Generalizability of Deep Adult Lung Segmentation Models to the Pediatric Population: A Retrospective Study

Lung segmentation in chest X-rays (CXRs) is an important prerequisite for improving the specificity of diagnoses of cardiopulmonary diseases in a clinical decision support system. Current deep learning (DL) models for lung segmentation are trained and evaluated on CXR datasets in which the radiographic projections are captured predominantly from the adult population. However, the shape of the lungs is reported to be significantly different for pediatrics across the developmental stages from infancy to adulthood. This might result in age-related data domain shifts that would adversely impact lung segmentation performance when the models trained on the adult population are deployed for pediatric lung segmentation. In this work, our goal is to analyze the generalizability of deep adult lung segmentation models to the pediatric population and improve performance through a systematic combinatorial approach consisting of CXR modality-specific weight initializations, stacked generalization, and an ensemble of the stacked generalization models. Novel evaluation metrics consisting of Mean Lung Contour Distance and Average Hash Score are proposed in addition to the Multi-scale Structural Similarity Index Measure, Intersection of Union, and Dice metrics to evaluate segmentation performance. We observed a significant improvement (p < 0.05) in cross-domain generalization through our combinatorial approach. This study could serve as a paradigm to analyze the cross-domain generalizability of deep segmentation models for other medical imaging modalities and applications.Comment: 11 pages, 7 figures, and 8 table

Uncovering the effects of model initialization on deep model generalization: A study with adult and pediatric Chest X-ray images

Model initialization techniques are vital for improving the performance and reliability of deep learning models in medical computer vision applications. While much literature exists on non-medical images, the impacts on medical images, particularly chest X-rays (CXRs) are less understood. Addressing this gap, our study explores three deep model initialization techniques: Cold-start, Warm-start, and Shrink and Perturb start, focusing on adult and pediatric populations. We specifically focus on scenarios with periodically arriving data for training, thereby embracing the real-world scenarios of ongoing data influx and the need for model updates. We evaluate these models for generalizability against external adult and pediatric CXR datasets. We also propose novel ensemble methods: F-score-weighted Sequential Least-Squares Quadratic Programming (F-SLSQP) and Attention-Guided Ensembles with Learnable Fuzzy Softmax to aggregate weight parameters from multiple models to capitalize on their collective knowledge and complementary representations. We perform statistical significance tests with 95% confidence intervals and p-values to analyze model performance. Our evaluations indicate models initialized with ImageNet-pre-trained weights demonstrate superior generalizability over randomly initialized counterparts, contradicting some findings for non-medical images. Notably, ImageNet-pretrained models exhibit consistent performance during internal and external testing across different training scenarios. Weight-level ensembles of these models show significantly higher recall (p<0.05) during testing compared to individual models. Thus, our study accentuates the benefits of ImageNet-pretrained weight initialization, especially when used with weight-level ensembles, for creating robust and generalizable deep learning solutions.Comment: 40 pages, 8 tables, 7 figures, 3 supplementary figures and 4 supplementary table

A Modified Laminotomy for Interlaminar Endoscopic Lumbar Discectomy: Technical Report and Preliminary Results

Objective To introduce a technique of laminotomy using a common trephine to enlarge the interlaminar space at L4/5 segment for interlaminar endoscopic lumbar discectomy (IELD) and report the anatomical basis of this procedure, technical details, as well as primary clinical outcomes of a consecutive patient cohort with L4/5 lumbar disc herniation (LDH). Methods On anteroposterior fluoroscopy, the intersection of the medial edge of the inferior articular process and the inferior endplate of L4 vertebra was taken as the target. Using a common trephine, laminotomy was performed to remove a big portion of the posterior wall of the canal under the guidance of endoscopy. From June 2018 to December 2021, the consecutive patients who underwent L4/5 IELD were prospectively studied. Clinical outcomes were assessed at the day before surgery, 1 day, 1 month, 3 months, 12 months after surgery, and the last follow-up. Numerical Rating Scale, Roland-Morris Disability Questionnaire (RMDQ), and MacNab criteria were used to evaluate back and leg pain, the quality of life, and clinical efficacy, respectively. Results There were 64 men and 44 women, with an age of 50.3 ± 14.9 years. The operating time was 74.54 ± 17.42 minutes. The mean follow-up time was 32.7 ± 18.6 months (range, 12–64 months). The complications of IELD included numbness, neck pain, and recurrence. Both leg pain (6.2 ± 1.9 vs. 1.8 ± 0.8, p < 0.001) and back pain (3.1 ± 2.3 vs. 1.7 ± 0.9, p < 0.001) quickly improved after this procedure and maintained (1.1 ± 1.5, 1.1 ± 1.3) at final follow-up. Physical disability due to back pain, as assessed using RMDQ, was improved remarkably after surgery (15.0 ± 5.8 vs. 2.9 ± 4.1, p < 0.001). In addition, MacNab outcome grade was evaluated as good-to-excellent in 96 cases (88.9%). Conclusion A convenient technique of laminotomy using a common trephine was proposed for the L4/5 IELD. It can efficiently enlarge the interlaminar entry to perform endoscopic discectomy. This procedure is particularly suitable for treating LDH with concomitant lumbar spinal stenosis and migrated herniated disc

Research Progress on Bioactivity and Mechanism of Tea Polyphenols

Tea polyphenols are a class of polyphenolic mixtures with phenolic hydroxyl structure in tea plants, which are the main functional component of tea, and the content is relatively high in green tea. Tea polyphenol bioactivity research gains popularity, in the functional food, drug development, preservation and preservation of preservatives and other areas with broad application prospects. Tea polyphenols have a variety of biological activities such as antioxidant, anticancer, hypolipidemic, blood sugar regulation, antibacterial, anti-radiation and so on. Their mechanism of action mainly includes regulating protein kinase B (AKT), nuclear factor-kappa B (NF-κB), epithelial growth factor receptor (EGFR), adenylate activated protein kinase (AMPK) and other signalling pathways and related proteins. By analyzing the relevant research literature in recent years, we review the material properties, biological activities, mechanisms and applications of tea polyphenols, with a view to providing reference for the development of tea polyphenol-containing functional foods and natural medicines

Transient Receptor Potential V Channels Are Essential for Glucose Sensing by Aldolase and AMPK

Fructose-1,6-bisphosphate (FBP) aldolase links sensing of declining glucose availability to AMPK activation via the lysosomal pathway. However, how aldolase transmits lack of occupancy by FBP to AMPK activation remains unclear. Here, we show that FBP-unoccupied aldolase interacts with and inhibits endoplasmic reticulum (ER)-localized transient receptor potential channel subfamily V, inhibiting calcium release in low glucose. The decrease of calcium at contact sites between ER and lysosome renders the inhibited TRPV accessible to bind the lysosomal v-ATPase that then recruits AXIN:LKB1 to activate AMPK independently of AMP. Genetic depletion of TRPVs blocks glucose starvation-induced AMPK activation in cells and liver of mice, and in nematodes, indicative of physical requirement of TRPVs. Pharmacological inhibition of TRPVs activates AMPK and elevates NAD(+) levels in aged muscles, rejuvenating the animals' running capacity. Our study elucidates that TRPVs relay the FBP-free status of aldolase to the reconfiguration of v-ATPase, leading to AMPK activation in low glucose

A Transcriptomic Taxonomy of Mouse Brain-Wide Spinal Projecting Neurons

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for ‘gain setting’ of brain–spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions

Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK

葡萄糖是生物中最基本、最主要的营养物质，它不仅是机体能量的主要来源，也是生物质合成的主要原料。因此，葡萄糖的水平对于生物体是极其重要的。然而，在生活中，体内葡萄糖水平的波动是十分常见的，这是因为我们不可能每时每刻都在摄入葡萄糖：睡一大觉、剧烈运动几个小时或者太忙了没时间吃饭，都会引起葡萄糖水平的显著下降。这时，机体能够触发一套有效的过程应对这类“不利情况”，其中最为关键的就是激活“代谢的核心调节”——AMPK。在葡萄糖水平下降时，被激活的AMPK能够迅速启动脂肪、蛋白质的分解代谢，关闭它们的合成代谢，从而起到维持机体的能量和物质代谢的平衡，弥补机体因葡萄糖不足引起的胁迫压力。那么，机体如何感受葡萄糖水平下降，并“传递”给AMPK使其激活呢？林圣彩教授课题组的这项研究正是发现了生理状态下机体感受葡萄糖水平的机制。通过研究他们发现，无论在不含葡萄糖的细胞培养条件下，还是在饥饿的低血糖的动物体内，都不能观测到AMP水平的上升，这充分说明了机体有一套尚不为人知的、独立于AMP的感应葡萄糖水平的机制。在进一步的研究中他们揭示了这一完整过程：葡萄糖水平下降将引起的葡萄糖代谢中间物——果糖1,6-二磷酸（fructose-1,6-bisphosphate）水平的下降，该过程进一步地被糖酵解通路上的代谢酶——醛缩酶（aldolase）感应，因为醛缩酶正是将含有6个碳原子的果糖1,6-二磷酸裂解成三碳糖的酶，一旦醛缩酶“吃不到”由葡萄糖衍生的果糖1,6-二磷酸，它便“翻脸”，传递给也正是林圣彩教授课题组先前发现的溶酶体途径进而激活AMPK。该过程完全不涉及AMP水平，即能量水平的变化，是一条全新的、完全建立在实际的生理情况上的通路。林圣彩教授进一步地把葡萄糖水平总结为一种“状态信号”，以区别于传统的“能量信号”。据悉，该葡萄糖感知通路的发现对开发用于治疗肥胖症，乃至延长寿命的药物具有深远的意义。【Abstract】The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)1, but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK2, 3, 4, 5. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation6, 7. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.D.G.H. was supported by an Investigator Award from the Wellcome Trust (097726) and a Programme Grant from Cancer Research UK (C37030/A15101). S.-C.L. was supported by grants from the National Key Research and Development Project of China (2016YFA0502001) and the National Natural Science Foundation of China (#31430094, #31690101, #31571214, #31601152 and #J1310027)