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1.
J Neurosurg Case Lessons ; 8(6)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39102750

RESUMEN

BACKGROUND: Cauda equina neuroendocrine tumors (CENETs), previously known as cauda equina paragangliomas, and multiple cerebral cavernous malformations (CCMs) are uncommon conditions affecting the central nervous system. To the authors' knowledge, they have not been reported in the same patient. OBSERVATIONS: The authors present the case of a 45-year-old male with CENET and concurrent incidental MRI findings of multiple CCMs. Familial CCMs are associated with mutations in the KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) genes. Peripheral paragangliomas have been associated with mutations in succinate dehydrogenase (SDHx), RET (multiple endocrine neoplasia 2), VHL (von Hippel-Lindau syndrome), and NF1 (neurofibromatosis type 1) genes. Except for a single case, cauda equina paragangliomas have not been associated with any underlying genetic mutations. LESSONS: It is unclear whether the co-occurrence of these two rare conditions in the same patient is coincidental or suggests a possible shared pathogenesis. https://thejns.org/doi/10.3171/CASE24102.

2.
Oncologist ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39173023

RESUMEN

BACKGROUND: Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)-altered cholangiocarcinoma (CCA) in the FIGHT-202 trial. However, limited real-world evidence exists on treatment patterns and outcomes in this setting. PATIENTS AND METHODS: Patient characteristics, treatment patterns, and outcomes of US adults who received pemigatinib for unresectable, locally advanced or metastatic CCA were collected via retrospective physician-abstracted chart review. Results were summarized using descriptive statistics. RESULTS: Data from 120 patients (49.2% male; 55.0% White; 19.2% Hispanic; median age at initial pemigatinib prescription, 64.5 years) were collected from 18 physicians/practices. At the time of prescribing, 90.0% of patients had metastatic disease. FGFR2 testing was completed for 92.5% of patients; of those, all but one (result unknown) tested positive, and 95.5% were tested using next-generation sequencing. Pemigatinib was prescribed as second- and third-line therapy among 94.2% and 5.8% of patients, respectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day cycles (87.5% of patients). Among 60 patients (50.0% of the full cohort) who discontinued pemigatinib during the 6.5-month median study follow-up period, 68.3% discontinued due to disease progression. The median real-world progression-free survival (rwPFS) from the date of pemigatinib initiation was 7.4 months (95% CI: 6.4-8.6), and the real-world overall response rate (rwORR) was 59.2% (95% CI: 50.0%-68.4%). CONCLUSION: This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under real-world conditions. Findings support the clinical benefit of pemigatinib demonstrated in FIGHT-202.

3.
J Nanobiotechnology ; 22(1): 476, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135064

RESUMEN

BACKGROUND: Current needle-based vaccination for respiratory viruses is ineffective at producing sufficient, long-lasting local immunity in the elderly. Direct pulmonary delivery to the resident local pulmonary immune cells can create long-term mucosal responses. However, criteria for drug vehicle design rules that can overcome age-specific changes in immune cell functions have yet to be established. RESULTS: Here, in vivo charge-based nanoparticle (NP) uptake was compared in mice of two age groups (2- and 16-months) within the four notable pulmonary antigen presenting cell (APC) populations: alveolar macrophages (AM), interstitial macrophages (IM), CD103+ dendritic cells (DCs), and CD11b+ DCs. Both macrophage populations exhibited preferential uptake of anionic nanoparticles but showed inverse rates of phagocytosis between the AM and IM populations across age. DC populations demonstrated preferential uptake of cationic nanoparticles, which remarkably did not significantly change in the aged group. Further characterization of cell phenotypes post-NP internalization demonstrated unique surface marker expression and activation levels for each APC population, showcasing heightened DC inflammatory response to NP delivery in the aged group. CONCLUSION: The age of mice demonstrated significant preferences in the charge-based NP uptake in APCs that differed greatly between macrophages and DCs. Carefully balance of the targeting and activation of specific types of pulmonary APCs will be critical to produce efficient, age-based vaccines for the growing elderly population.


Asunto(s)
Células Presentadoras de Antígenos , Células Dendríticas , Pulmón , Ratones Endogámicos C57BL , Nanopartículas , Fagocitosis , Animales , Nanopartículas/química , Ratones , Pulmón/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Presentadoras de Antígenos/inmunología , Macrófagos Alveolares/metabolismo , Polietilenglicoles/química , Envejecimiento , Femenino , Factores de Edad
4.
MicroPubl Biol ; 20242024.
Artículo en Inglés | MEDLINE | ID: mdl-39144098

RESUMEN

The collagen-based epidermal 'cuticle' of Caenorhabditis elegans functions as an extracellular sensor for damage that regulates genes promoting osmotic balance, innate immunity, and detoxification. Prior studies demonstrate that SKN-1 , an ortholog of the mammalian Nrf transcription factors, activates core detoxification genes downstream from cuticle damage. Prior RNAseq data suggested that expression of five genes with functions in redox balance, ATP homeostasis, and lysosome function ( gst-15 , gst-24 , cyts-1 , argk-1 , and mfsd-8.4 ) were increased in a cuticle collagen mutant; this study employed RT-qPCR to verify this observation and to test the role of SKN-1 . Activation of all five genes was verified in dpy-7 mutants, but none were reduced by skn-1 (RNAi) suggesting parallel or distinct regulatory mechanisms.

5.
Int J Mol Sci ; 25(14)2024 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-39063198

RESUMEN

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau (MAPT) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.


Asunto(s)
Moléculas de Adhesión Celular Neuronal , Inmunoglobulina G , Humanos , Moléculas de Adhesión Celular Neuronal/inmunología , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Tauopatías/inmunología , Tauopatías/genética , Tauopatías/metabolismo , Animales , Proteínas tau/inmunología , Proteínas tau/metabolismo , Proteínas tau/genética , Autoanticuerpos/inmunología
6.
Sci Rep ; 14(1): 15596, 2024 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971939

RESUMEN

Common beans (CB), a vital source for high protein content, plays a crucial role in ensuring both nutrition and economic stability in diverse communities, particularly in Africa and Latin America. However, CB cultivation poses a significant threat to diseases that can drastically reduce yield and quality. Detecting these diseases solely based on visual symptoms is challenging, due to the variability across different pathogens and similar symptoms caused by distinct pathogens, further complicating the detection process. Traditional methods relying solely on farmers' ability to detect diseases is inadequate, and while engaging expert pathologists and advanced laboratories is necessary, it can also be resource intensive. To address this challenge, we present a AI-driven system for rapid and cost-effective CB disease detection, leveraging state-of-the-art deep learning and object detection technologies. We utilized an extensive image dataset collected from disease hotspots in Africa and Colombia, focusing on five major diseases: Angular Leaf Spot (ALS), Common Bacterial Blight (CBB), Common Bean Mosaic Virus (CBMV), Bean Rust, and Anthracnose, covering both leaf and pod samples in real-field settings. However, pod images are only available for Angular Leaf Spot disease. The study employed data augmentation techniques and annotation at both whole and micro levels for comprehensive analysis. To train the model, we utilized three advanced YOLO architectures: YOLOv7, YOLOv8, and YOLO-NAS. Particularly for whole leaf annotations, the YOLO-NAS model achieves the highest mAP value of up to 97.9% and a recall of 98.8%, indicating superior detection accuracy. In contrast, for whole pod disease detection, YOLOv7 and YOLOv8 outperformed YOLO-NAS, with mAP values exceeding 95% and 93% recall. However, micro annotation consistently yields lower performance than whole annotation across all disease classes and plant parts, as examined by all YOLO models, highlighting an unexpected discrepancy in detection accuracy. Furthermore, we successfully deployed YOLO-NAS annotation models into an Android app, validating their effectiveness on unseen data from disease hotspots with high classification accuracy (90%). This accomplishment showcases the integration of deep learning into our production pipeline, a process known as DLOps. This innovative approach significantly reduces diagnosis time, enabling farmers to take prompt management interventions. The potential benefits extend beyond rapid diagnosis serving as an early warning system to enhance common bean productivity and quality.


Asunto(s)
Aprendizaje Profundo , Phaseolus , Enfermedades de las Plantas , Phaseolus/virología , Phaseolus/microbiología , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/microbiología , Agricultura/métodos , Hojas de la Planta/virología , Hojas de la Planta/microbiología , África , Colombia
7.
Sci Rep ; 14(1): 17515, 2024 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080319

RESUMEN

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 receptor with high affinity (KD: 7.1 pM). In human cells, JNJ-77242113 potently and selectively inhibited proximal IL-23 signaling (IC50: 5.6 pM) without impacting IL-12 signaling. JNJ-77242113 inhibited IL-23-induced interferon (IFN)γ production in NK cells, and in blood from healthy donors and psoriasis patients (IC50: 18.4, 11 and 9 pM, respectively). In a rat trinitrobenzene sulfonic acid-induced colitis model, oral JNJ-77242113 attenuated disease parameters at doses ≥ 0.3 mg/kg/day. Pharmacologic activity beyond the gastrointestinal tract was also demonstrated. In blood from rats receiving oral JNJ-77242113, dose-dependent inhibition of ex vivo IL-23-stimulated IL-17A production was observed. In an IL-23-induced rat skin inflammation model, JNJ-77242113 inhibited IL-23-induced skin thickening and IL-17A, -17F and -22 gene induction. Oral dosing of JNJ-77242113 in healthy human volunteers inhibited ex vivo IL-23-stimulated IFNγ production in whole blood. Thus, JNJ-77242113 provided selective, systemic IL-23 pathway inhibition in preclinical models which translated to pharmacodynamic activity in healthy human volunteers, supporting the potential for JNJ-77242113 as a selective oral therapy for IL-23-driven immune-mediated diseases.


Asunto(s)
Interleucina-23 , Receptores de Interleucina , Animales , Humanos , Ratas , Interleucina-23/metabolismo , Administración Oral , Receptores de Interleucina/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Modelos Animales de Enfermedad , Péptidos/farmacología , Péptidos/administración & dosificación , Femenino , Ratas Sprague-Dawley
8.
J Am Board Fam Med ; 36(6): 933-941, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38171582

RESUMEN

INTRODUCTION: Academic detailing, patient-panel management, and mailed, stool-based testing have each been utilized to increase colorectal cancer (CRC) screening in rural clinics. The effectiveness of combining these interventions to increase CRC screening during COVID-19 restrictions was unclear. METHODS: We explored the effects of a multi-component intervention including academic detailing, active patient panel management, and mailed MT-sDNA testing on colorectal cancer screening in our rural family medicine clinic. Baseline interventions included EMR-based provider alerts and mailed patient reminders. Our intervention (March-May 2020) and follow-up periods (June-August 2020) coincided with the initial COVID-19 surge, giving us the opportunity to observe the effects of our intervention during COVID-19 restrictions. RESULTS: A total of 407 patients were eligible and overdue for colorectal cancer screening. Our clinic's CRC screening rate increased significantly after intervention (69.7%) as compared with before (64.3%) (P = <0.01; 95%CI = 5.39-5.4). Our clinic's CRC screening rates increased significantly during the initial 3 months of the COVID-19 surge (67.8%) compared with the same period the prior year. (62.3%) (P = .003; 95%CI = 3.4-7.6). Our CRC screening rates increased after intervention (69.7%) compared with our regional health system (67%) (P = <0.01; 95%CI = 2.6-2.77). Our weekly stool-based CRC screening increased (94% increase) compared with other health systems nationally (61 to 83% decrease). DISCUSSION: A multi-component intervention, including academic detailing, panel management, and mailed MT-sDNA testing, can lead to significant increases in CRC screening in a rural family medicine clinic, empowering providers to maintain an effective CRC screening outreach during COVID-19 related restrictions.


Asunto(s)
COVID-19 , Neoplasias Colorrectales , Humanos , Detección Precoz del Cáncer , Servicios Postales , Neoplasias Colorrectales/diagnóstico , Sangre Oculta , ADN , COVID-19/diagnóstico , COVID-19/epidemiología , Tamizaje Masivo
9.
J Neurosci Methods ; 402: 110025, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38036185

RESUMEN

BACKGROUND: Immunohistochemical upregulation of glial fibrillary acidic protein (GFAP) is commonly used to detect astrogliosis in tissue sections and includes measurement of intensity and/or distribution of staining. There remains a lack of standard objective measures when diagnosing astrogliosis and its severity. NEW METHOD: Aim was to test a novel semi-quantitative assessment of GFAP which we term reactivity (R)-score, on its reproducibility and sensitivity to measure astrogliosis. The R-score, which is based on the proportion of astrocytes seen at each level of reactivity, was compared to 3 other commonly employed quantification methods in research: (1) thresholding, (2) point-counting, and (3) qualitative grading. Sub-regions of the hippocampus, medulla, and cerebellum were studied in piglet, and 4 human cases with clinically reported astrogliosis. Intra-assay coefficient of variation (CV) and percentage agreement cut-offs of ≤ 20% and ≥ 75% were used respectively to compare amongst the methods, with outcome measures being reproducibility across serial and non-serial sections, resilience to changes in experimental conditions, and inter- and intra-rater concordance. RESULTS: Averaged across 3 brain regions, the intra-assay coefficient of variation (CV) was 5% for R-score, with inter and intra-rater kappa scores being 0.99 and 0.95 respectively. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: Based on CV values, the R-score was superior to thresholding (CV of 51%) and point-counting (CV of 16%), with the qualitative grade being found to be on par (percentage agreement 95%). Given the ease, reproducibility and selectivity of the R-score, we propose its validity in future research purposes and clinical application.


Asunto(s)
Encéfalo , Gliosis , Animales , Humanos , Porcinos , Gliosis/metabolismo , Inmunohistoquímica , Proteína Ácida Fibrilar de la Glía/metabolismo , Reproducibilidad de los Resultados , Encéfalo/metabolismo , Astrocitos/metabolismo
10.
Phys Chem Chem Phys ; 26(1): 209-218, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38054255

RESUMEN

f-Block chemistry offers an opportunity to test current knowledge of chemical reactivity. The energy dependence of lanthanide cation (Ln+ = Ce+, Pr+, Nd+-Eu+) and actinide cation (An+ = Th+, U+-Am+) oxidation reactions by CO2, was observed by inductively coupled plasma tandem mass spectrometry. This reaction is commonly spin-unallowed because the neutral reactant (CO2, 1Σ+g) and product (CO, 1Σ+) require the metal and metal oxide cations to have the same spin state. Correlation of the promotion energy (Ep) to the first state with two free d-electrons with the reaction efficiency indicates that spin conservation is not a primary factor in the reaction rate. The Ep likely influences the reaction rate by partially setting the crossing between the ground and reactive states. Comparison of Ln+ and An+ congener reactivity indicates that the 5f-orbitals play a small role in the An+ reactions.

11.
Food Chem X ; 20: 101040, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38144842

RESUMEN

Given rising traders and consumers concerns, the global food industry is increasingly demanding authentic and traceable products. Consequently, there is a heightened focus on verifying geographical authenticity as food quality assurance. In this work, we assessed pattern recognition approaches based on elemental predictors to discern the provenance of mandarin juices from three distinct citrus-producing zones located in the Northeast region of Argentina. A total of 202 samples originating from two cultivars were prepared through microwave-assisted acid digestion and analyzed by microwave plasma atomic emission spectroscopy (MP-AES). Later, we applied linear discriminant analysis (LDA), k-nearest neighbor (k-NN), support vector machine (SVM), and random forest (RF) to the element data obtained. SVM accomplished the best classification performance with a 95.1% success rate, for which it was selected for citrus samples authentication. The proposed method highlights the capability of mineral profiles in accurately identifying the genuine origin of mandarin juices. By implementing this model in the food supply chain, it can prevent mislabeling fraud, thereby contributing to consumer protection.

12.
Emerg Infect Dis ; 29(12): 2482-2487, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37987582

RESUMEN

Avian paramyxovirus type 1 (APMV-1) is a virus of birds that results in a range of outcomes, from asymptomatic infections to outbreaks of systemic respiratory and neurologic disease, depending on the virus strain and the avian species affected. Humans are rarely affected; those who are predominantly experience mild conjunctivitis. We report a fatal case of neurologic disease in a 2-year-old immunocompromised child in Australia. Metagenomic sequencing and histopathology identified the causative agent as the pigeon variant of APMV-1. This diagnosis should be considered in neurologic conditions of undefined etiologies. Agnostic metagenomic sequencing methods are useful in such settings to direct diagnostic and therapeutic efforts.


Asunto(s)
Enfermedades Transmisibles , Enfermedad de Newcastle , Animales , Preescolar , Humanos , Australia/epidemiología , Columbidae , Enfermedad de Newcastle/epidemiología , Enfermedad de Newcastle/patología , Virus de la Enfermedad de Newcastle , Filogenia
13.
Waste Manag ; 171: 411-420, 2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37783136

RESUMEN

Digestion of waste feedstocks by larvae of the black soldier fly Hermetia illucens (Diptera: Stratiomyidae) (BSF) results in proteins for animal feed and organic fertilizer with a reduced environmental footprint, but it can still have negative environmental effects through greenhouse gas (GHG) and ammonia (NH3) emissions. Both biomass conversion by BSF larvae and associated GHG and NH3 emissions can depend on substrate properties that may be optimized through microbial inoculation pre-treatments, such as bokashi fermentation. Here, we quantified the effects of bokashi fermentation of brewery's spent grains on BSF rearing metrics and associated GHG and NH3 emissions at benchtop scale. We found that bokashi fermentation increased larval biomass by 40% and shortened development time by over two days on average, compared with unfermented spent grains. In line with increased larval growth, CO2 emissions in BSF larvae treatments were 31.0 and 79.0% higher in the bokashi fermented spent grains and Gainesville substrates, respectively, compared to the unfermented spent grains. Adding BSF larvae to the spent grains increased cumulative N2O emissions up to 64.0 mg N2O kg substratedry-1 but there were essentially no N2O emissions when larvae were added to fermented spent grains. Bokashi fermentation also reduced NH3 fluxes from the volatilization of substrate nitrogen in the BSF larvae treatment by 83.7-85.8% during days 7 and 9, possibly by increasing N assimilation by larvae or by reducing the transformation of substrate NH4+ to NH3. Therefore, bokashi fermentation may be applied to improve performance of BSF larvae on a common industrial waste stream and reduce associated emissions.

14.
Eur J Pharm Sci ; 191: 106596, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37770004

RESUMEN

Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic pulmonary fibrosis, and respiratory syncytial virus among others. Pulmonary therapeutics afford untapped potential for treating lung infection and disease through direct delivery to the site of action. However, the ability to innovate new therapeutic paradigms for respiratory diseases will rely on modeling the human lung microenvironment and including key cellular interactions that drive disease. One key feature of the lung microenvironment is the air-liquid interface (ALI). ALI interface modeling techniques, using cell-culture inserts, organoids, microfluidics, and precision lung slices (PCLS), are rapidly developing; however, one major component of these models is lacking-innate immune cell populations. Macrophages, neutrophils, and dendritic cells, among others, represent key lung cell populations, acting as the first responders during lung infection or injury. Innate immune cells respond to and modulate stromal cells and bridge the gap between the innate and adaptive immune system, controlling the bodies response to foreign pathogens and debris. In this article, we review the current state of ALI culture systems with a focus on innate immune cells and suggest ways to build on current models to add complexity and relevant immune cell populations.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Virus Sincitial Respiratorio Humano , Humanos , Pulmón , Macrófagos , Inmunidad , Inmunidad Innata
15.
Curr Issues Mol Biol ; 45(7): 5276-5292, 2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37504251

RESUMEN

Genomic alterations of CDKN2A and CDKN2B in astrocytomas have been an evolving area of study for decades. Most recently, there has been considerable interest in the effect of CDKN2A and/or CDKN2B (CDKN2A/B) homozygous deletions (HD) on the prognosis of isocitrate dehydrogenase (IDH)-mutant astrocytomas. This is highlighted by the adoption of CDKN2A/B HD as an essential criterion for astrocytoma and IDH-mutant central nervous system (CNS) WHO grade 4 in the fifth edition of the World Health Organisation (WHO) Classification of Central Nervous System Tumours (2021). The CDKN2A and CDKN2B genes are located on the short arm of chromosome 9. CDKN2A encodes for two proteins, p14 and p16, and CDKN2B encodes for p15. These proteins regulate cell growth and angiogenesis. Interpreting the impact of CDKN2A/B alterations on astrocytoma prognosis is complicated by recent changes in tumour classification and a lack of uniform standards for testing CDKN2A/B. While the prognostic impact of CDKN2A/B HD is established, the role of different CDKN2A/B alterations-heterozygous deletions (HeD), point mutations, and promoter methylation-is less clear. Consequently, how these alternations should be incorporated into patient management remains controversial. To this end, we reviewed the literature on different CDKN2A/B alterations in IDH-mutant astrocytomas and their impact on diagnosis and management. We also provided a historical review of the changing impact of CDKN2A/B alterations as glioma classification has evolved over time. Through this historical context, we demonstrate that CDKN2A/B HD is an important negative prognostic marker in IDH-mutant astrocytomas; however, the historical data is challenging to interpret given changes in tumour classification over time, variation in the quality of evidence, and variations in the techniques used to identify CDKN2A/B deletions. Therefore, future prospective studies using uniform classification and detection techniques are required to improve the clinical interpretation of this molecular marker.

16.
J Mol Diagn ; 25(10): 709-728, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37517472

RESUMEN

DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4%) and 213 of 269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74%) for 11b4, and 12 of 174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Metilación de ADN , Niño , Humanos , Australia , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Metilación de ADN/genética , Nueva Zelanda , Estudios Prospectivos , Reproducibilidad de los Resultados
17.
Food Chem X ; 18: 100744, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37397223

RESUMEN

This paper introduces a method for determining the authenticity of commercial cereal bars based on trace element fingerprints. In this regard, 120 cereal bars were prepared using microwave-assisted acid digestion and the concentrations of Al, Ba, Bi, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Se, Sn, Sr, V, and Zn were later measured by ICP-MS. Results confirmed the suitability of the analyzed samples for human consumption. Multielemental data underwent autoscaling preprocessing for then applying PCA, CART, and LDA to input data set. LDA model accomplished the highest classification modeling performance with a success rate of 92%, making it the suitable model for reliable cereal bar prediction. The proposed method demonstrates the potential of trace element fingerprints in distinguishing cereal bar samples according to their type (conventional and gluten-free) and principal ingredient (fruit, yogurt, chocolate), thereby contributing to global efforts for food authentication.

18.
PLoS One ; 18(5): e0285328, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37155688

RESUMEN

In epidermal tissues, extracellular matrices (ECMs) function as barriers between the organism and environment. Despite being at the interface with the environment, little is known about the role of animal barrier ECMs in sensing stress and communicating with cytoprotective gene pathways in neighboring cells. We and others have identified a putative damage sensor in the C. elegans cuticle that regulates osmotic, detoxification, and innate immune response genes. This pathway is associated with circumferential collagen bands called annular furrows; mutation or loss of furrow collagens causes constitutive activation of osmotic, detoxification, and innate immune response genes. Here, we performed a genome-wide RNAi screen for modulators of osmotic stress response gene gpdh-1 in a furrow collagen mutant strain. RNAi of six genes identified in this screen were tested under other conditions and for effects on other stress responses. The functions of these genes suggest negative feedback within osmolyte accumulation pathways and interactions with ATP homeostasis and protein synthesis. Loss of these gpdh-1 modulators had distinct effects on canonical detoxification and innate immune response genes.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Interferencia de ARN , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Retroalimentación , Matriz Extracelular/metabolismo , Colágeno/metabolismo
19.
Nanomaterials (Basel) ; 13(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37177048

RESUMEN

With the growing population, access to clean water is one of the 21st-century world's challenges. For this reason, different strategies to reduce pollutants in water using renewable energy sources should be exploited. Photocatalysts with extended visible light harvesting are an interesting route to degrade harmful molecules utilized in plastics, as is the case of Bisphenol A (BPA). This work uses a microwave-assisted route for the synthesis of two photocatalysts (BiOI and Bi2MoO6). Then, BiOI/Bi2MoO6 heterostructures of varied ratios were produced using the same synthetic routes. The BiOI/Bi2MoO6 with a flower-like shape exhibited high photocatalytic activity for BPA degradation compared to the individual BiOI and Bi2MoO6. The high photocatalytic activity was attributed to the matching electronic band structures and the interfacial contact between BiOI and Bi2MoO6, which could enhance the separation of photo-generated charges. Electrochemical, optical, structural, and chemical characterization demonstrated that it forms a BiOI/Bi2MoO6 p-n heterojunction. The free radical scavenging studies showed that superoxide radicals (O2•-) and holes (h+) were the main reactive species, while hydroxyl radical (•OH) generation was negligible during the photocatalytic degradation of BPA. The results can potentiate the application of the microwave synthesis of photocatalytic materials.

20.
Adv Drug Deliv Rev ; 199: 114831, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37100206

RESUMEN

Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular defenders, and accessing mucosal associated lymphoid tissue to redirect systemic adaptive and memory responses. In this review, we breakdown key inhalable immunoengineering strategies for chronic, genetic, and infection-based inflammatory pulmonary disorders, encompassing the historic use of immunomodulatory agents, the transition to biological inspired or derived treatments, and novel approaches of complexing these materials into drug delivery vehicles for enhanced release outcomes. Alongside a brief description of key immune targets, fundamentals of aerosol drug delivery, and preclinical pulmonary models for immune response, we survey recent advances of inhaled immunotherapy platforms, ranging from small molecules and biologics to particulates and cell therapies, as well as prophylactic vaccines. In each section, we address the formulation design constraints for aerosol delivery as well as advantages for each platform in driving desirable immune modifications. Finally, prospects of clinical translation and outlook for inhaled immune engineering are discussed.


Asunto(s)
Pulmón , Vacunas , Humanos , Aerosoles , Inmunoterapia , Sistemas de Liberación de Medicamentos
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