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1.
Asian J Surg ; 2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-39054123

RÉSUMÉ

BACKGROUND: Preoperative prediction of visual outcomes following pituitary adenoma surgery is challenging yet crucial for clinical decision-making. We aimed to develop models using radiomics from multiparametric MRI to predict postoperative visual outcomes. METHODS: A cohort of 152 patients with pituitary adenoma was retrospectively enrolled and divided into recovery and non-recovery groups based on visual examinations performed six months after surgery. Radiomic features of the optic chiasm were extracted from preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1-weighted imaging (T1CE). Predictive models were constructed using the least absolute shrinkage and selection operator wrapped with a support vector machine through five-fold cross-validation in the development cohort and evaluated in an independent test cohort. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Four models were established based on radiomic features selected from individual or combined sequences. The AUC values of the models based on T1WI, T2WI and T1CE were 0.784, 0.724, 0.822 in the development cohort, and 0.767, 0.763, 0.794 in the independent test cohort. The multiparametric model demonstrated superior performance among the four models, with AUC of 0.851, accuracy of 0.832. sensitivity of 0.700, specificity of 0.910 in the development cohort, and AUC of 0.847, accuracy of 0.800, sensitivity of 0.882 and specificity of 0.750 in the independent test cohort. CONCLUSION: The multiparametric model utilizing radiomics of optic chiasm outperformed single-sequence models in predicting postoperative visual recovery in patients with pituitary adenoma, serving as a novel approach for enhancing personalized treatment strategies.

2.
Ann Vasc Surg ; 2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39067852

RÉSUMÉ

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a complex disease with environmental and genetic risk factors. Polygenic risk scores (PRS) based on disease-specific risk-associated single nucleotide variants (SNVs) have demonstrated effectiveness in stratifying individual-level disease risk for cardiovascular diseases. This prospective cohort study assessed associations of PRS of AAA (PRSAAA) with risk of incident AAA, analyzed the effectiveness of a combined clinical-genetic risk model, and explored the clinical utility of the model in identifying high-risk individuals for AAA screening. METHODS: PRSAAA was calculated using 911,440 SNVs and PRSCAD was calculated using 2,324,683 SNVs derived from mixed ancestry genome wide association studies. The UK Biobank was used as the study cohort. All individuals with complete genetic data available and no diagnosis of AAA at time of recruitment were included in the analysis and followed prospectively to assess for incident AAA. A PRS informed clinical model, Prob-AAA, was developed using clinically significant variables and PRSAAA. RESULTS: 481,105 individuals were included in the analysis with 2,668 incident AAA cases. Incident AAA increased from 0.30% to 0.93% between the lowest and highest decile of PRSAAA; similarly, severe AAA, requiring surgery and/or presenting with rupture, increased from 23% to 39% of incident AAA cases across deciles. PRSAAA was a predictor of incident AAA diagnosis (HR 2.06 [1.70 - 2.48]) independent of other clinical risk factors including male sex, older age, and smoking history. Prob-AAA was an independent predictor of incident AAA (HR 1.92 [1.69 - 2.20]), and identified 9.6% of cases of incident AAA compared to only 4.2% by PRSAAA. Current screening guidelines captured 5.7% of the overall cohort, with an incident AAA rate of approximately 3.2%. Amongst males not included by current guidelines, Prob-AAA identified an additional cohort, approximately 2% of the overall cohort, with a similar rate of incident AAA. CONCLUSIONS: Prob-AAA, a PRS informed clinical model for AAA, improved upon the predictive power of current, clinical risk factor informed, screening guidelines for AAA.

3.
Plant Cell Rep ; 43(8): 202, 2024 Jul 29.
Article de Anglais | MEDLINE | ID: mdl-39073636

RÉSUMÉ

KEY MESSAGE: E1 holoenzyme was extensively Hyp-O-glycosylated at the proline rich linker region in plants, which substantially increased the molecular size and improved the enzymatic digestibility of the biomass of transgenic plants. Thermophilic E1 endo-1,4-ß-glucanase derived from Acidothermus cellulolyticus has been frequently expressed in planta to reconstruct the plant cell wall to overcome biomass recalcitrance. However, the expressed holoenzyme exhibited a larger molecular size (~ 100 kDa) than the theoretical one (57 kDa), possibly due to posttranslational modifications in the recombinant enzyme within plant cells. This study investigates the glycosylation of the E1 holoenzyme expressed in tobacco plants and determines its impact on enzyme activity and biomass digestibility. The E1 holoenzyme, E1 catalytic domain (E1cd) and E1 linker (E1Lk) were each expressed in tobacco plants and suspension cells. The accumulation of holoenzyme was 2.0- to 2.3- times higher than that of E1cd. The proline-rich E1Lk region was extensively hydroxyproline-O-glycosylated with arabinogalactan polysaccharides. Compared with E1cd, the holoenzyme displayed a broader optimal temperature range (70 to 85 ºC). When grown in greenhouse, the expression of E1 holoenzyme induced notable phenotypic changes in plants, including delayed flowering and leaf variegation post-flowering. However, the final yield of plant biomass was not significantly affected. Finally, plant biomass engineering with E1 holoenzyme showed 1.7- to 1.8-fold higher saccharification efficiency than the E1cd lines and 2.4- to 2.7-fold higher than the wild-type lines, which was ascribed to the synergetic action of the E1Lk and cellulose binding module in reducing cell wall recalcitrance.


Sujet(s)
Biomasse , Cellulase , Hydroxyproline , Nicotiana , Végétaux génétiquement modifiés , Glycosylation , Cellulase/métabolisme , Cellulase/génétique , Nicotiana/génétique , Nicotiana/métabolisme , Hydroxyproline/métabolisme , Paroi cellulaire/métabolisme , Cellulose/métabolisme , Protéines recombinantes/métabolisme , Protéines recombinantes/génétique , Caldicellulosiruptor/génétique , Caldicellulosiruptor/métabolisme
4.
Article de Anglais | MEDLINE | ID: mdl-38862429

RÉSUMÉ

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.


Sujet(s)
COVID-19 , SARS-CoV-2 , Humains , SARS-CoV-2/génétique , COVID-19/virologie , COVID-19/diagnostic , Séquençage nucléotidique à haut débit/méthodes , Analyse de séquence d'ADN/méthodes , Escherichia coli/génétique , Mutation
5.
Chem Commun (Camb) ; 60(55): 7081-7084, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38896044

RÉSUMÉ

In this report, we show that a very common modification (especially in tRNA), dihydrouridine, was efficiently produced by photoreduction of the canonical pyrimidine ribonucleoside, uridine in formamide. Formamide not only acts as a solvent in this reaction, but also as the reductant. The other three components of the canonical alphabet (C, A, G) remained intact under the same conditions, suggesting that dihydrouridine might have coexisted with all four canonical RNA nucleosides (C, U, A, G) at the dawn of life.


Sujet(s)
Formamides , Oxydoréduction , Uridine , Uridine/composition chimique , Uridine/analogues et dérivés , Uridine/synthèse chimique , Formamides/composition chimique , Processus photochimiques
6.
J Stroke Cerebrovasc Dis ; 33(8): 107788, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38878393

RÉSUMÉ

BACKGROUND: Electroacupuncture (EA) could represent a clinically effective treatment strategy for patients with vascular cognitive impairment no dementia (VCIND). This randomized trial aims to explore the underlying mechanism of EA in VCIND patients through cognitive function assessment and neuroimaging assessment. METHODS: 140 eligible patients with VCIND were recruited and randomly divided into EA group (n = 70) and Control group (n = 70). The Montreal Cognitive Assessment (MoCA), and the Auditory Verbal Learning Test (AVLT), the Stroop color-naming task (STROOP), and the resting-state functional magnetic resonance imaging assessment. The EA group received treatment for 30 min/day, 5 times/week, for 8 weeks. RESULTS: EA intervention could increase the MoCA score and improve the neutral and consistency response of the STROOP test in VCIND patients (P < 0.05). fMRI functional connectivity analysis showed that, after EA, the default mode network (DMN) function of the posterior cingulate gyrus, left middle frontal gyrus, left anterior cingulate gyrus, left and right superior temporal gyrus, right insula, left precentral gyrus and other brain regions were significantly higher than that in the control group. The functional connectivity between the posterior cingulate gyrus-left middle frontal gyrus and the posterior cingulate gyrus-right superior temporal gyrus was positively correlated with cognitive function (P < 0.05). Gray Matter Volume increased in VCIND after EA(P < 0.05). CONCLUSIONS: EA can increase the functional connectivity between posterior cingulate gyrus-other gyri in VCIND patients. The functional connectivity is positively correlated with cognitive function.


Sujet(s)
Cognition , Dysfonctionnement cognitif , Électroacupuncture , Imagerie par résonance magnétique , Humains , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Résultat thérapeutique , Dysfonctionnement cognitif/thérapie , Dysfonctionnement cognitif/physiopathologie , Dysfonctionnement cognitif/étiologie , Dysfonctionnement cognitif/diagnostic , Facteurs temps , Tests de l'état mental et de la démence , Réseau du mode par défaut/physiopathologie , Réseau du mode par défaut/imagerie diagnostique , Test de Stroop , Encéphale/physiopathologie , Encéphale/imagerie diagnostique
7.
Diabetes ; 73(8): 1352-1360, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38758294

RÉSUMÉ

Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (ß-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms. Associations were tested with general linear models and Cox regression with adjustment for age, sex, and principal components. Sensitivity analyses included adjustment for BMI. Higher ß-cell pPS was associated with lower insulinogenic index and corrected insulin response at 1-year follow-up with adjustment for baseline measures (effect per pPS SD -0.04, P = 9.6 × 10-7, and -8.45 µU/mg, P = 5.6 × 10-6, respectively) and with increased diabetes incidence with adjustment for BMI at nominal significance (hazard ratio 1.10 per SD, P = 0.035). The liver/lipid pPS was associated with reduced 1-year baseline-adjusted triglyceride levels (effect per SD -4.37, P = 0.001). There was no significant interaction between T2D pPS and randomized groups. The remaining pPS were associated with baseline measures only. We conclude that despite interventions for diabetes prevention, participants with a high genetic burden of the ß-cell cluster pPS had worsening in measures of ß-cell function.


Sujet(s)
Diabète de type 2 , Cellules à insuline , État prédiabétique , Humains , Cellules à insuline/métabolisme , État prédiabétique/génétique , Mâle , Diabète de type 2/génétique , Diabète de type 2/métabolisme , Femelle , Adulte d'âge moyen , Prédisposition génétique à une maladie , Hérédité multifactorielle , Adulte , Incidence
8.
Exp Neurol ; 377: 114782, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38641126

RÉSUMÉ

Elevated transport of Caveolin-1 (CAV-1) vesicles within vascular endothelial cells constitutes a significant secondary pathogenic event contributing to the compromise of the blood-brain barrier (BBB) post-traumatic brain injury (TBI). While Wnt/ß-catenin signaling is recognized for its critical involvement in angiogenesis and the maintenance of BBB integrity, its influence on vascular endothelial transcytosis in the aftermath of TBI is not well-defined. This study aims to elucidate the impact of Wnt/ß-catenin signaling on cerebrovascular vesicular transcytosis following TBI. In this experiment, adult male wild-type (WT) C57BL/6 mice underwent various interventions. TBI was induced utilizing the controlled cortical impact technique. Post-TBI, mice were administered either an inhibitor or an agonist of Wnt signaling via intraperitoneal injection. Recombinant adeno-associated virus (rAAV) was administered intracerebroventricularly to modulate the expression of the CAV-1 inhibitory protein, Major facilitator superfamily domain-containing 2a (Mfsd2a). This research utilized Evans blue assay, Western blot analysis, immunofluorescence, transmission electron microscopy, and neurobehavioral assessments. Post-TBI observations revealed substantial increases in macromolecule (Evans blue and albumin) leakage, CAV-1 transport vesicle count, astrocyte end-feet edema, and augmented aquaporin-4 (AQP4) expression, culminating in BBB disruption. The findings indicate that Wnt signaling pathway inhibition escalates CAV-1 transport vesicle activity and aggravates BBB compromise. Conversely, activating this pathway could alleviate BBB damage by curtailing CAV-1 vesicle presence. Post-TBI, there is a diminution in Mfsd2a expression, which is directly influenced by the modulation of WNT signals. Employing a viral approach to regulate Mfsd2a, we established that its down-regulation undermines the protective benefits derived from reducing CAV-1 transport vesicles through WNT signal enhancement. Moreover, we verified that the WNT signaling agonist LiCl notably ameliorates neurological deficits following TBI in mice. Collectively, our data imply that Wnt/ß-catenin signaling presents a potential therapeutic target for safeguarding against BBB damage and enhancing neurological function after TBI.


Sujet(s)
Barrière hémato-encéphalique , Lésions traumatiques de l'encéphale , Cavéoline-1 , Souris de lignée C57BL , Transcytose , Voie de signalisation Wnt , Animaux , Barrière hémato-encéphalique/métabolisme , Barrière hémato-encéphalique/anatomopathologie , Barrière hémato-encéphalique/effets des médicaments et des substances chimiques , Lésions traumatiques de l'encéphale/métabolisme , Lésions traumatiques de l'encéphale/anatomopathologie , Souris , Mâle , Voie de signalisation Wnt/effets des médicaments et des substances chimiques , Voie de signalisation Wnt/physiologie , Transcytose/effets des médicaments et des substances chimiques , Transcytose/physiologie , Cavéoline-1/métabolisme , Symporteurs
9.
Cancer Lett ; 592: 216903, 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38670307

RÉSUMÉ

High levels of acetyl-CoA are considered a key metabolic feature of metastatic cancers. However, the impacts of acetyl-CoA metabolic accumulation on cancer microenvironment remodeling are poorly understood. In this study, using human hepatocellular carcinoma (HCC) tissues and orthotopic xenograft models, we found a close association between high acetyl-CoA levels in HCCs, increased infiltration of tumor-associated neutrophils (TANs) in the cancer microenvironment and HCC metastasis. Cytokine microarray and enzyme-linked immunosorbent assays (ELISA) revealed the crucial role of the chemokine (C-X-C motif) ligand 1(CXCL1). Mechanistically, acetyl-CoA accumulation induces H3 acetylation-dependent upregulation of CXCL1 gene expression. CXCL1 recruits TANs, leads to neutrophil extracellular traps (NETs) formation and promotes HCC metastasis. Collectively, our work linked the accumulation of acetyl-CoA in HCC cells and TANs infiltration, and revealed that the CXCL1-CXC receptor 2 (CXCR2)-TANs-NETs axis is a potential target for HCCs with high acetyl-CoA levels.


Sujet(s)
Acétyl coenzyme A , Carcinome hépatocellulaire , Chimiokine CXCL1 , Tumeurs du foie , Granulocytes neutrophiles , Microenvironnement tumoral , Animaux , Femelle , Humains , Mâle , Souris , Acétyl coenzyme A/métabolisme , Acétylation , Carcinome hépatocellulaire/anatomopathologie , Carcinome hépatocellulaire/métabolisme , Carcinome hépatocellulaire/génétique , Lignée cellulaire tumorale , Chimiokine CXCL1/métabolisme , Chimiokine CXCL1/génétique , Pièges extracellulaires/métabolisme , Régulation de l'expression des gènes tumoraux , Tumeurs du foie/anatomopathologie , Tumeurs du foie/métabolisme , Tumeurs du foie/génétique , Souris nude , Infiltration par les neutrophiles , Granulocytes neutrophiles/métabolisme , Granulocytes neutrophiles/anatomopathologie , Récepteurs à l'interleukine-8B/métabolisme , Récepteurs à l'interleukine-8B/génétique , Adulte , Adulte d'âge moyen , Sujet âgé , Souris de lignée BALB C
10.
Micromachines (Basel) ; 15(4)2024 Mar 29.
Article de Anglais | MEDLINE | ID: mdl-38675271

RÉSUMÉ

In this paper, we proposed an efficient and high-precision process for fabricating large-area microlens arrays using thermal reflow combined with ICP etching. When the temperature rises above the glass transition temperature, the polymer cylinder will reflow into a smooth hemisphere due to the surface tension effect. The dimensional differences generated after reflow can be corrected using etching selectivity in the following ICP etching process, which transfers the microstructure on the photoresist to the substrate. The volume variation before and after reflow, as well as the effect of etching selectivity using process parameters, such as RF power and gas flow, were explored. Due to the surface tension effect and the simultaneous molding of all microlens units, machining a 3.84 × 3.84 mm2 silicon microlens array required only 3 min of reflow and 15 min of ICP etching with an extremely low average surface roughness Sa of 1.2 nm.

11.
Int J Cardiol ; 404: 131990, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38521508

RÉSUMÉ

BACKGROUND: Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGSIS) and IS-associated diseases such as atrial fibrillation (AF), venous thromboembolism (VTE), coronary artery disease (CAD), hypertension (HTN), and Type 2 diabetes (T2D) may improve the performance of IS risk assessment. METHODS: Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS diagnosis prior to the recruitment. Lifestyle variables (obesity, smoking and alcohol) at the time of study recruitment, clinical diagnoses of IS-associated diseases, PGSIS, and five PGSs for IS-associated diseases were tested using the Cox proportional-hazards model. Predictive performance was assessed using the C-statistic and net reclassification index (NRI). RESULTS: During a median average 12.5-year follow-up, 8374 subjects were diagnosed with IS. Known clinical variables (age, gender, clinical diagnoses of IS-associated diseases, obesity, and smoking) and PGSIS were all independently associated with IS (P < 0.001). In addition, PGSIS and each PGS for IS-associated diseases was also independently associated with IS (P < 0.001). Compared to the clinical model, a joint clinical/PGS model improved the C-statistic for predicting IS from 0.71 to 0.73 (P < 0.001) and significantly reclassified IS risk (NRI = 0.017, P < 0.001), and 6.48% of subjects were upgraded from low to high risk. CONCLUSIONS: Adding PGSs of IS and IS-associated diseases to known clinical risk factors statistically improved risk assessment for IS, demonstrating the supplementary value of inherited susceptibility measurement . However, its clinical utility is likely limited due to modest improvements in predictive values.


Sujet(s)
Fibrillation auriculaire , Diabète de type 2 , Accident vasculaire cérébral ischémique , Accident vasculaire cérébral , Humains , Accident vasculaire cérébral/diagnostic , Accident vasculaire cérébral/épidémiologie , Accident vasculaire cérébral/génétique , Diabète de type 2/complications , Facteurs de risque , Appréciation des risques , Fibrillation auriculaire/diagnostic , Fibrillation auriculaire/épidémiologie , Fibrillation auriculaire/génétique , Obésité/diagnostic , Obésité/épidémiologie , Obésité/génétique
12.
BMJ Open ; 14(3): e084520, 2024 Mar 08.
Article de Anglais | MEDLINE | ID: mdl-38458808

RÉSUMÉ

INTRODUCTION: Lung cancer remains the largest cause of cancer-related deaths worldwide. Surgical removal of non-small cell lung cancer (NSCLC) has the potential to achieve a cure, although there is ongoing debate regarding the significance of removing mediastinal nodes and the optimal extent of lymph node excision. The purpose of this research is to assess the survival outcomes in patients diagnosed with stage I-IIIA NSCLC who received either complete mediastinal lymphadenectomy (CML) or selective mediastinal lymphadenectomy (SML). METHODS AND ANALYSIS: The protocol follows the guidelines recommended in Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, and this meta-analysis will be conducted in accordance with the standard methodology recommended by the Cochrane Collaboration and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidance. We will conduct a comprehensive search for randomised controlled trials and non-randomised studies examining the effectiveness of CML compared with SML in patients with stage I-IIIA NSCLC. Two authors will perform a comprehensive search of the MEDLINE/PubMed, Embase, the Cochrane Library, CNKI, WanFang, Sinomed, VIP and Web of Science databases. There will be no restrictions on language or publication date, and the search will be conducted on 10 April 2024, with ongoing searches for new research. Reference lists will also be checked and pertinent journals will be hand searched. The primary outcomes include overall survival (OS) and disease-free survival (DFS), while the secondary outcomes consist of 1-year, 3-year and 5-year OS rates and 1-year, 3-year and 5-year DFS rates. Two independent reviewers will screen, extract data, assess quality and evaluate the potential for bias in the selected research, with a third acting as arbitrator. Subgroup analyses and sensitivity analyses are planned. The quality of the evidence will be evaluated using Grading of Recommendations Assessment, Development and Evaluation. Review Manager V.5.4 will be used for the analysis and synthesis process. ETHICS AND DISSEMINATION: Ethical review and approval are not necessary for this study because it is based on a secondary analysis of the literature. The results will be submitted for reporting in a peer-reviewed publication. STUDY REGISTRATION: Open Science Framework (https://doi.org/10.17605/OSF.IO/PN7UQ).


Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/chirurgie , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/anatomopathologie , Revues systématiques comme sujet , Méta-analyse comme sujet , Lymphadénectomie/effets indésirables , Plan de recherche
13.
Article de Anglais | MEDLINE | ID: mdl-38461448

RÉSUMÉ

This study investigates the efficiency and influence of microneedle parameters, specifically Needle Point Angle (a) and Needle Height (h), on the diffusion of Cannabidiol (CBD) across varying skin depths. Utilizing the Latin Hypercube Sampling method, twelve distinct cases were analyzed. Observations reveal a consistent high concentration of CBD delivered via the microneedle patch, with a notable decrease in concentration as the depth increases, displaying a non-linear trend. Multivariate polynomial regression offers a quantitative relationship between the variables, with the third-order bivariate fitting providing the most accurate representation. Compared to other CBD delivery mechanisms, microneedle patches present enhanced CBD concentrations, circumventing challenges faced by other methods such as dosage inaccuracy, systemic absorption issues, and CBD degradation. The results highlight the potential of microneedle patches as a promising avenue for optimized transdermal drug delivery.

14.
ACS Biomater Sci Eng ; 10(3): 1435-1447, 2024 03 11.
Article de Anglais | MEDLINE | ID: mdl-38330203

RÉSUMÉ

Addressing the repair of large-scale bone defects has become a hot research topic within the field of orthopedics. This study assessed the feasibility and effectiveness of using porous tantalum scaffolds to treat such defects. These scaffolds, manufactured using the selective laser melting (SLM) technology, possessed biomechanical properties compatible with natural bone tissue. To enhance the osteogenesis bioactivity of these porous Ta scaffolds, we applied calcium phosphate (CaP) and magnesium-doped calcium phosphate (Mg-CaP) coatings to the surface of SLM Ta scaffolds through a hydrothermal method. These degradable coatings released calcium and magnesium ions, demonstrating osteogenic bioactivity. Experimental results indicated that the Mg-CaP group exhibited biocompatibility comparable to that of the Ta group in vivo and in vitro. In terms of osteogenesis, both the CaP group and the Mg-CaP group showed improved outcomes compared to the control group, with the Mg-CaP group demonstrating superior performance. Therefore, both CaP and magnesium-CaP coatings can significantly enhance the osseointegration of three-dimensional-printed porous Ta, thereby increasing the surface bioactivity. Overall, the present study introduces an innovative approach for the biofunctionalization of SLM porous Ta, aiming to enhance its suitability as a bone implant material.


Sujet(s)
Magnésium , Tantale , Porosité , Magnésium/pharmacologie , Titane , Phosphates de calcium/pharmacologie , Lasers
15.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(1): 44-50, 2024 Jan 30.
Article de Chinois | MEDLINE | ID: mdl-38384216

RÉSUMÉ

This study summarizes the application of automatic recognition technologies for patient-ventilator asynchrony (PVA) during mechanical ventilation. In the early stages, the method of setting rules and thresholds relied on manual interpretation of ventilator parameters and waveforms. While these methods were intuitive and easy to operate, they were relatively sensitive in threshold setting and rule selection and could not adapt well to minor changes in patient status. Subsequently, machine learning and deep learning technologies began to emerge and develop. These technologies automatically extract and learn data characteristics through algorithms, making PVA detection more robust and universal. Among them, logistic regression, support vector machines, random forest, hidden Markov models, convolutional autoencoders, long short-term memory networks, one-dimensional convolutional neural networks, etc., have all been successfully used for PVA recognition. Despite the significant advancements in feature extraction through deep learning methods, their demand for labelled data is high, potentially consuming significant medical resources. Therefore, the combination of reinforcement learning and self-supervised learning may be a viable solution. In addition, most algorithm validations are based on a single dataset, so the need for cross-dataset validation in the future will be an important and challenging direction for development.


Sujet(s)
, Ventilation artificielle , Humains , Respirateurs artificiels , Algorithmes ,
16.
J Endocrinol Invest ; 2024 Feb 22.
Article de Anglais | MEDLINE | ID: mdl-38383878

RÉSUMÉ

PURPOSE: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency. METHODS: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels. RESULTS: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01). CONCLUSIONS: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms.

17.
Genome Med ; 16(1): 9, 2024 01 16.
Article de Anglais | MEDLINE | ID: mdl-38225592

RÉSUMÉ

BACKGROUND: Detecting human cancers through cell-free DNA (cfDNA) in blood is a sensitive and non-invasive option. However, capturing multiple forms of epigenetic information remains a technical and financial challenge. METHODS: To address this, we developed multimodal epigenetic sequencing analysis (MESA), a flexible and sensitive approach to capturing and integrating a diverse range of epigenetic features in cfDNA using a single experimental assay, i.e., non-disruptive bisulfite-free methylation sequencing, such as Enzymatic Methyl-seq. MESA enables simultaneous inference of four epigenetic modalities: cfDNA methylation, nucleosome occupancy, nucleosome fuzziness, and windowed protection score for regions surrounding gene promoters and polyadenylation sites. RESULTS: When applied to 690 cfDNA samples from 3 colorectal cancer clinical cohorts, MESA's novel modalities, which include nucleosome fuzziness, and genomic features, including polyadenylation sites, improve cancer detection beyond the traditional epigenetic markers of promoter DNA methylation. CONCLUSIONS: Together, MESA stands as a major advancement in the field by utilizing comprehensive and complementary epigenetic profiles of cfDNA for effective non-invasive cancer detection.


Sujet(s)
Acides nucléiques acellulaires , Tumeurs colorectales , Humains , Acides nucléiques acellulaires/génétique , Nucléosomes/génétique , Méthylation de l'ADN , Épigenèse génétique , Tumeurs colorectales/diagnostic , Tumeurs colorectales/génétique , Marqueurs biologiques tumoraux/génétique
18.
Opt Express ; 32(1): 482-498, 2024 Jan 01.
Article de Anglais | MEDLINE | ID: mdl-38175077

RÉSUMÉ

Polycrystalline zinc selenide is widely used in advanced optical systems due to its superior optical properties. However, the soft and brittle properties bring a challenge for high-quality surface processing. In recent years, elliptical vibration cutting has been proven as a promising method for machining brittle materials. In the present research, a series of grooving and planning experiments were carried out to investigate the machinability of zinc selenide with elliptical vibration cutting. The removal mechanism was analyzed from fracture characteristics, chip morphology, and phase transformation. The results show that elliptical vibration cutting is effective in suppressing cleavage-induced craters. Reducing the nominal cutting speed is beneficial to inhibit the spring back-induced tearing of grains. A 94-time increase in the critical depth of cut was achieved by vibration trajectory optimization compared to ordinary cutting. Moreover, the influence mechanism of feed on the evolution of surface morphology was revealed. Finally, a zinc selenide microlens array was successfully fabricated. The performance was evaluated by geometric parameter measurements and a multiple imaging test. The findings provide a prospective method for ductile regime machining of zinc selenide.

19.
Theranostics ; 14(1): 392-405, 2024.
Article de Anglais | MEDLINE | ID: mdl-38164149

RÉSUMÉ

Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. Methods: We investigated the imaging efficiency and therapy monitoring capacity of [89Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [89Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. Results: In PD-L1-positive patients, [89Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [89Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [18F]FDG (370-555 MBq). [89Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [89Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. Conclusion: [89Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.


Sujet(s)
Anticorps monoclonaux humanisés , Antigène CD274 , Humains , Tomographie par émission de positons/méthodes , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Lignée cellulaire tumorale , Zirconium
20.
Headache ; 64(1): 68-92, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-38071464

RÉSUMÉ

OBJECTIVE: To evaluate response to anti-calcitonin gene-related peptide (CGRP) migraine preventives in a real-world community cohort of persons living with migraine and to identify clinical and genetic characteristics associated with efficacious response. BACKGROUND: Erenumab-aooeb, fremanezumab-vrfm, and galcanezumab-gnlm target CGRP or its receptor; however, many patients are non-responsive. METHODS: In this retrospective clinical and genetic study, we identified 1077 adult patients who satisfied the International Classification of Headache Disorders, 3rd edition, criteria for migraine without aura, migraine with aura, or chronic migraine and who were prescribed an anti-CGRP migraine preventive between May 2018 and May 2021. Screening of 558 patients identified 289 with data at baseline and first follow-up visits; data were available for 161 patients at a second follow-up visit. The primary outcome was migraine days per month (MDM). In 198 genotyped patients, we evaluated associations between responders (i.e., patients with ≥50% reduction in MDM at follow-up) and genes involved in CGRP signaling or pharmacological response, and genetic and polygenic risk scores. RESULTS: The median time to first follow-up was 4.4 (0.9-22) months after preventive start. At the second follow-up, 5.7 (0.9-13) months later, 145 patients had continued on the same preventive. Preventives had strong, persistent effects in reducing MDM in responders (follow-up 1: η2 = 0.26, follow-up 2: η2 = 0.22). At the first but not second follow-up: galcanezumab had a larger effect than erenumab, while no difference was seen at either follow-up between galcanezumab and fremanezumab or fremanezumab and erenumab. The decrease in MDM at follow-up was generally proportional to baseline MDM, larger in females, and increased with months on medication. At the first follow-up only, patients with prior hospitalization for migraine or who had not responded to more preventive regimens had a smaller decrease in MDM. Reasons for stopping or switching a preventive varied between medications and were often related to cost and insurance coverage. At both follow-ups, patient tolerance (1: 92.2% [262/284]; 2: 95.2% [141/145]) and continued use (1: 77.5% [224/289]; 2: 80.6% [116/145]) were high and similar across preventives. Response consistency (always non-responders: 31.7% [46/145]; always responders: 56.5% [82/145], and one-time only responders: 11.7% [17/145]) was also similar across preventives. Non-responder status had nominally significant associations with rs12615320-G in RAMP1 (odds ratio [95% confidence interval]: 4.7 [1.5, 14.7]), and rs4680-A in COMT (0.6[0.4, 0.9]). Non-responders had a lower mean genetic risk score than responders (1.0 vs. 1.1; t(df) = -1.75(174.84), p = 0.041), and the fraction of responders increased with genetic and polygenic risk score percentile. CONCLUSIONS: In this real-world setting, anti-CGRP preventives reduced MDM persistently and had similar and large effect sizes on MDM reduction; however, clinical and genetic factors influenced response.


Sujet(s)
Peptide relié au gène de la calcitonine , Migraines , Adulte , Femelle , Humains , Anticorps monoclonaux/pharmacologie , Anticorps monoclonaux/usage thérapeutique , Migraines/traitement médicamenteux , Migraines/génétique , Migraines/prévention et contrôle , Études rétrospectives , Résultat thérapeutique , Mâle
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