RÉSUMÉ
Optical continuous glucose monitoring (CGM) systems are emerging for personalized glucose management owing to their lower cost and prolonged durability compared to conventional electrochemical CGMs. Here, we report a computational CGM system, which integrates a biocompatible phosphorescence-based insertable biosensor and a custom-designed phosphorescence lifetime imager (PLI). This compact and cost-effective PLI is designed to capture phosphorescence lifetime images of an insertable sensor through the skin, where the lifetime of the emitted phosphorescence signal is modulated by the local concentration of glucose. Because this phosphorescence signal has a very long lifetime compared to tissue autofluorescence or excitation leakage processes, it completely bypasses these noise sources by measuring the sensor emission over several tens of microseconds after the excitation light is turned off. The lifetime images acquired through the skin are processed by neural network-based models for misalignment-tolerant inference of glucose levels, accurately revealing normal, low (hypoglycemia) and high (hyperglycemia) concentration ranges. Using a 1 mm thick skin phantom mimicking the optical properties of human skin, we performed in vitro testing of the PLI using glucose-spiked samples, yielding 88.8% inference accuracy, also showing resilience to random and unknown misalignments within a lateral distance of â¼4.7 mm with respect to the position of the insertable sensor underneath the skin phantom. Furthermore, the PLI accurately identified larger lateral misalignments beyond 5 mm, prompting user intervention for realignment. The misalignment-resilient glucose concentration inference capability of this compact and cost-effective PLI makes it an appealing wearable diagnostics tool for real-time tracking of glucose and other biomarkers.
RÉSUMÉ
This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.
RÉSUMÉ
Objective and Impact Statement: Human epidermal growth factor receptor 2 (HER2) is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer (BC) and helps predict its prognosis. Here, we introduce a deep learning-based approach utilizing pyramid sampling for the automated classification of HER2 status in immunohistochemically (IHC) stained BC tissue images. Introduction: Accurate assessment of IHC-stained tissue slides for HER2 expression levels is essential for both treatment guidance and understanding of cancer mechanisms. Nevertheless, the traditional workflow of manual examination by board-certified pathologists encounters challenges, including inter- and intra-observer inconsistency and extended turnaround times. Methods: Our deep learning-based method analyzes morphological features at various spatial scales, efficiently managing the computational load and facilitating a detailed examination of cellular and larger-scale tissue-level details. Results: This approach addresses the tissue heterogeneity of HER2 expression by providing a comprehensive view, leading to a blind testing classification accuracy of 84.70%, on a dataset of 523 core images from tissue microarrays. Conclusion: This automated system, proving reliable as an adjunct pathology tool, has the potential to enhance diagnostic precision and evaluation speed, and might substantially impact cancer treatment planning.
Sujet(s)
Diabète gestationnel , Humains , Femelle , Grossesse , Chine/épidémiologie , Enfant d'âge préscolaire , Enfant , Surpoids/complications , Obésité pédiatrique/complications , Facteurs de risque , Mâle , Hypoglycémiants/usage thérapeutique , Adulte , Effets différés de l'exposition prénatale à des facteurs de risque , Asiatiques/statistiques et données numériques , Indice de masse corporelle , Peuples d'Asie de l'EstRÉSUMÉ
Diffractive deep neural networks (D2NNs) are composed of successive transmissive layers optimized using supervised deep learning to all-optically implement various computational tasks between an input and output field-of-view. Here, we present a pyramid-structured diffractive optical network design (which we term P-D2NN), optimized specifically for unidirectional image magnification and demagnification. In this design, the diffractive layers are pyramidally scaled in alignment with the direction of the image magnification or demagnification. This P-D2NN design creates high-fidelity magnified or demagnified images in only one direction, while inhibiting the image formation in the opposite direction-achieving the desired unidirectional imaging operation using a much smaller number of diffractive degrees of freedom within the optical processor volume. Furthermore, the P-D2NN design maintains its unidirectional image magnification/demagnification functionality across a large band of illumination wavelengths despite being trained with a single wavelength. We also designed a wavelength-multiplexed P-D2NN, where a unidirectional magnifier and a unidirectional demagnifier operate simultaneously in opposite directions, at two distinct illumination wavelengths. Furthermore, we demonstrate that by cascading multiple unidirectional P-D2NN modules, we can achieve higher magnification factors. The efficacy of the P-D2NN architecture was also validated experimentally using terahertz illumination, successfully matching our numerical simulations. P-D2NN offers a physics-inspired strategy for designing task-specific visual processors.
RÉSUMÉ
Gestational diabetes remains the most common medical disorder in pregnancy, with short-term and long-term consequences for mothers and offspring. New insights into pathophysiology and management suggest that the current gestational diabetes treatment approach should expand from a focus on late gestational diabetes to a personalised, integrated life course approach from preconception to postpartum and beyond. Early pregnancy lifestyle intervention could prevent late gestational diabetes. Early gestational diabetes diagnosis and treatment has been shown to be beneficial, especially when identified before 14 weeks of gestation. Early gestational diabetes screening now requires strategies for integration into routine antenatal care, alongside efforts to reduce variation in gestational diabetes care, across settings that differ between, and within, countries. Following gestational diabetes, an oral glucose tolerance test should be performed 6-12 weeks postpartum to assess the glycaemic state. Subsequent regular screening for both dysglycaemia and cardiometabolic disease is recommended, which can be incorporated alongside other family health activities. Diabetes prevention programmes for women with previous gestational diabetes might be enhanced using shared decision making and precision medicine. At all stages in this life course approach, across both high-resource and low-resource settings, a more systematic process for identifying and overcoming barriers to preventative care and treatment is needed to reduce the current global burden of gestational diabetes.
Sujet(s)
Diabète gestationnel , Humains , Diabète gestationnel/diagnostic , Diabète gestationnel/thérapie , Diabète gestationnel/prévention et contrôle , Femelle , Grossesse , Prise en charge prénatale/méthodes , Hyperglycémie provoquée , Dépistage de masseRÉSUMÉ
AIMS: To examine long-term risk of overweight in offspring of women with gestational diabetes mellitus (GDM) defined by the International Association of Diabetes and Pregnancy Study Group (IADPSG)'s criteria but not by the 1999 World Health Organization (WHO)'s criteria. METHODS: We followed up 1681 mother-child pairs for 8 years in Tianjin, China. Overweight in children aged 1-5 and 6-8 were respectively defined as body mass index-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of hyperglycemia indices at oral glucose tolerance test and GDMs defined by different criteria for offspring overweight at different ages. RESULTS: Offspring of women with fasting plasma glucose ≥5.1â¯mmol/L were at increased risk of overweight at 6-8 years old (OR:1.45, 95% CI: 1.09-1.93). GDM defined by the IADPSG's criteria only was associated with increased risk of childhood overweight at 6-8 years old (1.65, 1.13-2.40), as compared with non-GDM by either of the two sets of criteria. CONCLUSIONS: Newly defined GDM by the IADPSG's criteria increased the risk of offspring overweight aged 6-8 years.
Sujet(s)
Marqueurs biologiques , Glycémie , Diabète gestationnel , Hyperglycémie provoquée , Obésité pédiatrique , Humains , Diabète gestationnel/épidémiologie , Diabète gestationnel/diagnostic , Diabète gestationnel/sang , Femelle , Grossesse , Facteurs de risque , Chine/épidémiologie , Enfant , Obésité pédiatrique/épidémiologie , Obésité pédiatrique/diagnostic , Mâle , Glycémie/métabolisme , Enfant d'âge préscolaire , Appréciation des risques , Facteurs temps , Nourrisson , Adulte , Marqueurs biologiques/sang , Effets différés de l'exposition prénatale à des facteurs de risque/épidémiologie , Facteurs âges , Indice de masse corporelle , Organisation mondiale de la santé , Odds ratio , Peuples d'Asie de l'EstRÉSUMÉ
This study aimed to develop and validate a nomogram based on immune checkpoint genes (ICGs) for predicting prognosis and immune checkpoint blockade (ICB) efficacy in lung adenocarcinoma (LUAD) patients. A total of 385 LUAD patients from the TCGA database and 269 LUAD patients in the combined dataset (GSE41272 + GSE50081) were divided into training and validation cohorts, respectively. Three different machine learning algorithms including random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and support vector machine (SVM) were employed to select the predictive markers from 82 ICGs to construct the prognostic nomogram. The X-tile software was used to stratify patients into high- and low-risk subgroups based on the nomogram-derived risk scores. Differences in functional enrichment and immune infiltration between the two subgroups were assessed using gene set variation analysis (GSVA) and various algorithms. Additionally, three lung cancer cohorts receiving ICB therapy were utilized to evaluate the ability of the model to predict ICB efficacy in the real world. Five ICGs were identified as predictive markers across all three machine learning algorithms, leading to the construction of a nomogram with strong potential for prognosis prediction in both the training and validation cohorts (all AUC values close to 0.800). The patients were divided into high- (risk score ≥ 185.0) and low-risk subgroups (risk score < 185.0). Compared to the high-risk subgroup, the low-risk subgroup exhibited enrichment in immune activation pathways and increased infiltration of activated immune cells, such as CD8 + T cells and M1 macrophages (P < 0.05). Furthermore, the low-risk subgroup had a greater likelihood of benefiting from ICB therapy and longer progression-free survival (PFS) than did the high-risk subgroup (P < 0.05) in the two cohorts receiving ICB therapy. A nomogram based on ICGs was constructed and validated to aid in predicting prognosis and ICB treatment efficacy in LUAD patients.
RÉSUMÉ
We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.
Sujet(s)
Tumeurs du cerveau , Glioblastome , Apprentissage machine , Humains , Glioblastome/génétique , Glioblastome/immunologie , Tumeurs du cerveau/génétique , Tumeurs du cerveau/immunologie , Inhibiteur tissulaire de métalloprotéinase-1/génétique , Inhibiteur tissulaire de métalloprotéinase-1/métabolisme , Survivants du cancer , Algorithmes , Nomogrammes , Mâle , Femelle , Transcriptome , Adulte d'âge moyenRÉSUMÉ
Objective:To explore strategies for preserving facial nerve function during surgeries for rare tumors of the internal auditory canal. Methods:A total of 235 cases of internal auditory canal tumors treated between 2010 and 2023 were included, encompassing vestibular schwannomas, cavernous hemangiomas, meningiomas, and other rare tumors. Various data, including clinical presentations, imaging classifications, and treatment processes, were meticulously analyzed to delineate the characteristics of rare tumors and assess pre-and postoperative facial nerve function. Results:Among all internal auditory canal tumors, vestibular schwannomas accounted for 91.9%. In rare tumors, facial nerve schwannomas constituted 5.3%, cavernous hemangiomas 26.3%, meningiomas 15.8%, and arterial aneurysms 10.5%. Significantly, patients with cavernous hemangiomas displayed pronounced invasion of the facial nerve by the tumor, in contrast to other tumor types where clear boundaries with the facial nerve were maintained. During surgery, individualized approaches and strategies for facial nerve protection were implemented for different tumor types, involving intraoperative dissection, tumor excision, and facial nerve reconstruction. Conclusion:Preservation of the facial nerve is crucial in the surgical management of rare tumors of the internal auditory canal. Accurate preoperative diagnosis, appropriate timing of surgery, selective surgical approaches, and meticulous intraoperative techniques can maximize the protection of facial nerve function. Personalized treatment plans and strategies for facial nerve functional reconstruction are anticipated to enhance surgical success rates, reduce the risk of postoperative facial nerve dysfunction, and ultimately improve the quality of life for patients.
Sujet(s)
Nerf facial , Humains , Femelle , Mâle , Nerf facial/chirurgie , Adulte d'âge moyen , Adulte , Sujet âgé , Neurinome de l'acoustique/chirurgie , Méningiome/chirurgie , Oreille interne/chirurgie , Hémangiome caverneux/chirurgie , Tumeurs de l'oreille/chirurgie , Jeune adulte , Adolescent , Tumeurs des méninges/chirurgieRÉSUMÉ
OBJECTIVES: To explore associations between adverse birth outcomes and childhood overweight at 3-8 years of age. DESIGN: A prospective cohort study. SETTING: Six central urban districts of Tianjin, China. PARTICIPANTS: 1681 woman-child pairs. METHODS: 1681 woman-child pairs were followed up for 8 years in Tianjin, China. Demographic and clinical information including birth outcomes was collected longitudinally, commencing from first antenatal care visit till postpartum period. Offspring height and weight were measured at 3-8 years of age. High and low weight/length ratios (WLR) at birth were, respectively, defined as ≥90th and ≤10th gestational week and sex-specific percentiles. Overweight for children at 3-5 and 6-8 years of age were, respectively, defined as body mass index (BMI)-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Binary logistic regression analysis was used to obtain ORs and 95% CI with a stepwise backward selection method to select independent predictors. PRIMARY OUTCOMES MEASURES: Childhood overweight. RESULTS: Of 1681 children, 10.7% (n=179) and 27.8% (n=468) developed overweight at 3-5 and 6-8 years of age, respectively. Large for gestational age (LGA) was associated with increased risk of overweight at 3-5 years of age (aOR: 1.86, 95% CI: 1.27 to 2.72) while high WLR at birth was associated with increased risk of overweight at 6-8 years of age (1.82, 1.41 to 2.34). Low WLR at birth was associated with decreased risk of overweight at 6-8 years of age (0.52, 0.30 to 0.90). CONCLUSIONS: LGA and high WLR at birth predicted childhood overweight at 3-5 and 6-8 years of age, respectively. Low WLR at birth was associated with decreased risk of childhood overweight at 6-8 years of age.
Sujet(s)
Obésité pédiatrique , Complications de la grossesse , Nouveau-né , Mâle , Humains , Grossesse , Femelle , Enfant d'âge préscolaire , Enfant , Obésité pédiatrique/épidémiologie , Obésité pédiatrique/complications , Surpoids/épidémiologie , Surpoids/complications , Poids de naissance , Études prospectives , Prise de poids , Indice de masse corporelle , Chine/épidémiologie , Facteurs de risqueRÉSUMÉ
AIMS: To examine the independent and interactive effects of maternal gestational diabetes mellitus (GDM) and high pre-pregnancy body mass index (BMI) on the risk of offspring adverse growth patterns. MATERIALS AND METHODS: One thousand six hundred and eighty one mother-child pairs were followed for 8 years in Tianjin, China. Group-based trajectory modelling was used to identify offspring growth patterns. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of GDM and high pre-pregnancy BMI for offspring adverse growth patterns. Restricted cubic spline was used to identify cut-off points. Additive interactions and multiplicative interactions were used to test interactive effects between GDM and high pre-pregnancy BMI for adverse growth patterns. RESULTS: Four distinct growth patterns were identified in offspring, including normal growth pattern, persistent lean growth pattern, late obesity growth pattern (LOGP), and persistent obesity growth pattern (POGP). Maternal high pre-pregnancy BMI was associated with LOGP and POGP (adjusted OR, 95% CI: 2.38, 1.74-3.25 & 4.92, 2.26-10.73). GDM greatly enhanced the adjusted OR of high pre-pregnancy BMI for LOGP up to 3.48 (95% CI: 2.25-5.38). Additive interactions and multiplicative interactions between both risk factors were significant for LOGP but not for POGP. CONCLUSIONS: Maternal high pre-pregnancy BMI was associated with increased risk of LOGP and POGP, whereas GDM greatly enhanced the risk of high pre-pregnancy BMI for LOGP.
Sujet(s)
Diabète gestationnel , Grossesse , Femelle , Humains , Indice de masse corporelle , Poids de naissance , Obésité , Facteurs de risqueRÉSUMÉ
BACKGROUND/OBJECTIVE: Previous studies found conflicting results on the association between maternal gestational diabetes mellitus (GDM) and childhood overweight/obesity. This study was to assess the association between maternal GDM and offspring's adiposity risk from 6 to 8 years of age. METHODS: The present study longitudinally followed 1156 mother-child pairs (578 GDM and 578 non-GDM) at 5.9 ± 1.2 years postpartum and retained 912 mother-child pairs (486 GDM and 426 non-GDM) at 8.3 ± 1.6 years postpartum. Childhood body mass index (BMI), waist circumference, body fat and skinfold were measured using standardized methods. RESULTS: Compared with the counterparts born to mothers with normal glucose during pregnancy, children born to mothers with GDM during pregnancy had higher mean values of adiposity indicators (waist circumference, body fat, subscapular skinfold and suprailiac skinfold) at 5.9 and 8.3 years of age. There was a positive association of maternal GDM with changes of childhood adiposity indicators from the 5.9-year to 8.3-year visit, and ß values were significantly larger than zero: +0.10 (95% CI: 0.02-0.18) for z score of BMI for age, +1.46 (95% CI: 0.70-2.22) cm for waist circumference, +1.78% (95% CI: 1.16%-2.40%) for body fat, +2.40 (95% CI: 1.78-3.01) mm for triceps skinfold, +1.59 (95% CI: 1.10-2.09) mm for subscapular skinfold, and +2.03 (95% CI: 1.35-2.71) mm for suprailiac skinfold, respectively. Maternal GDM was associated with higher risks of childhood overweight/obesity, central obesity, and high body fat (Odd ratios 1.41-1.57 at 5.9 years of age and 1.73-2.03 at 8.3 years of age) compared with the children of mothers without GDM. CONCLUSIONS: Maternal GDM was a risk factor of childhood overweight/obesity at both 5.9 and 8.3 years of age, which was independent from several important confounders including maternal pre-pregnancy BMI, gestational weight gain, children's birth weight and lifestyle factors. This significant and positive association became stronger with age.
Sujet(s)
Diabète gestationnel , Obésité pédiatrique , Grossesse , Femelle , Humains , Nourrisson , Enfant , Diabète gestationnel/épidémiologie , Obésité pédiatrique/épidémiologie , Adiposité , Poids de naissance , Indice de masse corporelle , Facteurs de risque , SurpoidsRÉSUMÉ
Aims: This study aimed to explore associations of mannan-binding lectin-associated serine protease (MASP) levels in early pregnancy with gestational diabetes mellitus (GDM). We also examined interactions of MASPs and deoxycholic acid (DCA)/glycoursodeoxycholic acid (GUDCA) for the GDM risk and whether the interactive effects if any on the GDM risk were mediated via lysophosphatidylcholine (LPC) 18:0. Materials and methods: A 1:1 case-control study (n = 414) nested in a prospective cohort of pregnant women was conducted in Tianjin, China. Binary conditional logistic regressions were performed to examine associations of MASPs with the GDM risk. Additive interaction measures were used to examine interactions between MASPs and DCA/GUDCA for the GDM risk. Mediation analyses and Sobel tests were used to examine mediation effects of LPC18:0 between the copresence of MASPs and DCA/GUDCA on the GDM risk. Results: High MASP-2 was independently associated with GDM [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.44-4.77], while the effect of high MASP-1 on GDM was attributable to high MASP-2 (P for Sobel test: 0.003). Low DCA markedly increased the OR of high MASP-2 alone from 2.53 (1.10-5.85) up to 10.6 (4.22-26.4), with a significant additive interaction. In addition, high LPC18:0 played a significant mediating role in the links from low DCA to GDM and from the copresence of high MASP-2 and low DCA to GDM (P for Sobel test <0.001) but not in the link from high MASP-2 to GDM. Conclusions: High MASP-1 and MASP-2 in early pregnancy were associated with GDM in Chinese pregnant women. MASP-2 amplifies the risk of low DCA for GDM, which is mediated via LPC18:0.
Sujet(s)
Diabète gestationnel , Lectine liant le mannose , Humains , Femelle , Grossesse , Mannose-Binding Protein-Associated Serine Proteases/analyse , Diabète gestationnel/épidémiologie , Femmes enceintes , Études cas-témoins , Peuples d'Asie de l'Est , Études prospectivesRÉSUMÉ
In this study, we designed a Pt@KIT-6 nanocomposite prepared by impregnating platinum nanoparticles on the nanopores of the KIT-6 mesoporous material. This Pt@KIT-6 nanocomposite was used as a catalyst in a micro fixed bed reactor (MFBR) for the continuous-flow hydrogenation of halogenated nitroarenes, which demonstrates three advantages. First, the Pt@KIT-6 nanocomposite has a stable mesoporous nanostructure, which effectively enhances the active site and hydrogen adsorption capacity. The uniformly distributed pore structure and large specific surface area were confirmed by electron microscopy and N2 physisorption, respectively. In addition, the aggregation of the loaded metal was avoided, which facilitated the maintenance of high activity and selectivity. The conversion and selectivity reached 99% within 5.0 minutes at room temperature (20 °C). Furthermore, the continuous-flow microreactor allows precise control and timely transfer of the reaction system, reducing the impact of haloid acids. The activity and selectivity of the Pt@KIT-6 nanocomposite showed virtually no degradation after 24 hours of continuous operation of the entire continuous-flow system. Overall, the Pt@KIT-6 nanocomposite showed good catalysis for the hydrogenation of halogenated nitroarenes in the continuous-flow microreactor. This work provides insights into the rational design of a highly active and selective catalyst for selective hydrogenation systems.
RÉSUMÉ
Compartmentalization, leveraging microfluidics, enables highly sensitive assays, but the requirement for significant infrastructure for their design, build, and operation limits access. Multimaterial particle-based technologies thermodynamically stabilize monodisperse droplets as individual reaction compartments with simple liquid handling steps, precluding the need for expensive microfluidic equipment. Here, we further improve the accessibility of this lab on a particle technology to resource-limited settings by combining this assay system with a portable multimodal reader, thus enabling nanoliter droplet assays in an accessible platform. We show the utility of this platform in measuring N-terminal propeptide B-type natriuretic peptide (NT-proBNP), a heart failure biomarker, in complex medium and patient samples. We report a limit of detection of â¼0.05 ng/mL and a linear response between 0.2 and 2 ng/mL in spiked plasma samples. We also show that, owing to the plurality of measurements per sample, "swarm" sensing acquires better statistical quantitation with a portable reader. Monte Carlo simulations show the increasing capability of this platform to differentiate between negative and positive samples, i.e., below or above the clinical cutoff for acute heart failure (â¼0.1 ng/mL), as a function of the number of particles measured. Our platform measurements correlate with gold standard ELISA measurement in cardiac patient samples, and achieve lower variation in measurement across samples compared to the standard well plate-based ELISA. Thus, we show the capabilities of a cost-effective droplet-reader system in accurately measuring biomarkers in nanoliter droplets for diseases that disproportionately affect underserved communities in resource-limited settings.
Sujet(s)
Défaillance cardiaque , Microfluidique , Humains , Marqueurs biologiques/analyse , Vasodilatateurs , Test ELISA , Défaillance cardiaque/diagnosticRÉSUMÉ
BACKGROUND: To estimate associations of sulfur-containing amino acids (SAAs) in the early trimester of pregnancy and gestational diabetes mellitus (GDM) and estimate associations of maternal SAAs with adverse growth patterns in offspring. METHODS: We established a 1:1 matched case-control study (n = 486) from our cohort of pregnant women, and 401 children were followed up at ages 1 to 8 years. We conducted binary conditional logistic regression to estimate the risk associations of serum SAAs with GDM. Multinomial logistic regression was implemented to explore associations of maternal SAAs with adverse growth patterns in the offspring. RESULTS: High serum methionine and cystine were independently associated with increased GDM risk (OR: 1.92, 95%CI: 1.18-3.13 and 2.69, 1.59-4.53). Conversely, a low level of serum taurine was independently associated with increased GDM risk (2.61, 1.64-4.16). Maternal high cystine and low taurine were also associated with an increased risk of persistent obesity growth pattern (POGP) in offspring (OR: 2.79, 95%CI: 1.09-7.17 and 3.92, 1.11-13.89) and the effect was largely independent of GDM. CONCLUSIONS: High serum methionine, cystine and low serum taurine in the early trimester of pregnancy were associated with a greatly increased risk of GDM. Maternal high cystine and low taurine were associated with elevated risk of offspring POGP, largely independent of GDM.
RÉSUMÉ
Under spatially coherent light, a diffractive optical network composed of structured surfaces can be designed to perform any arbitrary complex-valued linear transformation between its input and output fields-of-view (FOVs) if the total number (N) of optimizable phase-only diffractive features is ≥~2NiNo, where Ni and No refer to the number of useful pixels at the input and the output FOVs, respectively. Here we report the design of a spatially incoherent diffractive optical processor that can approximate any arbitrary linear transformation in time-averaged intensity between its input and output FOVs. Under spatially incoherent monochromatic light, the spatially varying intensity point spread function (H) of a diffractive network, corresponding to a given, arbitrarily-selected linear intensity transformation, can be written as H(m, n; m', n') = |h(m, n; m', n')|2, where h is the spatially coherent point spread function of the same diffractive network, and (m, n) and (m', n') define the coordinates of the output and input FOVs, respectively. Using numerical simulations and deep learning, supervised through examples of input-output profiles, we demonstrate that a spatially incoherent diffractive network can be trained to all-optically perform any arbitrary linear intensity transformation between its input and output if N ≥ ~2NiNo. We also report the design of spatially incoherent diffractive networks for linear processing of intensity information at multiple illumination wavelengths, operating simultaneously. Finally, we numerically demonstrate a diffractive network design that performs all-optical classification of handwritten digits under spatially incoherent illumination, achieving a test accuracy of >95%. Spatially incoherent diffractive networks will be broadly useful for designing all-optical visual processors that can work under natural light.
RÉSUMÉ
BACKGROUND AND AIMS: To explore association of serum hyaluronidase 1 (HYAL1) level in early pregnancy with gestational diabetes mellitus (GDM), and to examine interactive effects of HYAL1 with ceramides species on GDM risk. MATERIALS AND METHODS: We conducted a 1:1 matched case-control study (n = 414) of pregnant women from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10th gestational weeks). Binary conditional logistic regression and restricted cubic spline (RCS) analysis were used to examine full-range risk association between HYAL1 and GDM. Additive interactions and multiplicative interactions were employed to test interactive effects of HYAL1 with ceramides species on GDM risk. RESULTS: Ln HYAL1 was linearly associated with GDM risk and the adjusted OR of HYAL1 ≥ vs. < its median for GDM was significant (1.65, 95%CI: 1.08-2.52). High HYAL1 markedly enhanced the ORs of high ceramide 18:0 for GDM from 2.31 (1.06-5.01) to 6.74 (2.85-16.0), and low ceramide 24:0 from 3.08 (1.33-7.11) to 8.15 (3.03-21.9), with significant additive interactions. CONCLUSIONS: High HYAL1 in early pregnancy may increase the risk of GDM in Chinese women, possibly via enhancing the effects of high ceramide 18:0 and low ceramide 24:0 on GDM risk.