PathGPS: discover shared genetic architecture using GWAS summary data.

The increasing availability and scale of biobanks and "omic" datasets bring new horizons for understanding biological mechanisms. PathGPS is an exploratory data analysis tool to discover genetic architectures using Genome Wide Association Studies (GWAS) summary data. PathGPS is based on a linear structural equation model where traits are regulated by both genetic and environmental pathways. PathGPS decouples the genetic and environmental components by contrasting the GWAS associations of "signal" genes with those of "noise" genes. From the estimated genetic component, PathGPS then extracts genetic pathways via principal component and factor analysis, leveraging the low-rank and sparse properties. In addition, we provide a bootstrap aggregating ("bagging") algorithm to improve stability under data perturbation and hyperparameter tuning. When applied to a metabolomics dataset and the UK Biobank, PathGPS confirms several known gene-trait clusters and suggests multiple new hypotheses for future investigations.

Paeonol attenuates Substance P-induced urticaria by inhibiting Src kinase phosphorylation in mast cells.

BACKGROUND: Treatment of chronic urticaria is challenging, the discovery of effective therapeutic drugs is urgently in demand. PURPOSE: To study the effect and mechanism of Paeonol targeting mast cells and its therapeutic effect on chronic urticaria. STUDY DESIGN: We developed a chronic urticaria model in vivo and mast cell model in vitro examined the effect of Paeonol in the treatment of chronic urticaria and its mechanism of action in mast cells. METHOD: The anti-anaphylactoid effect of Paeonol was evaluated in PCA and systemic anaphylaxis models. The treatment role of Paeonol was studied in urticaria model. The release of cytokines and chemokines was measured using enzyme immunoassay kits. Western blot analysis was conducted to investigate phosphorylation of Src, PI3K, and PLC. In vitro kinase assays were conducted to investigate the kinase activity of Lyn, PLC, PI3K and Src. RESULTS: In our study, Paeonol was able to attenuate evans blue leakage, serum histamine and chemokine release in a passive skin allergic reaction model. Simultaneously, Paeonol inhibited vasodilation and mast cell degranulation in C57BL/6 mice. Further research found that Paeonol alleviated symptoms such as erythema and rash in the Substance P-induced urticaria model, this is accompanied by inhibiting the release of related inflammatory factors. Validation experiments on mast cells in vitro found that Paeonol inhibited the activation of Src-PI3K/Lyn-PLC-NF-κB signaling pathway by crosslinking with Src kinase. Moreover, calcium influx, mast cell degranulation, cytokines generation and chemotaxis were reduced in LAD2 cells. Molecular docking experiments revealed that Paeonol is a specific antagonist targeting Src kinase in the treatment of skin diseases such as urticaria. CONCLUSION: Paeonol, a herb-derived phenolic compound, can provide drug candidate for developing new drug in treatment of skin disease such as urticaria. SIGNIFICANCE STATEMENT: In this study, we primarily examined the effect of Paeonol in the treatment of chronic urticaria and its mechanism of action in mast cells. Interestingly, Paeonol was found to regulate Src kinase activity downstream of MRGPRX2 triggered signaling cascade in mast cells. Therefore, this plant-derived phenolic compound may provide a therapeutic option for the treatment of chronic urticaria.

Graphene nanoplatelet/cellulose acetate film with enhanced antistatic, thermal dissipative and mechanical properties for packaging.

With the increased concern over environment protection, cellulose acetate (CA) has drawn great interests as an alternative for packaging material due to its biodegradability and abundant resources; whereas, the poor antistatic property and thermal conductivity restrict its application in packaging. In this work, we proposed a simple but effective strategy to produce high performance graphene nanoplatelet (GNP)/CA composite films via the consecutive homogenization and solvent casting processes. Relying on the spontaneous absorption of CA during homogenization, the GNP/CA produced shows an excellent dispersibility in the N,N-Dimethylformamide (DMF) solution and many fewer structural defects compared with GNPs alone. As a result, the composite films obtained exhibit simultaneously and significantly enhanced antistatic, heat dissipative and mechanical properties compared with CA. Specifically, the GNP/CA composite with the optimal formula has promising overall performances (namely, surface resistivity of 3.33 × 107 Ω/sq, in-plane thermal conductivity of 5.359 W ( m · K ) , out-of-plane thermal conductivity of 0.785 W ( m · K ) , and tensile strength of 37.1 MPa). Featured by its promising overall properties, simple production processes and biodegradability, the as-prepared GNP/CA composite film shows a great potential for application in packaging. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-023-05155-2.

Robot-assisted all-epiphyseal anterior cruciate ligament reconstruction in skeletally immature patients: a retrospective study.

PURPOSE: To review a series of adolescent patients with anterior cruciate ligament (ACL) injuries surgically treated with robot-assisted all-epiphyseal ACL reconstruction (ACLR), and to compare with the traditional freehand group. METHODS: This retrospective clinical study included 16 patients with ACL injuries who underwent ACLR by robot-assisted technique or traditional freehand method from June 2018 to March 2020. All patients were divided into the robot-assisted group (6 patients) or the traditional surgery group (10 patients). The number of intra-operative fluoroscopies, operation time, accuracy of bone tunnel insertions, International Knee Documentation Committee (IKDC) subjective score and ligament laxity testing were recorded in the two groups. RESULTS: All patients returned for follow-up, at a mean of 31.6 ± 4.5 months after surgery. The average age of the robot-assisted group was 12.2 ± 1.3 years. The number of intra-operative fluoroscopies was 10.9 ± 2.8 in the traditional freehand group, whereas it was only 3.0 ± 0.6 in the robot-assisted group, which was significantly lower (P < 0.05). The operative time in the robot-assisted group was shorter than that in the traditional freehand group (87 ± 10.7 min vs. 126 ± 12.1 min, P < 0.05). The distance between the center of actual insertion and the center of the idea insertion on both femoral and tibial intra-articular bone tunnel were 1.5 ± 0.3 mm and 1.6 ± 0.3 mm for the robot-assisted group and 2.7 mm ± 0.4 mm and 2.4 ± 0.4 mm for the traditional freehand group (P < 0.05). There were no significant differences between the two groups in function recovery at the last follow-up. CONCLUSIONS: All-epiphyseal ACLR is a technically demanding procedure with a small margin of error. Robot-assisted treatment of ACL injuries in skeletally immature patients is more accurate than traditional freehand method, with shorter operation time and fewer intra-operative fluoroscopies.

Vessel segmentation for X-ray coronary angiography using ensemble methods with deep learning and filter-based features.

BACKGROUND: Automated segmentation of coronary arteries is a crucial step for computer-aided coronary artery disease (CAD) diagnosis and treatment planning. Correct delineation of the coronary artery is challenging in X-ray coronary angiography (XCA) due to the low signal-to-noise ratio and confounding background structures. METHODS: A novel ensemble framework for coronary artery segmentation in XCA images is proposed, which utilizes deep learning and filter-based features to construct models using the gradient boosting decision tree (GBDT) and deep forest classifiers. The proposed method was trained and tested on 130 XCA images. For each pixel of interest in the XCA images, a 37-dimensional feature vector was constructed based on (1) the statistics of multi-scale filtering responses in the morphological, spatial, and frequency domains; and (2) the feature maps obtained from trained deep neural networks. The performance of these models was compared with those of common deep neural networks on metrics including precision, sensitivity, specificity, F1 score, AUROC (the area under the receiver operating characteristic curve), and IoU (intersection over union). RESULTS: With hybrid under-sampling methods, the best performing GBDT model achieved a mean F1 score of 0.874, AUROC of 0.947, sensitivity of 0.902, and specificity of 0.992; while the best performing deep forest model obtained a mean F1 score of 0.867, AUROC of 0.95, sensitivity of 0.867, and specificity of 0.993. Compared with the evaluated deep neural networks, both models had better or comparable performance for all evaluated metrics with lower standard deviations over the test images. CONCLUSIONS: The proposed feature-based ensemble method outperformed common deep convolutional neural networks in most performance metrics while yielding more consistent results. Such a method can be used to facilitate the assessment of stenosis and improve the quality of care in patients with CAD.

Changes in Hyoid Bone Position Before and After Distraction Osteogenesis in Infants With Robin Sequence.

PURPOSE: To study the changes of hyoid position in infants with Robin sequence before and after mandibular distraction osteogenesis, and to explore the related factors. MATERIAL AND METHODS: Twenty-six infants with Robin sequence underwent bilateral mandibular distraction osteogenesis from May 2016 to April 2020. Three-dimensional computed tomography data of patients before and after surgery were analyzed with Materialise Mimics 17.0. Changes in the three-dimensional position of the hyoid bone were studied. RESULTS: The angle between the long axis of the tongue body and hard palate plane, and the angle between the long axis of the tongue body and mandibular plane were significantly decreased after surgery than before surgery. The hyoid bone-cranial base vertical distance, hyoid bone-mental point distance, and hyoid bone - epiglottis distance were significantly increased after surgery. The differences in the above-mentioned data were statistically significant ( P  < 0.05). Changes in the angle between the long axis of the tongue body and the hyoid bone - mental point line correlated with changes in the position of the hyoid bone relative to the cervical spine ( P   =  0.006). Postoperatively, the hyoid bone moved forward and the increase in the hyoid bone - mental point osseous distance interval (41.28%) was significantly greater than the increase in the hyoid bone-epiglottis distance (18.73%). Differences in the total mandibular length and the hyoid bone - cranial base vertical distance are related to the age at the operation ( P  < 0.05). The younger the age at the time of surgical intervention, the greater the difference before and after surgery for the same follow-up interval. CONCLUSIONS: The three-dimensional direction of the hyoid bone changes after the distraction osteogenesis of the mandible, and the hyoid bone moves downward and forward. Because the mandibular length and airway changed, the relative positions of the long axis of the tongue body on the sagittal plane rotated clockwise.

Assessment of heterogeneous treatment effect estimation accuracy via matching.

We study the assessment of the accuracy of heterogeneous treatment effect (HTE) estimation, where the HTE is not directly observable so standard computation of prediction errors is not applicable. To tackle the difficulty, we propose an assessment approach by constructing pseudo-observations of the HTE based on matching. Our contributions are three-fold: first, we introduce a novel matching distance derived from proximity scores in random forests; second, we formulate the matching problem as an average minimum-cost flow problem and provide an efficient algorithm; third, we propose a match-then-split principle for the assessment with cross-validation. We demonstrate the efficacy of the assessment approach using simulations and a real dataset.

Role of glucocorticoid signaling in exercise-associated changes in high-fat diet preference in rats.

The simultaneous introduction of wheel running (WR) and diet choice (high-carbohydrate chow vs. high-fat diet) results in sex-specific diet choice patterns in rats. WR induces a high-fat (HF) diet avoidance, and such avoidance persists in the majority of males, but not females, throughout a 2-wk period. Exercise is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates glucocorticoid (GC) release, which can alter dietary preferences. Here, we examined the role of the HPA axis and GC signaling in mediating exercise-induced changes in diet preference and the associated neurobiological adaptations that may underlie sex differences in diet choice patterns. Experiment 1 revealed that adrenalectomy did not significantly alter the initiation and persistence of running-induced HF diet avoidance in male rats. Experiment 2 showed that acute WR resulted in greater neural activation than chronic WR in the medial prefrontal (mPFC) and insular cortices (IC) in male rats. Experiment 3 revealed sex differences in the molecular adaptation to exercise and diet preference. First, exercise increased gene expression of fkbp5 in the mPFC, IC, and hippocampus of WR females but had limited influence in males. Second, male and female WR rats that reversed or maintained HF diet avoidance showed distinct sex- and HF diet preference-dependent expression profiles of genes involved in cortical GC signaling (e.g., nr3c1, nr3c2, and src1). Taken together, our results suggest sex differences in region-specific neural adaptations may underlie sex differences in diet preference and the health benefits from exercise.

Comprehensive lipidomic profiling in serum and multiple tissues from a mouse model of diabetes.

INTRODUCTION: Diabetes mellitus is a serious metabolic disorder causing multiple organ damage in human. However, the lipidomic profiles in different organs and their associations are rarely studied in either diabetic patients or animals. OBJECTIVES: To evaluate and compare the characteristics of lipid species in serum and multiple tissues in a diabetic mouse model. METHODS: Semi-quantitative profiling analyses of intact and oxidized lipids were performed in serum and multiple tissues from a diabetic mouse model fed a high fat diet and treated with streptozotocin by using LC/HRMS and MS/MS. The total content of each lipid class, and the tissue-specific lipid species in all tissue samples were determined and compared by multivariate analyses. RESULTS: The diabetic mouse model displayed characteristic differences in serum and multiple organs: the brain and heart showed the largest reduction in cardiolipin, while the kidney had more alterations in triacylglycerol. Interestingly, the lipidomic differences also existed between different regions of the same organ: cardiolipin species with highly polyunsaturated fatty acyls decreased only in atrium but not in ventricle, while renal cortex showed longer fatty acyl chains for both increased and decreased triacylglycerol species than renal medulla. Importantly, diabetes caused an accumulation of lipid hydroperoxides, suggesting that oxidative stress was induced in all organs except for the brain during the development of diabetes. CONCLUSIONS: These findings provided novel insight into the organ-specific relationship between diabetes and lipid metabolism, which might be useful for evaluating not only diabetic tissue injury but also the effectiveness of diabetic treatments.

Synthesis and Self-Assembly Behavior of Chlorophyll Derivatives for Ratiometric Photoacoustic Signal Optimization.

Self-assembly provides researchers powerful tools for creating ordered functional structures and complex architectures. Investigation of in vivo self-assembly reveals the assembly/aggregation-induced retention (AIR) effect and enhanced targeting effect, which can be applied to promising biomedical applications by enhancing molecular accumulation in the target region. These unique bioeffects inspire the interest of researchers in construction of self-assembled nanomaterials in biological systems. Although many efforts have been achieved, the in-depth analysis of the relationship between assemblies and functions is rarely reported. Here, we focus on the relationship of chlorophyll-derivative assemblies and their photoacoustic signals and attempt to establish a method for monitoring the aggregation efficiency in vivo based on photoacoustic signals. Three arginine-rich peptide-purpurin molecules were designed and synthesized. The assembled capabilities and assembly processes of these molecules were characterized and monitored by UV, fluorescence, and CD spectra images of gradually changing polarities in mixed solvents, and the morphologies of the assemblies were observed by TEM. Furthermore, the relationship between the aggregation ratios of the molecules and the ratiometric photoacoustic signals was systemically studied. We prospect that the fundamental research in revealing objective laws will be useful for future guidance in optimizing photoacoustic detection windows and assembled molecule design.

A Novel Geometric Morphometric Analytical Method for Classifying Mandibular Morphology in Infants With Isolated Pierre Robin Sequence.

PURPOSE: There is a lack of uniformity in the diagnostic criteria and system for the morphologic classification of micrognathia in infants with isolated Pierre Robin sequence (IPRS). Therefore, the aim of this study was to create a morphologic classification system for IPRS-affected mandibles that may guide surgical management and osteotomy design. PATIENTS AND METHODS: We designed and implemented a retrospective cross-sectional study. The study sample included infants with IPRS. The predictor variables included shape variables of the IPRS-affected mandibles. The outcome of interest was morphologic differences among the IPRS-affected mandibles in the infancy stage. The original coordinate data of the mandibular images were analyzed by a generalized Procrustes analysis and 2-block partial least squares analysis to identify the focal and nonfocal areas in the IPRS-affected mandibles. The original feature points were modified according to the results of 2-block partial least squares analysis. The modified feature points were further analyzed by principal component analysis, K-means cluster analysis, and canonical variate analysis to obtain a morphologic classification of the IPRS-affected mandibles. RESULTS: One hundred fifty infants with IPRS were enrolled in this study. Principal component analysis showed that the variations among IPRS-affected mandibles were mostly in terms of the shapes of the mandibular ramus, mandibular body, and angle of the mandible. On the basis of the results of K-means cluster analysis and canonical variate analysis, the mandibles in group A3 showed characteristics such as a simply shorter mandibular body. Group B3 was adjusted to show characteristics such as a shorter mandibular body with a more obtuse mandibular angle, whereas group C3 showed characteristics such as a shorter mandibular body with a shorter mandibular ramus. CONCLUSIONS: Our study confirmed the hypothesis that there are quantifiable morphologic differences among the IPRS-affected mandibles, and it provided a morphologic classification of the IPRS-affected mandibles that will help to promote the clinical diagnosis and treatment.

Andrographolide inhibits secretagogue-induced pseudo-allergic reaction.

Many kinds of drugs induce pseudo-allergic reactions due to activation of mast cells. We investigated the anti-pseudo-allergic effect of andrographolide (Andro). The effects of Andro on pseudo-allergic reactions were investigated in vivo and in vitro. Andro suppressed compound 48/80 (C48/80) induced pseudo-allergic reactions in mice in a dose-dependent manner. Andro also inhibited C48/80-induced local inflammatory reactions in mice. In vitro studies revealed that Andro reduced C48/80-induced mast cells degranulation. Human phospho-kinase array kit and western blotting showed that Andro could inhibit pseudo-allergic responses via the calcium signaling pathway.

Neohesperidin suppresses IgE-mediated anaphylactic reactions and mast cell activation via Lyn-PLC-Ca2+ pathway.

Mast cells play an essential role in IgE-FcεR1-mediated allergic diseases. Citrus aurantium is a prolific source of flavonoids with various biological activities, including anti-inflammatory, antioxidant, and anti-tumor efficacies. Neohesperidin is a novel flavonoid isolated from the leaves of C. aurantium. In this study, the anti-allergic and anti-inflammatory potentials of neohesperidin were investigated along with its molecular mechanism. The anti-anaphylactic activity of neohesperidin was evaluated through hind paw extravasation study in mice. Calcium imaging was used to assess intracellular Ca2+ mobilization. The levels of cytokines and chemokines were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. Neohesperidin suppressed IgE-induced mast cell activations, including degranulation and secretion of cytokines and eicosanoids through inhibiting phosphorylation of Lyn kinase. Neohesperidin inhibited the release of histamine and other proinflammatory cytokines through a mast cell-dependent passive cutaneous anaphylaxis animal model. Histological studies demonstrated that neohesperidin substantially inhibited IgE-induced cellular infiltration and attenuated mast cell activation in skin tissue. In conclusion, our study revealed that neohesperidin could inhibit allergic responses in vivo and in vitro, and the molecule may be regarded as a novel agent for preventing mast cell-immediate and delayed allergic diseases.

Mivacurium induce mast cell activation and pseudo-allergic reactions via MAS-related G protein coupled receptor-X2.

BACKGROUND: Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children. METHODS: MAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. RESULTS: Mivacurium caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, MrgprB2-knockout mice displayed no inflammatory response to mivacurium. Mivacurium induced LAD2 cell degranulation in a dose-dependent manner. Mivacurium stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. However, mivacurium induced the release of only low levels of mediators in LAD2 cells transfected with MRGPRX2-targeted small interfering (si)RNA. Notably, cytokine release was not observed in LAD2 cells even when stimulated with high concentrations of mivacurium. CONCLUSION: Mivacurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. However, mivacurium did not induce the release of other cytokines. Therefore, the targeting of MRGPRX2 can potentially block mivacurium-induced adverse drug effects, particularly pseudo-allergic reactions.

Astrocytic N-Myc Downstream-regulated Gene-2 Is Involved in Nuclear Transcription Factor κB-mediated Inflammation Induced by Global Cerebral Ischemia.

BACKGROUND: Inflammation is a key element in the pathophysiology of cerebral ischemia. This study investigated the role of N-Myc downstream-regulated gene-2 in nuclear transcription factor κB-mediated inflammation in ischemia models. METHODS: Mice (n = 6 to 12) with or without nuclear transcription factor κB inhibitor pyrrolidinedithiocarbamate pretreatment were subjected to global cerebral ischemia for 20 min. Pure astrocyte cultures or astrocyte-neuron cocultures (n = 6) with or without pyrrolidinedithiocarbamate pretreatment were exposed to oxygen-glucose deprivation for 4 h or 2 h. Astrocytic nuclear transcription factor κB and N-Myc downstream-regulated gene-2 expression, proinflammatory cytokine secretion, neuronal apoptosis and survival, and memory function were analyzed at different time points after reperfusion or reoxygenation. Proinflammatory cytokine secretion was also studied in lentivirus-transfected astrocyte lines after reoxygenation. RESULTS: Astrocytic nuclear transcription factor κB and N-Myc downstream-regulated gene-2 expression and proinflammatory cytokine secretion increased after reperfusion or reoxygenation. Pyrrolidinedithiocarbamate pretreatment significantly reduced N-Myc downstream-regulated gene-2 expression and proinflammatory cytokine secretion in vivo and in vitro, reduced neuronal apoptosis induced by global cerebral ischemia/reperfusion (from 65 ± 4% to 47 ± 4%, P = 0.0375) and oxygen-glucose deprivation/reoxygenation (from 45.6 ± 0.2% to 22.0 ± 4.0%, P < 0.001), and improved memory function in comparison to vehicle-treated control animals subjected to global cerebral ischemia/reperfusion. N-Myc downstream-regulated gene-2 lentiviral knockdown reduced the oxygen-glucose deprivation-induced secretion of proinflammatory cytokines. CONCLUSIONS: Astrocytic N-Myc downstream-regulated gene-2 is up-regulated after cerebral ischemia and is involved in nuclear transcription factor κB-mediated inflammation. Pyrrolidinedithiocarbamate alleviates ischemia-induced neuronal injury and hippocampal-dependent cognitive impairment by inhibiting increases in N-Myc downstream-regulated gene-2 expression and N-Myc downstream-regulated gene-2-mediated inflammation.

Repression of neuronal nitric oxide (nNOS) synthesis by MTA1 is involved in oxidative stress-induced neuronal damage.

The Metastasis-associated protein 1 (MTA1) coregulator, an essential component of the nucleosome remodeling and deacetylase (NuRD) complex, potentiates neuroprotective effects against ischemia/reperfusion (I/R) injury. But the underlying mechanism(s) remain largely unknown. Here, we discovered that neuronal MTA1 was a target of oxidative stress, and stimulation of neurons with oxygen glucose deprivation (OGD) treatment significantly inhibited MTA1 expression. Additionally, MTA1 depletion augmented ischemic oxidative stress and thus promoted oxidative stress-induced neuronal cell death by OGD. While studying the impact of MTA1 status on global neuronal gene expression, we unexpectedly discovered that MTA1 may modulate OGD-induced neuronal damage via regulation of distinct nitric oxide synthase (NOS) (namely neuronal NOS, nNOS) signaling. We provided in vitro evidence that NOS1 is a chromatin target of MTA1 in OGD-insulted neurons. Mechanistically, neuronal ischemia-mediated repression of NOS1 expression is accompanied by the enhanced recruitment of MTA1 along with histone deacetylases (HDACs) to the NOS1 promoter, which could be effectively blocked by a pharmacological inhibitor of the HDACs. These findings collectively reveal a previously unrecognized, critical homeostatic role of MTA1, both as a target and as a component of the neuronal oxidative stress, in the regulation of acute neuronal responses against brain I/R damage. Our study also provides a molecular mechanistic explanation for the previously reported neurovascular protection by selective nNOS inhibitors.

Association between systemic immunity-inflammation index and sex hormones in children and adolescents aged 6-19.

Objectives: This study aimed to evaluate the relationship between systemic immune-inflammation index (SII) and sex hormones in children and adolescents aged 6-19 years. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Inclusion criteria comprised subjects aged 6-19 years with complete data on both SII and sex hormones. We employed weighted multiple regression analysis and subgroup analytical methods to independently estimate the relationship between SII and sex hormones. Results: In this study, a total of 3767 participants were included, with an average age of 12.32 ± 3.95 years. Males constituted 50.54%, and females 49.46%. Among males, a statistically significant negative correlation emerged between SII and sex hormone-binding globulin (SHBG). Similarly, in the female population, SII exhibited a statistically significant negative correlation with total testosterone (TT), SHBG, and the Ratio of TT to estradiol, while maintaining a positive correlation with free androgen index (FAI). Subgroup analysis underscored variances in the association between sex hormones and SII within cohorts distinguished by pubertal status or different body mass index (BMI). In addition, the relationship between SII and estradiol exhibited nonlinearity. Employing a two-segment linear regression model, we identified an inverted U-shaped association between SII and estradiol, with an inflection point of 748.09 (1000cell/ml). Conclusion: Our findings suggest that SII may be an independent risk factor for changes in sex hormones in both male and female children and adolescents. More prospective and experimental studies should be conducted to validate our results and elucidate the underlying molecular pathways.

Leveraging Multi-Annotator Label Uncertainties as Privileged Information for Acute Respiratory Distress Syndrome Detection in Chest X-ray Images.

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening lung injury for which early diagnosis and evidence-based treatment can improve patient outcomes. Chest X-rays (CXRs) play a crucial role in the identification of ARDS; however, their interpretation can be difficult due to non-specific radiological features, uncertainty in disease staging, and inter-rater variability among clinical experts, thus leading to prominent label noise issues. To address these challenges, this study proposes a novel approach that leverages label uncertainty from multiple annotators to enhance ARDS detection in CXR images. Label uncertainty information is encoded and supplied to the model as privileged information, a form of information exclusively available during the training stage and not during inference. By incorporating the Transfer and Marginalized (TRAM) network and effective knowledge transfer mechanisms, the detection model achieved a mean testing AUROC of 0.850, an AUPRC of 0.868, and an F1 score of 0.797. After removing equivocal testing cases, the model attained an AUROC of 0.973, an AUPRC of 0.971, and an F1 score of 0.921. As a new approach to addressing label noise in medical image analysis, the proposed model has shown superiority compared to the original TRAM, Confusion Estimation, and mean-aggregated label training. The overall findings highlight the effectiveness of the proposed methods in addressing label noise in CXRs for ARDS detection, with potential for use in other medical imaging domains that encounter similar challenges.

hydroSIM: super-resolution speckle illumination microscopy with a hydrogel diffuser.

Super-resolution microscopy has emerged as an indispensable methodology for probing the intricacies of cellular biology. Structured illumination microscopy (SIM), in particular, offers an advantageous balance of spatial and temporal resolution, allowing for visualizing cellular processes with minimal disruption to biological specimens. However, the broader adoption of SIM remains hampered by the complexity of instrumentation and alignment. Here, we introduce speckle-illumination super-resolution microscopy using hydrogel diffusers (hydroSIM). The study utilizes the high scattering and optical transmissive properties of hydrogel materials and realizes a remarkably simplified approach to plug-in super-resolution imaging via a common epi-fluorescence platform. We demonstrate the hydroSIM system using various phantom and biological samples, and the results exhibited effective 3D resolution doubling, optical sectioning, and high contrast. We foresee hydroSIM, a cost-effective, biocompatible, and user-accessible super-resolution methodology, to significantly advance a wide range of biomedical imaging and applications.

Comparison of Low-Frequency or High-Frequency Electrical Acupoint Stimulation on Hypotension After Spinal Anesthesia in Parturients: A Prospective Randomized Controlled Clinical Trial.

Objective: To investigate whether transcutaneous electrical acupoint stimulation (TEAS) at PC6 could reduce hypotension after spinal anesthesia (SA) in parturients and to compare the effect of TEAS at different frequencies. Methods: From February 20, 2023, to August 29, 2023, 90 parturients scheduled for c-section under SA were randomly assigned to receive no treatment (Control), TEAS at high frequency (TEAS-HF), or TEAS at low frequency (TEAS-LF). Treatments started immediately after SA and lasted for 30 min. The primary endpoint was incidence of hypotension by 30 min after SA. Secondary endpoints included lowest systolic blood pressure (SBP) during 30 min after SA, dose of ephedrine, dose of atropine, Apgar score at 1 min, and adverse events, including nausea, vomiting, dizziness, dyspnea, and chest congestion. Results: In the TEAS-HF group, the incidence of hypotension by 30 min after SA was lower (13.3%) than in the Control (53.3%, p = 0.001; OR 1.9, 95% confidence interval [CI]: 1.2-2.8) and TEAS-LF group (40.0%, p = 0.02, OR 1.4, 95% CI: 1.0-2.0). The lowest SBP during 30 min after SA was higher in the TEAS-HF group (100.0 ± 9.4 mm Hg) than in the Control group (91.5 ± 16.5 mm Hg) and TEAS-LF group (93.9 ± 16.6 mm Hg). Patients who received TEAS showed a lower score of nausea and vomiting (both p = 0.02). Patients in the group TEAS-HF showed a lower incidence of dizziness, dyspnea, and of chest congestion than those in the other two groups. There was no difference with respect to atropine consumption and neonatal Apgar score. Conclusions: TEAS-HF at PC6 reduced hypotension after SA in parturients, while TEAS-LF did not. Trial registration: ClinicalTrials.gov (NCT05724095).