attending orthopedic surgeon, performed the measurements. Each reviewer measured the slope of the same image three times. The correlations of MTS on radiographs and MTS/LTS on MRIs were calculated. Intra- and interobserver reliability were evaluated. RESULTS: The average MTS and LTS measured on MRI were not significantly different (6.4° and 6.9°, respectively; p=0.268) and exhibited a moderate positive correlation (r=0.544, p<0.001). The average MTS on radiographs was significantly greater than that on MRI (10.5° and 6.4°, respectively; p<0.001) with a low positive correlation (r=0.480, p<0.001). The intraobserver reliability of the postgraduate year doctor, the orthopedic resident, and the attending orthopedic surgeon were moderate to excellent. The interobserver reliability of MTS on radiographs was excellent (intraclass correlation coefficient [ICC]=0.925; p<0.001). The interobserver reliability of MTS on MRI as well as LTS on MRI was good (ICC=0.755 and 820, respectively; all p values <0.001). CONCLUSION: Average MTS and LTS measured on MRI in patients with ACL injury exhibited a moderate positive correlation. The average MTS measured on radiographs was significantly greater than that on MRI with a low positive correlation.
Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Imagen por Resonancia Magnética , Tibia , Humanos , Femenino , Masculino , Imagen por Resonancia Magnética/métodos , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Adolescente , Estudios Retrospectivos , Adulto , Tibia/diagnóstico por imagen , Adulto Joven , Persona de Mediana Edad , Reproducibilidad de los Resultados , Reconstrucción del Ligamento Cruzado Anterior , Variaciones Dependientes del Observador , Radiografía/métodos , Articulación de la Rodilla/diagnóstico por imagen , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/cirugíaRESUMEN
Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is important for human bone formation. Long non-coding RNAs (lncRNAs) are critical regulators in osteogenic differentiation. This study aimed to explore the function and mechanisms of long intergenic non-protein coding RNA 963 (LINC00963) in affecting osteogenesis. Cell differentiation was assessed by alkaline phosphatase (ALP) activity detection and ALP staining assay. Meanwhile, levels of osteogenic marker genes, including RUNX family transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN), were detected by RT-qPCR and western blot. Cell proliferation and apoptosis were measured using CCK-8 assay and flow cytometry analysis. RNA immunoprecipitation (RIP), RNA pull-down and luciferase reporter assays were used to investigate the interaction between genes. LINC00963 expression was down-regulated in hBMSCs treated with osteogenic induction. LINC00963 overexpression inhibited hBMSCs differentiation, proliferation, and elevated apoptosis. LINC00963 acted as a competing endogenous RNA (ceRNA) to interact with miR-10b-5p and thereby regulated the expression level of Ras-related protein Rap-2a (RAP2A). LINC00963 regulated RAP2A to inhibit the level of phosphorylated AKT (p-AKT). LINC00963 inhibited hBMSCs differentiation, proliferation, and elevated apoptosis via the miR-10b-5p/RAP2A/AKT signaling, which might help improve the treatment of osteoporosis.
RESUMEN
Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated.
RESUMEN
This prospective crossover study aimed to investigate the effect of binaural beat therapy music on soccer player performance. Between July 2023 and December 2023, 45 athletes (31 females/14 males, mean age = 20.47 ± 0.99) wore Bluetooth earphones through which one of the following was given during initial 20 min warm-up exercises before undergoing repeated sprint ability tests: no music/fast-tempo music/fast-tempo music with background binaural beat therapy music. Heart rate change after warm-up exercises/repeated sprint ability (RSA) tests and the time to finish RSA tests were recorded. Despite no significant difference in heart rate increase after warm-up between the two genders regardless of intervention, larger increases after RSA tests were found in males following any of the three interventions (all p < 0.01) with the most notable difference observed after fast-tempo music (p < 0.0001). A significant effect size (r = 0.2) correlated with fast-tempo music during warm-up in either gender. Binaural beat therapy music during warm-up reached a significant effect size only when all participants were considered, suggesting limited benefits.
RESUMEN
Species of the family Microdochiaceae (Xylariales, Sordariomycetes) have been reported from worldwide, and collected from different plant hosts. The proposed new genus and two new species, viz., Macroidriella gen. nov., M.bambusae sp. nov. and Microdochiumaustrale sp. nov., are based on multi-locus phylogenies from a combined dataset of ITS rDNA, LSU, RPB2 and TUB2 with morphological characteristics. Microdochiumsinense has been collected from diseased leaves of Phragmitesaustralis and this is the first report of the fungus on this host plant. Simultaneously, we annotated 10,372 to 11,863 genes, identified 4,909 single-copy orthologous genes, and conducted phylogenomic analysis based on genomic data. A gene family analysis was performed and it will expand the understanding of the evolutionary history and biodiversity of the Microdochiaceae. The detailed descriptions and illustrations of species are provided.
RESUMEN
Lattice-confined single-atom catalyst (LC SAC), featuring exceptional activity, intriguing stability and prominent selectivity, has attracted extensive attention in the fields of various reactions (e.g., hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), etc.). To design a "smart" LC SAC for catalytic applications, one must systematically comprehend updated advances in the preparation, the application, and especially the peculiar electron regulation mechanism of LC SAC. In this review, the specific preparation methods of LC SAC based on general coordination strategy are updated, and its applications in HER, OER, ORR, N2 reduction reaction (NRR), advanced oxidation processes (AOPs) and so forth are summarized to display outstanding activity, stability and selectivity. Uniquely, the electron regulation mechanisms are first and deeply discussed and can be primarily categorized as electron transfer bridge with monometallic active sites, novel catalytic centers with polymetallic active sites, and positive influence by surrounding environments. In the end, the existing issues and future development directions are put forward with a view to further optimize the performance of LC SAC. This review is expected to contribute to the in-depth understanding and practical application of highly efficient LC SAC.
RESUMEN
Minimization of cadmium (Cd) accumulation in wheat grain (Triticum aestivum L.) is an important way to prevent Cd hazards to humans. However, little is known about the mechanisms of varietal variation of Cd accumulation in wheat grain. This study explores the physiological mechanisms of Cd bioaccumulation through field and hydroponic experiments on two wheat varieties of low-Cd-accumulating variety (L-6331) and high-Cd-accumulating variety (H-6049). Field study showed that average Cd accumulative rates in spikes of H-6049 were 1.57-fold of L-6331 after flowering, ultimately grain-Cd of H-6049 was 1.70-fold of L-6331 in Cd-contaminated farmland. The hydroponic experiment further confirmed that more vegetative tissues of L-6331 were involved in the remobilization of Cd, which jointly mitigated the process of Cd loaded to grains when leaf-cutting conducted after Cd stress. Additionally, the L1 and N1 of L-6331 play an especially important role in regulating Cd remobilization, and the larger EVB areas in N1 have the morphological feature that facilitates the transfer of Cd to L1. Overall results implied that low-Cd-accumulating variety initiated more trade-offs of reproductive growth and Cd remobilizatoin under Cd-stress after flowering compared with high-Cd-accumulating variety, and provided new insights into the processes of Cd loaded into wheat grains among different varieties.
Asunto(s)
Cadmio , Contaminantes del Suelo , Triticum , Triticum/metabolismo , Triticum/crecimiento & desarrollo , Cadmio/metabolismo , Contaminantes del Suelo/metabolismo , Bioacumulación , Reproducción , Grano Comestible/metabolismo , Grano Comestible/crecimiento & desarrolloRESUMEN
BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.
RESUMEN
Infectious laryngotracheitis (ILT) poses a significant threat to the poultry industry, and vaccines play an important role in protection. However, due to the increasing scale of poultry production, there is an urgent need to develop vaccines that are suitable for convenient immunization methods such as spraying. Previous studies have shown that Newcastle disease virus (NDV)-ILT vaccines administered via intranasal and intraocular routes to commercial chickens carrying maternally-derived antibodies (MDAs) are still protective against ILT. In this study, a recombinant NDV (rNDV) was generated to express infectious laryngotracheitis virus (ILTV) glycoprotein B (gB), named rLS-gB, based on a full-length cDNA clone of the LaSota strain. The protective effect of different doses of rLS-gB administered by spray vaccination to commercial chickens at 1 d of age (doa) was evaluated. The chickens were exposed to 160-µm aerosol particles for 10â min for spray vaccination, and no adverse reactions were observed after vaccination. Despite the presence of anti-NDV MDAs and anti-ILTV MDAs in chickens, the ILTV- and NDV-specific antibody titres were significantly greater in the vaccinated groups than in the unvaccinated group. After challenge with a virulent ILTV strain, no clinical signs were observed in the 107 EID50/ml group compared to the other groups. Furthermore, vaccination with 107 EID50/ml rLS-gB significantly reduced the ILTV viral load and ameliorated gross and microscopic lesions in the trachea of chickens. Overall, these results suggested that rLS-gB is a safe and efficient candidate spray vaccine for ILT and is especially suitable for scaled chicken farms.
RESUMEN
Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.
RESUMEN
OBJECTIVE: Our objective was to create a machine learning architecture capable of identifying obstructive sleep apnea (OSA) patterns in single-lead electrocardiography (ECG) signals, exhibiting exceptional performance when utilized in clinical data sets. METHODS: We conducted our research using a data set consisting of 1656 patients, representing a diverse demographic, from the sleep center of China Medical University Hospital. To detect apnea ECG segments and extract apnea features, we utilized the EfficientNet and some of its layers, respectively. Furthermore, we compared various training and data preprocessing techniques to enhance the model's prediction, such as setting class and sample weights or employing overlapping and regular slicing. Finally, we tested our approach against other literature on the Apnea-ECG database. RESULTS: Our research found that the EfficientNet model achieved the best apnea segment detection using overlapping slicing and sample-weight settings, with an AUC of 0.917 and an accuracy of 0.855. For patient screening with AHI > 30, we combined the trained model with XGBoost, leading to an AUC of 0.975 and an accuracy of 0.928. Additional tests using PhysioNet data showed that our model is comparable in performance to existing models regarding its ability to screen OSA levels. CONCLUSIONS: Our suggested architecture, coupled with training and preprocessing techniques, showed admirable performance with a diverse demographic dataset, bringing us closer to practical implementation in OSA diagnosis. Trial registration The data for this study were collected retrospectively from the China Medical University Hospital in Taiwan with approval from the institutional review board CMUH109-REC3-018.
Asunto(s)
Electrocardiografía , Aprendizaje Automático , Procesamiento de Señales Asistido por Computador , Síndromes de la Apnea del Sueño , Humanos , Masculino , Persona de Mediana Edad , Síndromes de la Apnea del Sueño/diagnóstico , Femenino , Adulto , Anciano , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatologíaRESUMEN
The industrialization of animal agriculture has undoubtedly contributed to the improvement of human well-being by increasing the efficiency of food animal production. At the same time, it has also drastically impacted the natural environment and human society. The One Health initiative emphasizes the interdependency of the health of ecosystems, animals, and humans. In this paper, we discuss some of the most profound consequences of animal agriculture practices from a One Health perspective. More specifically, we focus on impacts to host-microbe interactions by elaborating on how modern animal agriculture affects zoonotic infections, specifically those of bacterial origin, and the concomitant emergence of antimicrobial resistance (AMR). A key question underlying these deeply interconnected issues is how to better prevent, monitor, and manage infections in animal agriculture. To address this, we outline approaches to mitigate the impacts of agricultural bacterial zoonoses and AMR, including the development of novel treatments as well as non-drug approaches comprising integrated surveillance programs and policy and education regarding agricultural practices and antimicrobial stewardship. Finally, we touch upon additional major environmental and health factors impacted by animal agriculture within the One Health context, including animal welfare, food security, food safety, and climate change. Charting how these issues are interwoven to comprise the complex web of animal agriculture's broad impacts on One Health will allow for the development of concerted, multidisciplinary interventions which are truly necessary to tackle these issues from a One Health perspective.
RESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairments, and behavioral changes. The presence of abnormal beta-amyloid plaques and tau protein tangles in the brain is known to be associated with AD. However, current limitations of imaging technology hinder the direct detection of these substances. Consequently, researchers are exploring alternative approaches, such as indirect assessments involving monitoring brain signals, cognitive decline levels, and blood biomarkers. Recent studies have highlighted the potential of integrating genetic information into these approaches to enhance early detection and diagnosis, offering a more comprehensive understanding of AD pathology beyond the constraints of existing imaging methods. Our study utilized electroencephalography (EEG) signals, genotypes, and polygenic risk scores (PRSs) as features for machine learning models. We compared the performance of gradient boosting (XGB), random forest (RF), and support vector machine (SVM) to determine the optimal model. Statistical analysis revealed significant correlations between EEG signals and clinical manifestations, demonstrating the ability to distinguish the complexity of AD from other diseases by using genetic information. By integrating EEG with genetic data in an SVM model, we achieved exceptional classification performance, with an accuracy of 0.920 and an area under the curve of 0.916. This study presents a novel approach of utilizing real-time EEG data and genetic background information for multimodal machine learning. The experimental results validate the effectiveness of this concept, providing deeper insights into the actual condition of patients with AD and overcoming the limitations associated with single-oriented data.
Asunto(s)
Enfermedad de Alzheimer , Electroencefalografía , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Humanos , Electroencefalografía/métodos , Femenino , Masculino , Aprendizaje Automático , Máquina de Vectores de Soporte , Anciano , Procesamiento de Señales Asistido por Computador , AlgoritmosRESUMEN
TH1L (also known as NELF-C/D) is a member of the Negative Elongation Factor (NELF) complex, which is a metazoan-specific factor that regulates RNA Polymerase II (RNAPII) pausing and transcription elongation. However, the function and molecular mechanisms of TH1L in cancer progression are still largely unknown. In this study, we found that TH1L was highly expressed in colorectal cancer (CRC) tissues and the faeces of CRC patients. Overexpression of TH1L significantly enhanced the proliferation and migration of CRC cells, while its knockdown markedly suppressed these processes. In mechanism, RNA sequencing revealed that CCL20 was upregulated in TH1L-overexpressed CRC cells, leading to activation of the NF-κB signalling pathway. Rescue assays showed that knockdown of CCL20 could impair the tumour-promoting effects of THIL in CRC cells. Taken together, these results suggest that TH1L may play a vital role via the CCL20/NF-κB signalling pathway in CRC proliferation and migration and may serve as a potential target for diagnosis and therapy of CRC.
Asunto(s)
Movimiento Celular , Proliferación Celular , Quimiocina CCL20 , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , FN-kappa B , Transducción de Señal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Línea Celular Tumoral , Movimiento Celular/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , FN-kappa B/metabolismoRESUMEN
Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.