RESUMEN
Pathogen-responsive immune-related genes (resistance genes [R-genes]) and hormones are crucial mediators of systemic acquired resistance (SAR). However, their integrated functions in regulating SAR signaling components in local and distal leaves remain largely unknown. To characterize SAR in the Xanthomonas campestris pv. campestris (Xcc)-Brassica napus pathosystem, the responses of R-genes, (leaf and phloem) hormone levels, H2O2 levels, and Ca2+ signaling-related genes were assessed in local and distal leaves of plants exposed to four Xcc-treatments: Non-inoculation (control), only secondary Xcc-inoculation in distal leaves (C-Xcc), only primary Xcc-inoculation in local leaves (Xcc), and both primary and secondary Xcc-inoculation (X-Xcc). The primary Xcc-inoculation provoked disease symptoms as evidenced by enlarged destructive necrosis in the local leaves of Xcc and X-Xcc plants 7 days post-inoculation. Comparing visual symptoms in distal leaves 5 days post-secondary inoculation, yellowish necrotic lesions were clearly observed in non Xcc-primed plants (C-Xcc), whereas no visual symptom was developed in Xcc-primed plants (X-Xcc), demonstrating SAR. Pathogen resistance in X-Xcc plants was characterized by distinct upregulations in expression of the PAMP-triggered immunity (PTI)-related kinase-encoding gene, BIK1, the (CC-NB-LRR-type) R-gene, ZAR1, and its signaling-related gene, NDR1, with a concurrent enhancement of the kinase-encoding gene, MAPK6, and a depression of the (TIR-NB-LRR-type) R-gene, TAO1, and its signaling-related gene, SGT1, in distal leaves. Further, in X-Xcc plants, higher salicylic acid (SA) and jasmonic acid (JA) levels, both in phloem and distal leaves, were accompanied by enhanced expressions of the SA-signaling gene, NPR3, the JA-signaling genes, LOX2 and PDF1.2, and the Ca2+-signaling genes, CAS and CBP60g. However, in distal leaves of C-Xcc plants, an increase in SA level resulted in an antagonistic depression of JA, which enhanced only SA-dependent signaling, EDS1 and NPR1. These results demonstrate that primary Xcc-inoculation in local leaves induces resistance to subsequent pathogen attack by upregulating BIK1-ZAR1-mediated synergistic interactions with SA and JA signaling as a crucial component of SAR.
RESUMEN
Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.
RESUMEN
In this review by TC- 282 CCL, a comprehensive examination of various facets of chloride ingress in calcined clay-based concrete in aggressive chloride-rich environments is presented due to its significance in making reinforced concrete structures susceptible to chloride-induced corrosion damages. The review presents a summary of available literature focusing on materials characteristics influencing the chloride resistance of calcined clay-based concrete, such as different clay purity, kaolinite content and other clay minerals, underscoring the significance of pore refinement, pore solution composition, and chloride binding mechanisms. Further, the studies dealing with the performance at the concrete scale, with a particular emphasis on transport properties, curing methods, and mix design, are highlighted. Benchmarking calcined clay mixes with fly ash or slag-based concrete mixes that are widely used in aggressive chloride conditions instead of OPC is recommended. Such comparison could extend the usage of calcined clay as a performance-enhancing mineral admixture in the form of calcined clay or LC2 (limestone-calcined clay). The chloride diffusion coefficient in calcined clay concrete is reported to be significantly lower (about 5-10 times in most literature available so far) compared to OPC, and even lower compared to fly ash and slag-based concrete at early curing ages reported across recent literature made with different types of cements and concrete mixes. Limited studies dealing with reinforcement corrosion point out that calcined clay delays corrosion initiation and reduces corrosion rates despite the reduction in critical chloride threshold. Most of these results on corrosion performance are mainly from laboratory studies and warrant field evaluation in future. Finally, two case studies demonstrating the application of calcined clay-based concrete in real-world marine exposure conditions are discussed to showcase the promising potential of employing low-purity calcined clay-based concrete for reducing carbon footprint and improving durability performance in chloride exposure.
RESUMEN
OBJECTIVES: To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD). METHODS: Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth's penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD. RESULTS: A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16-3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11-45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00-57.36) were identified as risk factors for mortality in RA-ILD patients. CONCLUSION: Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD.
Asunto(s)
Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Enfermedades Pulmonares Intersticiales/mortalidad , Artritis Reumatoide/mortalidad , Artritis Reumatoide/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios Prospectivos , Anciano , República de Corea/epidemiología , Estudios de Cohortes , AdultoRESUMEN
Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD+ homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P)+ and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.
Asunto(s)
Toxinas Bacterianas , Microscopía por Crioelectrón , Vibrio vulnificus , Vibrio vulnificus/metabolismo , Vibrio vulnificus/patogenicidad , Animales , Humanos , Ratones , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/química , Femenino , NAD/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sepsis/microbiología , Dominios Proteicos , Vibriosis/microbiología , NAD+ Nucleosidasa/metabolismo , NAD+ Nucleosidasa/química , Cristalografía por Rayos XRESUMEN
[This corrects the article DOI: 10.1016/j.jgr.2019.05.003.].
RESUMEN
BACKGROUND: The homing of human mesenchymal stem cells (hMSCs) is crucial for their therapeutic efficacy and is characterized by the orchestrated regulation of multiple signaling modules. However, the principal upstream regulators that synchronize these signaling pathways and their mechanisms during cellular migration remain largely unexplored. METHODS: miR-29a-3p was exogenously expressed in either wild-type or DiGeorge syndrome critical region 8 (DGCR8) knockdown hMSCs. Multiple pathway components were analyzed using Western blotting, immunohistochemistry, and real-time quantitative PCR. hMSC migration was assessed both in vitro and in vivo through wound healing, Transwell, contraction, and in vivo migration assays. Extensive bioinformatic analyses using gene set enrichment analysis and Ingenuity pathway analysis identified enriched pathways, upstream regulators, and downstream targets. RESULTS: The global depletion of microRNAs (miRNAs) due to DGCR8 gene silencing, a critical component of miRNA biogenesis, significantly impaired hMSC migration. The bioinformatics analysis identified miR-29a-3p as a pivotal upstream regulator. Its overexpression in DGCR8-knockdown hMSCs markedly improved their migration capabilities. Our data demonstrate that miR-29a-3p enhances cell migration by directly inhibiting two key phosphatases: protein tyrosine phosphatase receptor type kappa (PTPRK) and phosphatase and tensin homolog (PTEN). The ectopic expression of miR-29a-3p stabilized the polarization of the Golgi apparatus and actin cytoskeleton during wound healing. It also altered actomyosin contractility and cellular traction forces by changing the distribution and phosphorylation of myosin light chain 2. Additionally, it regulated focal adhesions by modulating the levels of PTPRK and paxillin. In immunocompromised mice, the migration of hMSCs overexpressing miR-29a-3p toward a chemoattractant significantly increased. CONCLUSIONS: Our findings identify miR-29a-3p as a key upstream regulator that governs hMSC migration. Specifically, it was found to modulate principal signaling pathways, including polarization, actin cytoskeleton, contractility, and adhesion, both in vitro and in vivo, thereby reinforcing migration regulatory circuits.
Asunto(s)
Movimiento Celular , Células Madre Mesenquimatosas , MicroARNs , Transducción de Señal , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Movimiento Celular/genética , Transducción de Señal/genética , Animales , RatonesRESUMEN
The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG (curdlan-SKG) mice compared to the respective controls. Under hypoxic conditions in which HIF1A was stabilized, human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23, an upstream type 3 immunity-related cytokine. Similar to MIF, systemic overexpression of IL-23 induced SpA pathology in SKG mice, while the injection of a HIF1A-selective inhibitor (PX-478) into curdlan-SKG mice prevented or attenuated SpA pathology, as indicated by a marked reduction in the expression of MIF and IL-23. Furthermore, genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF, despite the presence of psoriasis-like dermatitis and blepharitis. We also found that MIF- and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice. These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification. Together, these results provide supporting evidence for an MIF/HIF1A regulatory network, and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.
Asunto(s)
Condrogénesis , Modelos Animales de Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia , Factores Inhibidores de la Migración de Macrófagos , Neutrófilos , Animales , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Factores Inhibidores de la Migración de Macrófagos/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neutrófilos/inmunología , Neutrófilos/metabolismo , Humanos , Ratones , Espondiloartritis/inmunología , Espondiloartritis/patología , Oxidorreductasas Intramoleculares/metabolismo , Oxidorreductasas Intramoleculares/genética , Interleucina-23/metabolismo , beta-Glucanos/farmacología , Ratones Endogámicos C57BL , Masculino , Femenino , InmunidadRESUMEN
The redox regulation, maintaining a balance between oxidation and reduction in living cells, is vital for cellular homeostasis, intricate signaling networks, and appropriate responses to physiological and environmental cues. Here, a novel redox sensor, based on DNA-encapsulated silver nanoclusters (DNA/AgNCs) and well-defined chemical fluorophores, effectively illustrating cellular redox states in live cells is introduced. Among various i-motif DNAs, the photophysical property of poly-cytosines (C20)-encapsulated AgNCs that sense reactive oxygen species (ROS) is adopted. However, the sensitivity of C20/AgNCs is insufficient for evaluating ROS levels in live cells. To overcome this drawback, the ROS sensing mechanism of C20/AgNCs through gel electrophoresis, mass spectrometry, and small-angle X-ray scattering is primarily defined. Then, by tethering fluorescein amidite (FAM) and Cyanine 5 (Cy5) dyes to each end of the C20/AgNCs sensor, an Energy Transfer (ET) between AgNCs and FAM is achieved, resulting in intensified green fluorescence upon ROS detection. Taken together, the FAM-C20/AgNCs-Cy5 redox sensor enables dynamic visualization of intracellular redox states, yielding insights into oxidative stress-related processes in live cells.
RESUMEN
OBJECTIVE: Upadacitinib improved the signs and symptoms of non-radiographic axial spondyloarthritis (nr-axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT-AXIS 2 nr-axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr-axSpA in SELECT-AXIS 2. METHODS: Patients aged at least 18 years diagnosed with nr-axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52-week double-blind period. Efficacy was assessed using non-responder imputation incorporating multiple imputation (NRI-MI) and as-observed analyses for binary endpoints, and mixed-effects model repeated measures for continuous endpoints. RESULTS: Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI-MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI-MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. CONCLUSION: Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit-risk profile of upadacitinib treatment for nr-axSpA.
RESUMEN
BACKGROUND: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage. METHODS: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method. RESULTS: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias. CONCLUSIONS: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.
Asunto(s)
Espondiloartritis , Inhibidores del Factor de Necrosis Tumoral , Humanos , Espondiloartritis/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Brote de los Síntomas , Reducción Gradual de Medicamentos , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.
Asunto(s)
Cistectomía , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Fumar , Neoplasias de la Vejiga Urinaria , Humanos , Cistectomía/efectos adversos , Cistectomía/métodos , Masculino , Femenino , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Anciano , Fumar/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Bases de Datos Factuales , Resultado del Tratamiento , República de Corea/epidemiología , Periodo PreoperatorioRESUMEN
In this study, we investigated the trimerization mechanism and structure of heat shock factor 1 (HSF1) using western blotting, tryptophan (Trp) fluorescence spectroscopy, and molecular modeling. First, we examined the DNA-binding domains of human (Homo sapiens), goldfish (Carassius auratus), and walleye pollock (Gadus chalcogrammus) HSF1s by mutating key residues (36 and 103) that are thought to directly affect trimer formation. Human, goldfish, and walleye pollock HSF1s contain cysteine at residue 36 but cysteine (C), tyrosine (Y), and phenylalanine (F), respectively, at residue 103. The optimal trimerization temperatures for the wild-type HSF1s of each species were found to be 42, 37, and 20 °C, respectively. Interestingly, a mutation experiment revealed that trimerization occurred at 42 °C when residue 103 was cysteine, at 37 °C when it was tyrosine, and at 20 °C when it was phenylalanine, regardless of the species. In addition, it was confirmed that when residue 103 of the three species was mutated to alanine, trimerization did not occur. This suggests that in addition to trimerization via disulfide bond formation between the cysteine residues in human HSF1, trimerization can also occur via the formation of a different type of bond between cysteine and aromatic ring residues such as tyrosine and phenylalanine. We also confirmed that at least one cysteine is required for the trimerization of HSF1s, regardless of its position (residue 36 or 103). Additionally, it was shown that the trimer formation temperature is related to growth and survival in fish.
Asunto(s)
Aminoácidos Aromáticos , Cisteína , Factores de Transcripción del Choque Térmico , Animales , Humanos , Aminoácidos Aromáticos/metabolismo , Aminoácidos Aromáticos/química , Cisteína/química , Cisteína/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Carpa Dorada/metabolismo , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/química , Factores de Transcripción del Choque Térmico/genética , Modelos Moleculares , Dominios Proteicos , Multimerización de ProteínaRESUMEN
The present study aimed to assess the efficiency of zeolite in mitigating the nitrogen (N) losses through ammonia (NH3) and nitrous oxide (N2O) emissions from pig slurry (PS) applied to Italian ryegrass (IRG)-maize fields under a crop rotation system and the consequent effect on nitrogen use efficiency (NUE) for forage production. PS was applied at rates of 150 and 200 kg N ha-1 for the IRG and maize growing seasons, respectively, with or without zeolite. Soil mineral N content and NH3 and N2O emissions were measured periodically throughout the year-round cultivation of IRG and maize. Forage yield and nutritional composition were also analyzed at the harvest time of each crop. The PS with/without zeolite application effects were interpreted by comparison with those obtained for the negative control (no-N fertilization). Soil ammonium (NH4+) content in the PS-applied plots sharply increased within the first week, then progressively decreased in both the IRG and maize growing seasons. Soil NH4+ contents in the zeolite-amended plots were higher compared to the treatment without zeolite except for the first 1 or 2 weeks after PS application when soil nitrate (NO3-) contents significantly decreased. The increase in soil NH4+ content as affected by zeolite application was more distinct in the maize growing season than in the IRG growing season. NH3 emission was predominant at the early 2 weeks after PS application. Zeolite application reduced the cumulative emission of NH3 from PS by 16.7% and 24.4% and that of N2O by 15.6% and 31.5% in the IRG growing and maize growing seasons, respectively. NUE for dry matter (DM) and total digestible nutrients (TDN) production significantly improved in annual yield basis of the IRG-maize cropping. Zeolite application in PS-applied field may represent effective management in mitigating N losses through odorous NH3 and greenhouse gas (N2O) emissions, thereby improving NUE forage production.
Asunto(s)
Lolium , Zeolitas , Animales , Porcinos , Nitrógeno , Zea mays , Suelo , Óxido Nitroso/análisis , Fertilizantes , Producción de Cultivos , Italia , AgriculturaRESUMEN
Objective: Ankylosing spondylitis (AS) is chronic inflammatory arthritis causing structural damage and radiographic progression to the spine due to repeated and continuous inflammation over a long period. This study establishes the application of machine learning models to predict radiographic progression in AS patients using time-series data from electronic medical records (EMRs). Methods: EMR data, including baseline characteristics, laboratory findings, drug administration, and modified Stoke AS Spine Score (mSASSS), were collected from 1,123 AS patients between January 2001 and December 2018 at a single center at the time of first (T1), second (T2), and third (T3) visits. The radiographic progression of the (n+1)th visit (Pn+1=(mSASSSn+1-mSASSSn)/(Tn+1-Tn)≥1 unit per year) was predicted using follow-up visit datasets from T1 to Tn. We used three machine learning methods (logistic regression with the least absolute shrinkage and selection operation, random forest, and extreme gradient boosting algorithms) with three-fold cross-validation. Results: The random forest model using the T1 EMR dataset best predicted the radiographic progression P2 among the machine learning models tested with a mean accuracy and area under the curves of 73.73% and 0.79, respectively. Among the T1 variables, the most important variables for predicting radiographic progression were in the order of total mSASSS, age, and alkaline phosphatase. Conclusion: Prognosis predictive models using time-series data showed reasonable performance with clinical features of the first visit dataset when predicting radiographic progression.
RESUMEN
BACKGROUND: Microbial imbalance in the gut from antibiotic use may be an etiologic factor of Kawasaki disease (KD). We aimed to identify the association between the use of antibiotics and the development of KD, considering various antibiotic profiles. METHODS: A population-based, case-control study was performed using data from the Health Insurance Review and Assessment Service database. Children <5 years of age, who were diagnosed with KD between 2016 and 2019, were identified. Propensity score-matched controls were selected from the general population in a 1:5 ratio. Four separate study cohorts were created according to different periods of antibiotic use: (1) within 28 days and (2) 12 months after birth and (3) within 6 months and (4) 12 months from the index date. Profiles regarding antibiotic use were compared between patients with KD and matched controls. RESULTS: We included 17,818 patients with KD and 89,090 matched controls. Use of antibiotics within 6 months [odds ratio (OR): 1.18; 95% confidence interval (CI): 1.12-1.26] and 12 months (OR: 1.23; 95% CI: 1.14-1.32) from the index date were associated with the development of KD. The association between antibiotic use and KD was most prominent in patients who had received 3 or more types of antibiotics within 12 months from the index date (OR: 1.26; 95% CI: 1.17-1.37). CONCLUSIONS: Antibiotic use within the preceding 6 or 12 months was associated with KD. Alteration in gut microbiota due to antibiotic usage might play a role in the development of KD.
Asunto(s)
Antibacterianos , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/epidemiología , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Masculino , Lactante , Preescolar , Estudios de Casos y Controles , Femenino , Estudios de Cohortes , Recién Nacido , Microbioma Gastrointestinal/efectos de los fármacos , Factores de Riesgo , Puntaje de PropensiónRESUMEN
Nonradiographic axial spondyloarthritis (nr-axSpA) is a subtype of SpA with undeveloped definite radiographic sacroiliitis. Tumor necrosis factor inhibitors have demonstrated effectiveness in nr-axSpA patients who do not respond to first-line therapy. More recently, accumulated data from genetic, experimental, and clinical studies revealed that IL-17 is a key player in the pathogenesis of SpA, leading to development of new biologics directly inhibiting IL-17. Among them, ixekizumab is a high-affinity monoclonal antibody that selectively targets IL-17A and has exhibited significant efficacy and acceptable safety profiles in the treatment of nr-axSpA. The aim of this paper is to narratively review the recent insights of IL-17 in the pathogenesis of axSpA and discuss the effectiveness and safety of ixekizumab in treatment of nr-axSpA.
Nonradiographic axial spondyloarthritis (Nr-axSpA) is a type of inflammatory disease affecting the spine, particularly the sacroiliac joints, where x-rays don't clearly show signs of damage. When initial treatments don't work, medications like tumor necrosis factor inhibitors can help. But now, recent studies have found that IL-17 plays a big role in this condition. Because of this, new drugs targeting IL-17, such as ixekizumab, have been developed. Ixekizumab is a powerful medication that specifically targets IL-17A. Studies have found it to be both effective and safe in treating nr-axSpA. This article aims to explain how IL-17 contributes to this condition and discuss how ixekizumab can help people with nr-axSpA.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Interleucina-17 , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Interleucina-17/antagonistas & inhibidores , Interleucina-17/metabolismo , Espondiloartritis Axial/tratamiento farmacológico , Animales , Resultado del TratamientoRESUMEN
PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.
Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
Tailoring the optical properties of metamaterials is crucial for improving the performance of infrared (IR) applications. Generally, IR camouflage materials are required to have low IR-emission properties for the detected bands (3-5 and 8-12 µm), in which IR detection is accomplished. However, the heat residue by suppressed thermal radiation degrades the thermal dissipation capacity and thermal stability of IR camouflage materials. Herein, a multilayer metal-dielectric-metal (MDM) selective emitter with high IR-emission performance in the undetected band for thermal management and low IR-emission performance in the detected band for IR camouflage is introduced. Compared to a conventional selective emitter and a low-emission material (Au film), the multiresonance selective emitter exhibited 125 and 2910% increases in heat dissipation within the undetected band, respectively. In addition, the proposed camouflage material exhibited a substantial reduction in emissive energy within the detected bands of 3-5 and 8-12 µm, with reductions of 72 and 83%, respectively, compared to that of a high-emission surface. The effectiveness of our IR camouflage was demonstrated by IR camera measurements. When the surface temperature was 360 K, the radiance temperatures of the multilayer multipeak selective emitter were 314 and 309 K for the 3-5 and 8-12 µm bands, respectively. Thermal management experiments demonstrated the enhanced thermal stability of the multiresonance selective emitter, especially in conditions of low pressure and high heat flux, when compared to that of the low-emissivity film. This work provides a practical strategy to enhance the thermal emission of a selective emitter, expanding its potential beyond IR camouflage to various energy applications.