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Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.
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Dual-lumen microcatheters (DLMC) are utilized in challenging wiring scenarios as well as for contrast and medication injections. Nonetheless, lesion characterization remains extremely challenging in many cases. We describe a DLMC-facilitated technique which can assist in locating the distal anastomosis while navigating an occluded bypass graft during retrograde chronic total occlusion recanalization, as well as in the differential diagnosis of abrupt vessel closure. This "DLMC Pullback Injection" technique is performed by injecting contrast through the over-the-wire port of the DLMC, while the latter is quickly pulled back across the region of interest in a dynamic fashion. We believe this technique has the potential to solve challenging scenarios and to enrich the complex percutaneous coronary intervention operator's armamentarium.
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Agriculture is vital for global food security, and irrigation is essential for improving crop yields. However, irrigation can pose challenges such as mineral scarcity and salt accumulation in the soil, which negatively impact plant growth and crop productivity. While numerous studies have focused on enhancing plant tolerance to high salinity, research targeting various ecotypes of Arabidopsis thaliana has been relatively limited. In this study, we aimed to identify salt-tolerant ecotypes among the diverse wild types of Arabidopsis thaliana and elucidate their characteristics at the molecular level. As a result, we found that Catania-1 (Ct-1), one of the ecotypes of Arabidopsis, exhibits greater salt tolerance compared to Col-0. Specifically, Ct-1 exhibited less damage from reactive oxygen species (ROS) than Col-0, despite not accumulating antioxidants like anthocyanins. Additionally, Ct-1 accumulated more potassium ions (K+) in its shoots and roots than Col-0 under high salinity, which is crucial for water balance and preventing dehydration. In contrast, Ct-1 plants were observed to accumulate slightly lower levels of Na+ than Col-0 in both root and shoot tissues, regardless of salt treatment. These findings suggest that Ct-1 plants achieve high salinity resistance not by extruding more Na+ than Col-0, but rather by absorbing more K+ or releasing less K+. Ct-1 exhibited higher nitrate (NO3-) levels than Col-0 under high salinity conditions, which is associated with enhanced retention of K+ ions. Additionally, genes involved in NO3- transport and uptake, such as NRT1.5 and NPF2.3, showed higher transcript levels in Ct-1 compared to Col-0 when exposed to high salinity. However, Ct-1 did not demonstrate significantly greater resistance to osmotic stress compared to Col-0. These findings suggest that enhancing plant tolerance to salt stress could involve targeting the cellular processes responsible for regulating the transport of NO3- and K+. Overall, our study sheds light on the mechanisms of plant salinity tolerance, emphasizing the importance of K+ and NO3- transport in crop improvement and food security in regions facing salinity stress.
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Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 109/L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.
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COVID-19 , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Masculino , Femenino , Niño , COVID-19/epidemiología , COVID-19/diagnóstico , COVID-19/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Vietnam/epidemiología , Preescolar , Adolescente , Lactante , SARS-CoV-2/aislamiento & purificación , Pronóstico , Recuento de Linfocitos , Unidades de Cuidado Intensivo Pediátrico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismoRESUMEN
Ferroptosis, an iron-dependent form of non-apoptotic cell death, plays a pivotal role in various diseases and is gaining considerable attention in the realm of endometriosis. Considering the classical pathomechanism theories, we hypothesized that ferroptosis, potentially driven by increased iron content at ectopic sites, may contribute to the progression of endometriosis. This retrospective case-control study provides a comprehensive immunohistochemical assessment of the expression and tissue distribution of established ferroptosis markers: GPX4, ACSL4, and TfR1 in endometriosis patients. The case group consisted of 38 women with laparoscopically and histologically confirmed endometriosis and the control group consisted of 18 women with other gynecological conditions. Our study revealed a significant downregulation of GPX4 in stromal cells of endometriosis patients (M = 59.7% ± 42.4 versus 90.0% ± 17.5 in the control group, t (54) = -2.90, p = 0.005). This finding aligned with slightly, but not significantly, higher iron levels detected in the blood of endometriosis patients, using hemoglobin as an indirect predictor (Hb 12.8 (12.2-13.5) g/dL versus 12.5 (12.2-13.4) g/dL in the control group; t (54) = -0.897, p = 0.374). Interestingly, there was no concurrent upregulation of TfR1 (M = 0.7 ± 1.2 versus 0.2 ± 0.4 for EM, t (54) = 2.552, p = 0.014), responsible for iron uptake into cells. Our empirical findings provide support for the involvement of ferroptosis in the context of endometriosis. However, variances in expression patterns within stromal and epithelial cellular subsets call for further in-depth investigations.
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Coenzima A Ligasas , Endometriosis , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Receptores de Transferrina , Humanos , Femenino , Endometriosis/metabolismo , Endometriosis/patología , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Adulto , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Estudios de Casos y Controles , Estudios Retrospectivos , Antígenos CD/metabolismo , Antígenos CD/genética , Hierro/metabolismo , Células del Estroma/metabolismo , Células del Estroma/patología , Persona de Mediana Edad , Biomarcadores/metabolismoRESUMEN
Walking patterns are modified during load carriage, resulting in an increased activation of lower limb muscles and energy expenditure. Negative effects of load carriage could be minimized by wearing an exoskeleton, but evidence on the effects are conflicting. The objectives of this study were to describe the influence of an adjustable, passive load-bearing exoskeleton on the metabolic cost of walking (MCW) and associated muscle activations, and to explore changes in MCW after a familiarization process. Thirteen participants walked on a treadmill with a 22.75 kg payload at six preselected speeds (from 0.67 to 1.56 m/s) under three walking conditions: 1) without exoskeleton (NoExo); 2) with exoskeleton before familiarization (ExoPre); and 3) with exoskeleton after familiarization (ExoPost). Metabolic data was normalized to walking speed to provide MCW. Multi-muscle surface electromyography (EMG) was time and amplitude normalized to the gait cycle to provide muscle activation patterns. The familiarization occurred over three weeks including exposure to the exoskeleton. Differences in MCW and muscle activations were compared using a nonparametric analysis of longitudinal data. There were statistically significant increases in MCW for all speeds in the ExoPre and ExoPost conditions compared the NoExo. The average muscle activation showed an increase during ExoPre and ExoPost for the three speeds evaluated. Post-hoc analysis showed no significant effect of the familiarization period on metabolic data. In conclusion, a first exposure to the adjustable exoskeleton increased MCW and muscle activations, but the familiarization process did not provide any benefits toward a reduction in MCW or reduction in muscle activations at all speeds evaluated.
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Electromiografía , Dispositivo Exoesqueleto , Extremidad Inferior , Músculo Esquelético , Consumo de Oxígeno , Caminata , Soporte de Peso , Humanos , Caminata/fisiología , Masculino , Músculo Esquelético/fisiología , Adulto , Extremidad Inferior/fisiología , Consumo de Oxígeno/fisiología , Femenino , Adulto Joven , Soporte de Peso/fisiología , Metabolismo Energético/fisiología , Marcha/fisiología , Fenómenos Biomecánicos , Voluntarios SanosRESUMEN
INTRODUCTION: Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital. METHODS: This case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls. DISCUSSION: This study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement.
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Complicaciones Infecciosas del Embarazo , Sepsis , Humanos , Femenino , Embarazo , Estudios de Casos y Controles , Factores de Riesgo , Sepsis/epidemiología , Sepsis/microbiología , Vietnam/epidemiología , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/farmacologíaRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Statins are recommended for treatment of dyslipidemia to reduce the overall cardiovascular risk in patients with NAFLD. However, statin treatment was underutilized and the effect of statins on liver enzymes remained unclear in this patient population. OBJECTIVES: This study aimed to provide real-world evidence of the safety and effect of statin use in patients with NAFLD. METHODS: We conducted a cross-sectional survey study of adults with NAFLD using pooled data from the US NHANES database 2009-2018. NAFLD was defined by Fatty Liver Index (FLI) ≥ 60 and United States Fatty Liver Index (USFLI) ≥ 30. Multivariate regression analyses adjusted for baseline clinical and demographic characteristics were performed to compare the liver enzymes and lipid profile between statin and non-statin users. RESULTS: The study included 2,533 adults with NAFLD, representing 22.6 million individuals in the US, with 27% receiving statin treatment between 2009 and 2018. The mean differences of liver enzymes for AST, ALT, ALP, and GGT between statin and non-statin users were -0.86 (p=0.539), -3.49 (p=0.042), -0.25 (p=0.913), and 0.57 (p=0.901), respectively. In individuals with NAFLD and dyslipidemia, total cholesterol and LDL levels were significantly lower in statin users compared to non-statin users (mean difference, -28.9; p<0.001 and -27.7; p<0.001). CONCLUSION: The use of statins was not associated with elevated liver enzymes in patients with NAFLD. Significantly lower levels of ALT, total cholesterol, and LDL were observed in statin users compared to non-statin users.
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As the most frequent cause of acquired myopathy, toxic myopathies are characterised by clinicopathological features that vary depending on the mode of action of the drugs or toxins involved. Although a large number of substances can induce myotoxicity, the main culprits are statins, alcohol, and corticosteroids. A rigorous, well-organised diagnostic approach is necessary to obtain a rapid diagnosis. For early diagnosis and management, it is important for clinicians to be aware that most toxic myopathies are potentially reversible, and the goal of treatment should be to avoid serious muscle damage.
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Artemisinin (ART) combination therapy is the main treatment for malaria. Pfk13 mutations (or K13 mutations, Kelch 13) are associated with ART resistance. This study aims to conduct a systematic review and meta-analysis of the prevalence of K13 mutations with ART resistance in malaria-endemic countries. An electronic search of studies in 2018 and a manual search in 2020 were performed to identify relevant studies. The risk of bias was assessed using the National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies. Data analysis was performed using R 4.1.0. Heterogeneity was estimated using the statistic I2 and Cochran Q test. A total of 170 studies were included in our review. Of these, 55 studies investigated the prevalence of K13 mutations in Southeast Asia. The meta-analysis showed that Southeast Asia had the highest prevalence of K13 mutations, whereas Africa, South America, Oceania, and other Asian countries outside Southeast Asia had a low prevalence of K13 mutations. The C580Y mutation was the most common in Southeast Asia with 35.5% (95%CI: 25.4-46.4%), whereas the dominant mutation in Africa was K189T (22.8%, 95%CI: 7.6-43.2%). This study revealed the emergence of ART resistance associated with K13 mutations in Southeast Asia. The diversity of each type of K13 mutation in other regions was also reported.
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Antimaláricos , Artemisininas , Polimorfismo Genético , Artemisininas/uso terapéutico , Humanos , Antimaláricos/uso terapéutico , Prevalencia , Resistencia a Medicamentos/genética , Plasmodium falciparum/genética , Plasmodium falciparum/efectos de los fármacos , Malaria/tratamiento farmacológico , Malaria/epidemiología , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Mutación , Proteínas Protozoarias/genética , Asia Sudoriental/epidemiologíaRESUMEN
BACKGROUND: Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs). OBJECTIVE: We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma. PATIENTS AND METHODS: We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946). RESULTS: The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I2 = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule. CONCLUSIONS: This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment.
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Inhibidores de la Angiogénesis , Neoplasias , Inhibidores de Proteínas Quinasas , Humanos , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacologíaRESUMEN
Background and Aim: Small rectosigmoid colorectal polyps (<10 mm) are prevalent, with a low prevalence of advanced neoplastic lesions. The "diagnose-and-leave" strategy, employing narrow band imaging (NBI), is gaining popularity for its safety and cost-effectiveness by reducing polypectomy complications and minimizing histopathology expenses. This study assessed the diagnostic efficacy of NBI with dual focus (DF) magnification for real-time neoplastic prediction of rectosigmoid polyps and explored the feasibility of implementing this strategy in Vietnam. Methods: In a prospective single-center study, 307 rectosigmoid polyps from 245 patients were analyzed using three consecutive endoscopic modes: white light endoscopy (WLE), NBI, and NBI-DF. Endoscopists assessed polyps for size, location, macroscopic shape, optical diagnosis, and confidence levels before histopathological evaluation. High confidence was assigned when the polyp exhibited all features of a single histology type. Predictions were compared with final histopathology results. Results: Of the total, 237 (77.2%) were diminutive (≤5 mm) polyps, and 18 (5.8%) were advanced neoplastic lesions. WLE + NBI and WLE + NBI + NBI-DF exhibited significantly higher accuracy compared to WLE (88.6% and 90.2% vs 74.2%, P < 0.01). For diminutive polyps, the DF mode significantly increased the rate of high-confidence optical diagnoses (89.1% vs 94.9%, P < 0.001). WLE + NBI + NBI-DF demonstrated high sensitivity (90.1%), specificity (95.5%), and negative predictive value (93.4%) in high-confidence predictions, enabling the implementation of the "diagnose-and-leave" strategy. This approach would have reduced 58.2% of unnecessary polypectomies without missing any advanced neoplastic lesions. Conclusion: NBI and DF modes provide accurate neoplastic predictions for rectosigmoid polyps. For diminutive polyps, DF magnification improves the confidence level of the optical diagnosis, allowing the safe implementation of the "diagnose-and-leave" strategy.
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Cultivated meat (CM) offers a sustainable and ethical alternative to conventional animal agriculture, involving cell maturation in a controlled environment. To emulate the structural complexity of traditional meat, the development of animal-free and edible scaffolds is crucial, providing vital physical and biological support during tissue development. The aligned vascular bundles of the decellularised asparagus scaffold were selected to facilitate the attachment and alignment of murine myoblasts (C2C12) and porcine adipose-derived mesenchymal stem cells (pADMSCs). Muscle differentiation was assessed through immunofluorescence staining with muscle markers, including Myosin heavy chain (MHC), Myogenin (MYOG), and Desmin. The metabolic activity of Creatine Kinase in C2C12 differentiated cells significantly increased compared to proliferated cells. Quantitative PCR analysis revealed a significant increase in Myosin Heavy Polypeptide 1 (MYH1) and MYOG expression compared to Day 0. These results highlight the application of decellularised plant scaffold (DPS) as a promising, edible material conducive to cell attachment, proliferation, and differentiation into muscle tissue. To create a CM prototype with biological mimicry, pADMSC-derived muscle and fat cells were also co-cultured on the same scaffold. The co-culture was confirmed through immunofluorescence staining of muscle markers and LipidTOX staining, revealing distinct muscle fibres and adipocytes containing lipid droplets respectively. Texture profile analysis conducted on uncooked CM prototypes and pork loin showed no significant differences in textural values. However, the pan-fried CM prototype differed significantly in hardness and chewiness compared to pork loin. Understanding the scaffolds' textural profile enhances our insight into the potential sensory attributes of CM products. DPS shows potential for advancing CM biomanufacturing.
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Enzymatic hydrolysis of edible bird's nest (EBN) has attracted great interest in both scientific and commercial fields due to the enhancement of solubility and nutraceutical values. The present study attempted to investigate the hydrolysis of EBN with papaya (Carica papaya L.), pineapple (Ananas comosus (L.) Merr.), and cantaloupe (Cucumis melo L.) juices as well as two commercial enzymes papain and bromelain. Our analysis revealed that EBN hydrolysis with pineapple juice and bromelain produced a degree of hydrolysis (DH) value of approximately 27 % while it was about 25 % for the hydrolysis with cantaloupe juice and 22 % for the hydrolysis with papaya juice and papain after 4 h of treatment. When EBN was digested by fruit juices and enzymes, the protein solubility and free sialic acid content were increased and the highest values were achieved for EBN hydrolysis with pineapple juice and bromelain (estimately 11 mg/mL of soluble protein and 18 g/kg of free sialic acid). The ABTSâ¢+-scavenging, â¢OH-scavenging, and anti-tyrosinase capacities were higher in the EBN hydrolysates by papaya juice (IC50 of 0.034, 0.108, and 0.419 mg/mL, respectively), pineapple juice (IC50 of 0.025, 0.045, and 0.190 mg/mL, respectively), and cantaloupe juice (IC50 of 0.031 mg/mL, 0.056, and 0.339 mg/mL, respectively) than in the hydrolysates by unhydrolyzed EBN (IC50 of 0.094, 0.366, and 1.611 mg/mL, respectively). An improvement in ABTSâ¢+-scavenging, â¢OH-scavenging, and anti-tyrosinase abilities was also observed for the hydrolysates by papain (IC50 of 0.041, 0.129, and 0.417 mg/mL, respectively) and bromelain (IC50 of 0.025, 0.069, and 0.336 mg/mL, respectively) but in a lesser extent as compared to the hydrolysates by respective papaya and pineapple juices. Noticeably, the EBN hydrolysates by fruit juices remarkably enhanced the wound closure in human fibroblasts by about 1.4-1.8 times after 24 h of treatment whereas this property was insignificant in the hydrolysates by enzymes. As papaya, pineapple, and cantaloupe juices are easily obtainable and have pleasant flavors, our results provide a possible method to hydrolyze EBN and apply the resultant hydrolysates in functional food products.
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Metal node engineering, which can optimize the electronic structure and modulate the composition of poor electrically conductive metal-organic frameworks, is of great interest for electrochemical natural seawater splitting. However, the mechanism underlying the influence of mixed-metal nodes on electrocatalytic activities is still ambiguous. Herein, a strategic design is comprehensively demonstrated in which mixed Ni and Co metal redox-active centers are uniformly distributed within NH2-Fe-MIL-101 to obtain a synergistic effect for the overall enhancement of electrocatalytic activities. Three-dimensional mixed metallic MOF nanosheet arrays, consisting of three different metal nodes, were in situ grown on Ni foam as a highly active and stable bifunctional catalyst for urea-assisted natural seawater splitting. A well-defined NH2-NiCoFe-MIL-101 reaches 1.5 A cm-2 at 360 mV for the oxygen evolution reaction (OER) and 0.6 A cm-2 at 295 mV for the hydrogen evolution reaction (HER) in freshwater, substantially higher than its bimetallic and monometallic counterparts. Moreover, the bifunctional NH2-NiCoFe-MIL-101 electrode exhibits eminent catalytic activity and stability in natural seawater-based electrolytes. Impressively, the two-electrode urea-assisted alkaline natural seawater electrolysis cell based on NH2-NiCoFe-MIL-101 needs only 1.56 mV to yield 100 mA cm-2, much lower than 1.78 V for alkaline natural seawater electrolysis cells and exhibits superior long-term stability at a current density of 80 mA cm-2 for 80 h.
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Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial carcinoma, assessed by either an AI Measurement Model (AIM-PD-L1) or expert pathologists. The concordance among pathologists and between pathologists and AIM-PD-L1 was determined. The positivity rate of ≥ 1%TC PD-L1 was between 20-30% for 8/10 pathologists, and the degree of agreement and scoring distribution for among pathologists and between pathologists and AIM-PD-L1 was similar both scored as a continuous variable or using the pre-defined cutoff. Numerically higher score variation was observed with the 22C3 assay than with the 28-8 assay. A 2-h training module on the 28-8 assay did not significantly impact manual assessment. Cases exhibiting significantly higher variability in the assessment of PD-L1 expression (mean absolute deviation > 10) were found to have patterns of PD-L1 staining that were more challenging to interpret. An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1.
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Inteligencia Artificial , Antígeno B7-H1 , Biomarcadores de Tumor , Variaciones Dependientes del Observador , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Reproducibilidad de los Resultados , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias Urológicas/patología , Neoplasias Urológicas/metabolismo , Inmunohistoquímica/métodos , Patólogos , Urotelio/patología , Urotelio/metabolismoRESUMEN
Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.
[Box: see text].
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Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN , Feto , Humanos , Femenino , Embarazo , Variaciones en el Número de Copia de ADN/genética , Vietnam , Adulto , Estudios Retrospectivos , Diagnóstico Prenatal/métodos , Aneuploidia , Pueblo Asiatico/genética , Ultrasonografía Prenatal/métodos , Pueblos del Sudeste AsiáticoRESUMEN
BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.
Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Países en Desarrollo , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Marcadores Genéticos , Metilación de ADN , Carcinoma de Células Escamosas/genética , Papillomaviridae/genética , Frotis Vaginal/métodos , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).
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Anafilaxia , Hipersensibilidad a las Drogas , Humanos , Anafilaxia/epidemiología , Francia/epidemiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Hipersensibilidad a las Drogas/epidemiología , Bloqueantes Neuromusculares/efectos adversos , Periodo Perioperatorio , Adolescente , Adulto Joven , Antibacterianos/efectos adversos , Anciano de 80 o más Años , Pruebas Cutáneas , NiñoRESUMEN
BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.