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1.
Dermatology ; : 1-18, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39378855

RESUMEN

INTRODUCTION: Pustular psoriasis is a rare and severe form of psoriasis characterized by sterile pustules on an erythematous background. The disease ranges from localized to generalized forms, with the latter being particularly life-threatening and recurrent. Understanding the genetic basis of pustular psoriasis, particularly IL36RN mutations, is crucial for developing better treatments. This study aims to determine the prevalence and types of IL36RN gene mutations and their relationship with clinical and paraclinical features in patients with pustular psoriasis in Can Tho City, Vietnam. METHODS: A cross-sectional study was conducted at Can Tho Dermatology Hospital involving 59 patients diagnosed with generalized pustular psoriasis (GPP) according to ERASPEN and Japanese Dermatological Association criteria. Data on demographic, clinical, and laboratory characteristics were collected. IL36RN gene mutations were identified through genomic DNA sequencing. Statistical analyses were performed to explore associations between IL36RN mutations and clinical features. RESULTS: The study included 59 participants, predominantly female (69.5%), with an average age of 39.12 years. A significant proportion (83.1%) had a history of psoriasis, with frequent recurrences (94.9%). The most common IL36RN mutation identified was p.Arg10ArgfsX1, present in 44.1% of patients. Other mutations included p.Pro76Leu (20.3%) and p.Arg102Trp (1.7%). Patients with IL36RN mutations were younger and had an earlier disease onset. Significant associations were found between IL36RN mutations and clinical features such as fever (OR = 11, p < 0.0001) and geographic tongue (OR = 14.67, p < 0.0001). CONCLUSION: Our study reveals a high prevalence of IL36RN mutations, particularly p.Arg10ArgfsX1, in Vietnamese pustular psoriasis patients, strongly associating these mutations with clinical features like fever and geographic tongue.

2.
Cardiovasc Diabetol ; 23(1): 357, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385193

RESUMEN

BACKGROUND: Most existing risk equations for predicting/stratifying individual diabetic kidney disease (DKD) risks were developed using relatively dated data from selective and homogeneous trial populations comprising predominately Caucasian type 2 diabetes (T2D) patients. We seek to adapt risk equations for prediction of DKD progression (microalbuminuria, macroalbuminuria, and renal failure) using empiric data from a real-world population with T2D in Taiwan. METHODS: Risk equations from three well-known simulation models: UKPDS-OM2, RECODe, and CHIME models, were adapted. Discrimination and calibration were determined using the area under the receiver operating characteristic curve (AUROC), a calibration plot (slope and intercept), and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was performed for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of risk equations to address risk variations among patients. RESULTS: The RECODe equations for microalbuminuria and macroalbuminuria showed moderate discrimination (AUROC: 0.62 and 0.76) but underestimated the event risks (calibration slope > 1). The CHIME equation had the best discrimination for renal failure (AUROCs from CHIME, UKPDS-OM2 and RECODe: 0.77, 0.60 and 0.64, respectively). All three equations overestimated renal failure risk (calibration slope < 1). After rigorous updating, the calibration slope/intercept of the recalibrated RECODe for predicting microalbuminuria (0.87/0.0459) and macroalbuminuria (1.10/0.0004) risks as well as the recalibrated CHIME equation for predicting renal failure risk (0.95/-0.0014) were improved. CONCLUSIONS: Risk equations for prediction of DKD progression in real-world Taiwanese T2D patients were established, which can be incorporated into a multi-state simulation model to project and differentiate individual DKD risks for supporting timely interventions and health economic research.


Asunto(s)
Albuminuria , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Progresión de la Enfermedad , Valor Predictivo de las Pruebas , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/epidemiología , Medición de Riesgo , Taiwán/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , Anciano , Reproducibilidad de los Resultados , Albuminuria/diagnóstico , Albuminuria/epidemiología , Pronóstico , Técnicas de Apoyo para la Decisión , Factores de Tiempo
4.
Nucleic Acids Res ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39329259

RESUMEN

Multiple testis-specific histone variants are involved in the dynamic chromatin transitions during spermatogenesis. H2B.W1 (previously called H2BFWT) is an H2B variant specific to primate testis with hitherto unclear functions, although its single-nucleotide polymorphisms (SNPs) are closely associated with male non-obstructive infertility. Here, we found that H2B.W1 is only expressed in the mid-late spermatogonia stages, and H2B.W1 nucleosomes are defined by a more flexible structure originating from weakened interactions between histones and DNA. Furthermore, one of its SNPs, H2B.W1-H100R, which is associated with infertility, further destabilizes the nucleosomes and increases the nucleosome unwrapping rate by interfering with the R100 and H4 K91/R92 interaction. Our results suggest that destabilizing H2B.W1 containing nucleosomes might change the chromatin structure of spermatogonia, and that H2B.W1-H100R enhances the nucleosome-destabilizing effects, leading to infertility.

5.
ACS Appl Mater Interfaces ; 16(39): 53195-53206, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39306766

RESUMEN

Ternary metal carbide TiAlC has been proposed as a metal gate material in logic semiconductor devices. It is a hard-to-etch material due to the low volatility of the etch byproducts. Here, a simple, highly controllable, and dry etching method for TiAlC has been first presented using nonhalogen N2/H2 plasmas at low pressure (several Pa) and 20 °C. A capacitively coupled plasma etcher was used to generate N2/H2 plasmas containing active species, such as N, NH, and H to modify the metal carbide surface. The etch rate of TiAlC was obtained at 3 nm/min by using the N2/H2 plasma, whereas no etching occurred with pure N2 plasma or pure H2 plasma under the same conditions. The surface roughness of the TiAlC film etched by N2/H2 plasma was controlled at the atomic level. A smooth etched surface was achieved with a root-mean-square roughness of 0.40 nm, comparable to the initial roughness of 0.44 nm. The plasma properties of the N2/H2 plasmas were diagnosed by using a high-resolution optical emission spectrometer, detecting the NH molecular line at 336 nm. The etching behavior and plasma-surface reaction between N2/H2 plasma and TiAlC were investigated by using in situ spectroscopic ellipsometry, in situ attenuated total reflectance-Fourier transform infrared spectrometry, and X-ray photoelectron spectroscopy. The findings indicate that the N-H, C-N, and Ti(Al)-N bonds form on the TiAlC surface etched by the N2/H2 plasmas. The mechanism for etching of TiAlC involving transformation reactions between inorganic materials (metal carbides) and inorganic etchants (N2/H2 plasma) to form volatile organic compounds such as methylated, methyl-aminated, and aminated metals is proposed. Nonhalogen or nonorganic compound etchants were used during the etching process. The study provides useful insights into microfabrication for large-scale integrated circuits.

6.
Plant Environ Interact ; 5(5): e70009, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39262832

RESUMEN

This study evaluates the phytotoxic potential of methanolic extracts from six Asteraceae species: Wedelia chinensis, Helianthus annuus, Cosmos bipinnatus, Tagetes erecta, Tithonia diversifolia, and Zinnia elegans. The extracts were tested at concentrations of 0.03, 0.1, 0.3, and 1.0 g/mL to assess their inhibitory effects on the radicle and hypocotyl lengths of Echinochloa crus-galli and Echinochloa colona. The two most potent species, C. bipinnatus and T. diversifolia, were further evaluated using extracts from their roots, stems, and leaves. Among these, C. bipinnatus leaf extracts showed the most significant phytotoxicity and were tested at 20, 40, and 60 days of plant age. At 0.03 g/mL, C. bipinnatus extract inhibited the hypocotyl and radicle lengths of E. colona by 23.01% and 56.45%, and E. crus-galli by 8.5% and 36.35%, respectively. At 1.0 g/mL, the extract inhibited the hypocotyl lengths of E. colona and E. crus-galli by 97.54% and 88.15%, and the radicle lengths by 93.52% and 99.99%, respectively. The 60-day-old C. bipinnatus leaf extract exhibited the highest inhibitory effect, correlating with the identification of key allelochemicals such as cinnamic acid, caffeic acid, coumaric acid, ferulic acid, 2-4 dimethohydroxy benzoic acid, and salicylic acid. These findings suggest that the 60-day-old C. bipinnatus leaf extracts have strong potential for use in the biological control of these weed species, offering a promising avenue for the development of natural herbicides.

7.
Food Chem ; 460(Pt 1): 140479, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39053271

RESUMEN

Heavy metals such as cadmium (Cd), arsenic (As), and lead (Pb) pose significant health risks, particularly in Asia, where rice is a staple for nearly three billion people. Despite their known dangers and environmental prevalence, studies addressing their concentrations in rice across different regions and the associated health implications remain insufficient. This review systematically examines the occurrence and impact of these toxic elements, filling a critical gap in the literature. Data from seven countries indicate mean concentrations in the order of Pb > As>Cd, with values of 0.255 ± 0.013, 0.236 ± 0.317, and 0.136 ± 0.150 mg/kg, respectively. Uncertainty analysis shows extensive variability, especially for Cd, with a 95% confidence interval range from 0.220 to 0.992 mg/kg. The typical daily intake of heavy metals through rice consumption, in the order of As>Cd > Pb, frequently exceeds safe limits. Generally, data obtained from various studies showed that children were more prone to heavy metal contamination through rice consumption than adults. This review is fundamental for ongoing monitoring, future research, and management strategies to reduce heavy metal contamination in rice.


Asunto(s)
Contaminación de Alimentos , Metales Pesados , Oryza , Oryza/química , Oryza/metabolismo , Humanos , Contaminación de Alimentos/análisis , Asia , Metales Pesados/análisis , Arsénico/análisis , Cadmio/análisis , Plomo/análisis
8.
J Ethnopharmacol ; 334: 118519, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38971340

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Vietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. AIM OF THE STUDY: The study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. METHODS: According to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. RESULTS: The assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 µM). CONCLUSION: The results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.


Asunto(s)
Antiinflamatorios , Antioxidantes , Artemisia , Edema , Extractos Vegetales , Xantina Oxidasa , Animales , Xantina Oxidasa/antagonistas & inhibidores , Xantina Oxidasa/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Ratones , Células RAW 264.7 , Edema/tratamiento farmacológico , Edema/inducido químicamente , Artemisia/química , Masculino , Ácido Úrico , Flavonoides/farmacología , Óxido Nítrico/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Carragenina
9.
Heliyon ; 10(12): e32536, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38975104

RESUMEN

Objective: The Bárány Society recently established diagnostic criteria for presbyvestibulopathy, an age-related bilateral vestibular impairments in older individuals. Drawing upon a cross-sectional database, this study delves into the demographic and clinical features of presbyvestibulopathy patients and investigates the implications of otolith dysfunction. Methods: The study retrospectively analyzed 1218 patients aged 60 years or older who visited the tertiary dizziness clinic in 2020, due to symptoms of dizziness or instability. By reviewing medical records, we gathered clinical information and laboratory vestibular test results, such as cervical and ocular vestibular evoked myogenic potentials, and subjective visual vertical. Results: Out of 1218 patients aged 60 and above who reported dizziness or unsteadiness, 33 patients (2.7 %, with an average age of 74.2 ± 9.2 years) were diagnosed with presbyvestibulopathy. Deficiencies in horizontal angular vestibulo-ocular reflex were found in caloric tests (75 %), video head impulse tests (51.7 %), and rotatory chair tests (47.8 %), respectively. Otolith dysfunction was also observed, as shown by abnormal ocular and cervical vestibular evoked myogenic potentials in 62.96 % and 51.85 % of patients, and abnormal subjective visual vertical in 45.8 % of the cases. Conclusions: Among elderly patients experiencing consistent dizziness or instability, the incidence of presbyvestibulopathy was approximately 2.7 % over one year. Alongside the abnormalities detected in the horizontal angular vestibulo-ocular reflex, significant changes were also noted in the ocular and cervical vestibular evoked myogenic potentials, as well as in the subjective visual vertical tests. As a result, it's vital to underscore the significance of both otolithic function and vestibulo-ocular reflex in the fundamental mechanisms of presbyvestibulopathy.

10.
BMC Genomics ; 25(1): 621, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898417

RESUMEN

BACKGROUND: Whole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide. RESULTS: Differential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45-52 days after planting, followed by roots initiated at 52-60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1. CONCLUSIONS: Our study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis.


Asunto(s)
Arabidopsis , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Herbicidas , Senescencia de la Planta , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Herbicidas/farmacología , Herbicidas/toxicidad , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Senescencia de la Planta/genética , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Transcriptoma , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
11.
Glob Health Sci Pract ; 12(3)2024 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-38936961

RESUMEN

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.


Asunto(s)
COVID-19 , Humanos , Vietnam/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/epidemiología , Tamizaje Masivo/organización & administración , Tamizaje Masivo/métodos , SARS-CoV-2 , Persona de Mediana Edad , Radiografía Torácica , Tuberculosis/diagnóstico , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Femenino , Pandemias , Masculino , Poblaciones Vulnerables
12.
Prog Mol Biol Transl Sci ; 207: 337-353, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38942543

RESUMEN

Regenerative medicine and cosmetics are currently two outstanding fields for drug discovery. Although many pharmaceutical products for regenerative medicine and cosmetics have received approval by official agencies, several challenges are still needed to overcome, especially financial and time issues. As a result, drug repositioning, which is the usage of previously approved drugs for new treatment, stands out as a promising approach to tackle these problems. Recently, increasing scientific evidence is collected to demonstrate the applicability of this novel method in the field of regenerative medicine and cosmetics. Experts in drug development have also taken advantage of novel technologies to discover new candidates for repositioning purposes following computational approach, one of two main approaches of drug repositioning. Therefore, numerous repurposed candidates have obtained approval to enter the market and have witnessed financial success such as minoxidil and fingolimod. The benefits of drug repositioning are undeniable for regenerative medicine and cosmetics. However, some aspects still need to be carefully considered regarding this method including actual effectiveness during clinical trials, patent regulations, data integration and analysis, publicly unavailable databases as well as environmental concerns and more effort are required to overcome these obstacles.


Asunto(s)
Cosméticos , Reposicionamiento de Medicamentos , Medicina Regenerativa , Medicina Regenerativa/economía , Humanos , Cosméticos/uso terapéutico , Cosméticos/economía , Animales
13.
Animals (Basel) ; 14(11)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38891635

RESUMEN

Prion diseases are fatal neurodegenerative disorders characterized by an accumulation of misfolded prion protein (PrPSc) in brain tissues. The shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is involved in prion disease progress. The interaction between Sho and PrP accelerates the PrPSc conversion rate while the SPRN gene polymorphisms have been associated with prion disease susceptibility in several species. Until now, the SPRN gene has not been investigated in ducks. We identified the duck SPRN gene sequence and investigated the genetic polymorphisms of 184 Pekin ducks. We compared the duck SPRN nucleotide sequence and the duck Sho protein amino acid sequence with those of several other species. Finally, we predicted the duck Sho protein structure and the effects of non-synonymous single nucleotide polymorphisms (SNPs) using computational programs. We were the first to report the Pekin duck SPRN gene sequence. The duck Sho protein sequence showed 100% identity compared with the chicken Sho protein sequence. We found 27 novel SNPs in the duck SPRN gene. Four amino acid substitutions were predicted to affect the hydrogen bond distribution in the duck Sho protein structure. Although MutPred2 and SNPs&GO predicted that all non-synonymous polymorphisms were neutral or benign, SIFT predicted that four variants, A22T, G49D, A68T, and M105I, were deleterious. To the best of our knowledge, this is the first report about the genetic and structural characteristics of the duck SPRN gene.

14.
Ther Adv Med Oncol ; 16: 17588359241242972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736554

RESUMEN

Background: Afatinib is indicated for advanced-stage non-small-cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) and uncommon mutations. However, real-world studies on this topic are limited. This study aimed to evaluate afatinib as first-line therapy for locally advanced and metastatic NSCLC with uncommon EGFR mutations. Patients and methods: A retrospective study included 92 patients with advanced NSCLC with uncommon and compound EGFR mutations, treated with afatinib as first-line therapy. Patients were followed up and evaluated every 3 months or when symptoms of progressive disease arose. The endpoints were objective response rate (ORR), time-to-treatment failure (TTF), and adverse events. Results: The G719X EGFR mutation had the highest occurrence rate (53.3% for both monotherapy and the compound). By contrast, the compound mutation G719X-S768I was observed at a rate of 22.8%. The ORR was 75%, with 15.2% of patients achieving complete response. The overall median TTF was 13.8 months. Patients with the G719X EGFR mutation (single and compound) had a median TTF of 19.3 months, longer than that of patients with other mutations, who had a median TTF of 11.2 months. Patients with compound EGFR mutations (G719X and S768I) demonstrated a median TTF of 23.2 months compared to that of 12.3 months for other mutations. Tolerated doses of 20 or 30 mg achieved a longer median TTF of 17.1 months compared to 11.2 months with 40 mg. Median TTF differed between patients with and without brain metastasis, at 11.2 and 16.9 months, respectively. Rash (55.4%) and diarrhea (53.3%) were the most common adverse events, primarily grades 1 and 2. Other side effects occurred at a low rate. Conclusion: Afatinib is effective for locally advanced metastatic NSCLC with uncommon EGFR mutations. Patients with G719X, compound G719X-S768I mutations, and tolerated doses of 20 or 30 mg had a longer median TTF than those with other mutations.

15.
Sci Rep ; 14(1): 9010, 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38637573

RESUMEN

Tubular injury is the most common cause of acute kidney injury. Histopathological diagnosis may help distinguish between the different types of acute kidney injury and aid in treatment. To date, a limited number of study has used deep-learning models to assist in the histopathological diagnosis of acute kidney injury. This study aimed to perform histopathological segmentation to identify the four structures of acute renal tubular injury using deep-learning models. A segmentation model was used to classify tubule-specific injuries following cisplatin treatment. A total of 45 whole-slide images with 400 generated patches were used in the segmentation model, and 27,478 annotations were created for four classes: glomerulus, healthy tubules, necrotic tubules, and tubules with casts. A segmentation model was developed using the DeepLabV3 architecture with a MobileNetv3-Large backbone to accurately identify the four histopathological structures associated with acute renal tubular injury in PAS-stained mouse samples. In the segmentation model for four structures, the highest Intersection over Union and the Dice coefficient were obtained for the segmentation of the "glomerulus" class, followed by "necrotic tubules," "healthy tubules," and "tubules with cast" classes. The overall performance of the segmentation algorithm for all classes in the test set included an Intersection over Union of 0.7968 and a Dice coefficient of 0.8772. The Dice scores for the glomerulus, healthy tubules, necrotic tubules, and tubules with cast are 91.78 ± 11.09, 87.37 ± 4.02, 88.08 ± 6.83, and 83.64 ± 20.39%, respectively. The utilization of deep learning in a predictive model has demonstrated promising performance in accurately identifying the degree of injured renal tubules. These results may provide new opportunities for the application of the proposed methods to evaluate renal pathology more effectively.


Asunto(s)
Lesión Renal Aguda , Aprendizaje Profundo , Ratones , Animales , Riñón/patología , Túbulos Renales , Lesión Renal Aguda/patología , Cisplatino , Necrosis/patología
16.
Int Microbiol ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38538991

RESUMEN

The study was conducted to assess the effects of nitrogen (N)-fixing purple nonsulfur bacteria (PNSB) Rhodopseudomonas palustris TLS06, VNW02, VNW64, and VNS89 on soil fertility, N uptake, essential oil (EO) content, growth, and yield of lemon balm. The experiment followed a completely randomized block design with 9 treatments and 3 replications. The treatments consisted of (i) applying 100% N as the recommended fertilizer rate (RFR), (ii) applying 85% N as RFR, (iii) applying 70% N as RFR, (iv) applying 55% N as RFR, (v) the treatment ii combined with N-PNSB, (vi) the treatment iii combined with N-PNSB, (vii) the treatment iv combined with N-PNSB, (viii) 0% as RFR combined with N-PNSB, and (ix) 0% N as RFR. The results showed that applying N-PNSB increased the plant height, and the number of primary branches in both seasons. In addition, the treatment without N fertilizer combined with N-PNSB increased stem leaf biomass by 41.2 and 50.3% in both seasons as compared with the treatment without neither N fertilizer nor N-PNSB. For soil properties, among treatments without N fertilizer, the treatment with N-PNSB increased concentrations of NH4+, soluble P, and exchangeable K+ by 41.3, 41.4, and 26.8%, respectively, as compared with the treatment without N-PNSB at the end of the second season. Applying 85% N as RFR combined with N-PNSB had a greater yield by 5.78-11.8% as compared with the treatment with 100% N as RFR, and a greater EO content by 23% as compared with the treatment with 85% N as RFR.

17.
Sci Rep ; 14(1): 6969, 2024 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521815

RESUMEN

Fluorescence nanosilica-based cell tracker has been explored and applied in cell biological research. However, the aggregation of these nanoparticles at physiological pH is still the main limitation. In this research, we introduced a novel fluorescence nano-based cell tracker suitable for application in live cells. The silica-coated fluorescein isothiocyanate isomer (FITC-SiO2) nanoparticles (NPs) were modified with carboxymethylsilanetriol disodium salt (FITC-SiO2-COOH), integrating the dianion form of FITC molecules. This nanosystem exhibited superior dispersion in aqueous solutions and effectively mitigated dye leakage. These labeled NPs displayed notable biocompatibility and minimal cytotoxicity in both in vitro and in vivo conditions. Significantly, the NPs did not have negative implications on cell migration or angiogenesis. They successfully penetrated primary fibroblasts, human umbilical vein endothelial cells and HeLa cells in both 2D and 3D cultures, with the fluorescence signal enduring for over 72 h. Furthermore, the NP signals were consistently observed in the developing gastrointestinal tract of live medaka fish larvae for extended periods during phases of subdued digestive activity, without manifesting any apparent acute toxicity. These results underscore the promising utility of FITC-SiO2-COOH NPs as advanced live cell trackers in biological research.


Asunto(s)
Nanopartículas , Dióxido de Silicio , Animales , Humanos , Células HeLa , Fluoresceína-5-Isotiocianato , Dióxido de Silicio/química , Células Endoteliales , Nanopartículas/toxicidad , Nanopartículas/química
18.
Small Methods ; : e2400094, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426646

RESUMEN

Recent developments in the synthesis of hybrid organic-inorganic halide perovskite quantum dots (HP-QDs) through compositional adjustments have highlighted their potential applications in the fields of photovoltaics and light sources due to their unique optoelectronic properties. However, traditional methods to fine-tune their composition involve repetitive, labor-intensive, and costly processes. Herein, the utilization of a continuous flow chemistry approach is developed, in combination with a Proportional-Integral (PI) feedback control system as an effective method for producing on-demand methylammonium lead bromoiodide (MAPbBrx I3-x ) HP-QDs. The PI feedback control allows for real-time optimization of the flow rates of halide precursor solutions (halide PSs), enabling the precise tuning of the emission wavelength of HP-QDs. HP-QDs having an emission wavelength of 550 and 650 nm are synthesized through a blue-shifted and red-shifted algorithm, respectively, from any arbitrary reaction condition within 400 s. The iterative process through the PI feedback control produces the target HP-QDs with short rise time and low overshoot. The proposed automatic flow chemistry system integrated with a universal and accessible control algorithm of PI can generate the target HP-QDs with high accuracy, stability, and robustness, demonstrating a significant advancement in constructing an autonomous flow chemistry synthetic system.

19.
Radiol Case Rep ; 19(5): 1917-1925, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38434785

RESUMEN

Necrotizing pneumonia (NP) is characterized by destruction of pulmonary tissue, resulting in multiple thin-walled cavities. There are limited reports on NP and parapneumonic effusion cases in children associated with Pseudomonas aeruginosa. Currently, there is no consensus regarding the optimal timing for video-assisted thoracoscopic surgery (VATS) following failure of chest tube placement and antibiotic treatment. A healthy 20-month-old child was hospitalized with symptoms of community-acquired pneumonia, progressing to severe NP and parapneumonic effusion. Despite receiving broad-spectrum antibiotics and chest tube placement on the third day of treatment, the condition continued to deteriorate, prompting VATS intervention on the sixth day. The presence of a "split pleural sign" and extensive lung necrosis on chest computed tomography contributed to initial treatment failure. Multidrug resistance P. aeruginosa was identified through nasal trachea aspiration specimens on the eighth day of treatment, leading to an adjustment in antibiotic therapy to high-dose meropenem and amikacin. Subsequently, the patient became afebrile, showed clinical improvement, and was discharged after 35 days of treatment. Through this case, we aim to emphasize an unusual pathogenic bacteria in the context of NP and the need for standardized surgical interventions in pediatric patients with NP.

20.
BMC Cancer ; 24(1): 176, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317094

RESUMEN

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.


Asunto(s)
Afatinib , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Vietnam/epidemiología
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