Sensitive and isotopic interference-free analysis of Sb using hydride generation-microwave plasma torch-mass spectrometry under ambient condition.

A sensitive and isotopic interference-free analysis method for Sb was developed based on hydride generation-microwave plasma torch-mass spectrometry (HG-MPT-MS). Compared to the conventional ICP-MS, MPT coupled to an ion trap mass spectrometer enabled much "softer" ionization of Sb under ambient condition, which provided multi-detection modes and various ion forms, such as Sb+, SbO+, SbO2-, SbO++H2O and so on. These ion formations can be easily regulated by tuning capillary voltage and tube lens voltage, which facilitated elimination of isotopic interference during analysis, for instance the interference of 123Te on 123Sb could be effectively excluded by optimizing parameters of capillary voltage and tube lens voltage. The potential application of HG-MPT-MS for Sb isotope ratio analysis was also demonstrated, which could be determined in different forms, e.g., 123Sb/121Sb or 123Sb16O/121Sb16O. The value of 123Sb/121Sb was determined to be 0.75110 ± 0.00038 (2σ, n > 50). In addition, the detection limit, linearity and spike recovery were also studied. Overall, HG-MPT-MS performed equally well on detection limit (0.05 µg/L) with ICP-MS or HG-AFS. The linearity (R2 = 0.998) was checked in the concentration range of 10-500 µg/L. Spike recovery were evaluated with two soil samples, and the obtained spike recovery ranged 90-100 %. In general, HG-MPT-MS was expected to be a versatile tool for study the biochemical or geochemical behaviors of Sb and other hydride forming elements under ambient condition in a much simpler and more efficient way.

The Role of Spinal Cord Compression in Predicting Intraoperative Neurophysiological Monitoring Events in Patients With Kyphotic Deformity: A Magnetic Resonance Imaging-Based Study.

OBJECTIVE: To establish a novel classification system for predicting the risk of intraoperative neurophysiological monitoring (IONM) events in surgically-treated patients with kyphotic deformity. METHODS: Patients with kyphotic deformity who underwent surgical correction of cervicothoracic, thoracic, or thoracolumbar kyphosis in our center from July 2005 to December 2020 were recruited. We proposed a classification system to describe the morphology of the spinal cord on T2-weighted sagittal magnetic resonance imaging: type A, circular/symmetric cord with visible cerebrospinal fluid (CSF) between the cord and vertebral body; type B, circular/oval/symmetric cord with no visible CSF between the cord and vertebral body; type C, spinal cord that is fattened/deformed by the vertebral body, with no visible CSF between the cord and vertebral body. Furthermore, based on type C, the spinal cord compression ratio (CR) < 50% was defined as the subtype C-, while the spinal cord CR ≥ 50% was defined as the subtype C+. IONM event was documented, and a comparative analysis was made to evaluate the prevalence of IONM events among patients with diverse spinal cord types. RESULTS: A total of 294 patients were reviewed, including 73 in type A; 153 in type B; 53 in subtype C- and 15 in subtype C+. Lower extremity transcranial motor-evoked potentials and/or somatosensory evoked potentials were lost intraoperatively in 41 cases (13.9%), among which 4 patients with type C showed no return of spinal cord monitoring data. The 14 subtype C+ patients (93.3%) had IONM events. Univariate logistic regression analysis showed that patients with a type C spinal cord (subtype C-: odds ratio [OR], 10.390; 95% confidence interval [CI], 2.215-48.735; p = 0.003; subtype C+, OR, 497.000; 95% CI, 42.126- 5,863.611; p < 0.001) are at significantly higher risk of a positive IONM event during deformity correction compared to those with a type A. In further multiple logistic regression analysis, the spinal cord classification (OR, 5.371; 95% CI, 2.966-9.727; p < 0.001) was confirmed as an independent risk factor for IONM events. CONCLUSION: We presented a new spinal cord classification system based on the relative position of the spinal cord and vertebrae to predict the risk of IONM events in patients with kyphotic deformity. In patients with type C spinal cord, especially those in C+ cases, it is essential to be aware of potential IONM events, and adopt standard operating procedures to facilitate neurological recovery.

Presence of compensatory curve predicts postoperative curve progression in congenital scoliosis after thoracolumbar hemivertebra resection and short fusion.

PURPOSE: To investigate the impact of preoperative compensatory curve on the postoperative curve progression in congenital scoliosis (CS) patients following thoracolumbar hemivertebra (HV) resection and short fusion. METHODS: This study retrospectively reviewed a consecutive cohort of patients with CS who underwent thoracolumbar HV resection and short fusion with a minimum of 2 years follow-up. According to the preoperative curve pattern, patients were divided into compensatory curve group non-compensatory curve group. Based on the postoperative coronal curve evolution, patients were further divided into the progressed group (Group P, with curve decompensation ≥ 20°) and the non-progressed group (Group NP, characterized by well-compensated curves). RESULTS: A total of 127 patients were included in this study, with 31 patients in the compensatory curve group and 96 patients in the non-compensatory curve group. The incidence of postoperative coronal curve progression was significantly higher in the compensatory curve group than that in non-compensatory curve group (35.5% vs. 13.5%, p = 0.007). In the compensatory curve group, patients who experienced postoperative curve progression showed fewer fusion segments (p = 0.001), greater preoperative UIV translation (p = 0.006), greater preoperative LIV tilt (p = 0.017), and larger postoperative UIV tilt (p < 0.001) compared with patients in group NP. Multiple logistic regression demonstrated that the shorter fusion segments and greater postoperative UIV tilt were two independent risk factors for postoperative curve progression. CONCLUSION: The presence of the compensatory curve was associated with a higher incidence of postoperative curve progression in patients with CS who underwent thoracolumbar HV resection and short fusion. Shorter fusion segments and greater postoperative UIV tilt were found to be the risk factors for postoperative curve progression.

TrajVis: a visual clinical decision support system to translate artificial intelligence trajectory models in the precision management of chronic kidney disease.

OBJECTIVE: Our objective is to develop and validate TrajVis, an interactive tool that assists clinicians in using artificial intelligence (AI) models to leverage patients' longitudinal electronic medical records (EMRs) for personalized precision management of chronic disease progression. MATERIALS AND METHODS: We first perform requirement analysis with clinicians and data scientists to determine the visual analytics tasks of the TrajVis system as well as its design and functionalities. A graph AI model for chronic kidney disease (CKD) trajectory inference named DisEase PrOgression Trajectory (DEPOT) is used for system development and demonstration. TrajVis is implemented as a full-stack web application with synthetic EMR data derived from the Atrium Health Wake Forest Baptist Translational Data Warehouse and the Indiana Network for Patient Care research database. A case study with a nephrologist and a user experience survey of clinicians and data scientists are conducted to evaluate the TrajVis system. RESULTS: The TrajVis clinical information system is composed of 4 panels: the Patient View for demographic and clinical information, the Trajectory View to visualize the DEPOT-derived CKD trajectories in latent space, the Clinical Indicator View to elucidate longitudinal patterns of clinical features and interpret DEPOT predictions, and the Analysis View to demonstrate personal CKD progression trajectories. System evaluations suggest that TrajVis supports clinicians in summarizing clinical data, identifying individualized risk predictors, and visualizing patient disease progression trajectories, overcoming the barriers of AI implementation in healthcare. DISCUSSION: The TrajVis system provides a novel visualization solution which is complimentary to other risk estimators such as the Kidney Failure Risk Equations. CONCLUSION: TrajVis bridges the gap between the fast-growing AI/ML modeling and the clinical use of such models for personalized and precision management of chronic diseases.

Sagittal Imbalance in Degenerative Kyphosis: Prevalence and Implication on Postoperative Mechanical Failure.

BACKGROUND AND OBJECTIVES: To explore the patterns of sagittal imbalance in patients with lumbar or thoracolumbar degenerative kyphosis (DK) and determine its implication for the risk of mechanical complication (MC) after corrective surgery. METHODS: A total of 137 patients with DK who underwent corrective surgery were reviewed. The patients were divided into L group (with a kyphotic apex at L2 and below) and TL group (with kyphotic apex at L1 and above). Then, sacral slope (SS) (defined as S1 if SS > 0 in TL, or SS > 10 in L group) and sagittal vertical axis ≥ 5 cm (defined as +) were used as modifier sagittal balance. The Scoliosis Research Society (SRS)-22 questionnaire scores were analyzed, and the risk of mechanical failure was compared across groups. RESULTS: The distribution of subgroups was 38 (27.7%) in TLS1(-) group, 36 (26.3%) in TLS1(+) group, 16 (11.7%) in TLS0(-) group, and 5 (3.6%) in TLS0(+) group. For L group, the figure was 5 (3.6%) in LS1(-), 22 (16.1%) in LS1(+), 7 (5.2%) in LS0(-), and 8 (5.8%) in LS0(+). Patients in L group had significantly higher regional kyphosis, lower lumbar lordosis, and higher sagittal vertical axis, indicating a higher risk of global decompensation. The SRS function scores and pain scores were also lower in the L group compared with the TL group. At a minimum of 2 years of follow-up, χ2 test showed that the incidence of TLS0 (+), LS0 (-), and LS0 (+) had significantly higher rates of MC (>40%). In both TL and L groups, patients with MC were found to have significantly lower bone mineral density than those without. CONCLUSION: The findings decipher the distinct patterns of sagittal imbalance in severe DK patients with kyphotic apex at thoracolumbar or lumbar spine. Patients with kyphotic apex apex at L2 or below, low SS, and global imbalance showed the highest risk of postoperative mechanical failure.

xSiGra: Explainable model for single-cell spatial data elucidation.

Recent advancements in spatial imaging technologies have revolutionized the acquisition of high-resolution multi-channel images, gene expressions, and spatial locations at the single-cell level. Our study introduces xSiGra, an interpretable graph-based AI model, designed to elucidate interpretable features of identified spatial cell types, by harnessing multi-modal features from spatial imaging technologies. By constructing a spatial cellular graph with immunohistology images and gene expression as node attributes, xSiGra employs hybrid graph transformer models to delineate spatial cell types. Additionally, xSiGra integrates a novel variant of Grad-CAM component to uncover interpretable features, including pivotal genes and cells for various cell types, thereby facilitating deeper biological insights from spatial data. Through rigorous benchmarking against existing methods, xSiGra demonstrates superior performance across diverse spatial imaging datasets. Application of xSiGra on a lung tumor slice unveils the importance score of cells, illustrating that cellular activity is not solely determined by itself but also impacted by neighboring cells. Moreover, leveraging the identified interpretable genes, xSiGra reveals endothelial cell subset interacting with tumor cells, indicating its heterogeneous underlying mechanisms within the complex cellular communications.

Preoperative supine pelvic incidence predicts standing pelvic incidence following S2AI fixation in patients with adult spinal deformity: a prospective study.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the PI change in different postures and before and after S2­alar­iliac (S2AI) screw fixation, and to investigate whether pre-op supine PI could predict post-op standing PI. Previous studies have reported PI may change with various positions. Some authors postulated that the unexpected PI change in ASD patients could be due to sacroiliac joint laxity, S2-alar-iliac (S2AI) screw placement, or aggressive sagittal cantilever technique. However, there was a lack of investigation on how to predict post-op standing PI when making surgical strategy. METHODS: A prospective case series of ASD patients undergoing surgical correction with S2AI screw placement was conducted. Full-spine X-ray films were obtained at pre-op standing, pre-op supine, pre-op prone, as well as post-op standing postures. Pelvic parameters were measured. Spearman correlation analysis was used to determine relationships between each parameter. RESULTS: A total of 83 patients (22 males, 61females) with a mean age of 58.4 ± 9.5 years were included in this study. Pre-op standing PI was significantly lower than post-op standing PI (p = 0.004). Pre-op prone PI was significantly lower than post-op standing PI (p = 0.001). By contrast, no significant difference was observed between pre-op supine and post-op standing PI (p = 0.359) with a mean absolute difference of 2.2° ± 1.9°. Correlation analysis showed supine PI was significantly correlated with post-op standing PI (r = 0.951, p < 0.001). CONCLUSION: This study revealed the PI changed after S2AI screw fixation. The pre-op supine PI can predict post-op standing PI precisely, which facilitates to provide correction surgery strategy with a good reference for ideal sagittal alignment postoperatively.

Potential impairment of spinal cord around the apical vertebral level in hyperkyphotic patients: findings from diffusion tensor imaging.

PURPOSE: To evaluate the neuronal metrics/microstructure of the spinal cord around apical region in patients with hyperkyphosis using diffusion tensor imaging (DTI). METHODS: Thirty-seven patients with hyperkyphosis aged 45.5 ± 19.6 years old who underwent 3.0 T magnetic resonance imaging (MRI) examination with DTI sequence were prospectively enrolled from July 2022 to July 2023. Patients were divided into three groups according to spinal cord/ cerebrospinal fluid (CSF) architecture on sagittal-T2 MRI of the thoracic apex (the axial spinal cord classification): Group A-circular cord with visible CSF, Group B-circular cord without visible CSF at apical dorsal, and Group C-spinal cord deformed without intervening CSF. The fractional anisotropy (FA) values acquired from DTI were compared among different groups. Correlations between DTI parameters and global kyphosis (GK)/sagittal deformity angular ratio (sagittal DAR) were evaluated using Pearson correlation coefficients. RESULTS: In all patients, FA values were significantly lower at apical level as compared with those at one level above or below the apex (0.548 ± 0.070 vs. 0.627 ± 0.056 versus 0.624 ± 0.039, P < 0.001). At the apical level, FA values were significantly lower in Group C than those in Group B (0.501 ± 0.052 vs. 0.598 ± 0.061, P < 0.001) and Group A (0.501 ± 0.052 vs. 0.597 ± 0.019, P < 0.001). Moreover, FA values were significantly lower in symptomatic group than those in non-symptomatic group (0.498 ± 0.049 v. 0.578 ± 0.065, P < 0.001). Pearson correlation analysis showed that GK (r2 = 0.3945, P < 0.001) and sagittal DAR (r2 = 0.3079, P < 0.001) were significantly correlation with FA values at apical level. CONCLUSION: In patients with hyperkyphosis, the FA of spinal cord at apical level was associated with the neuronal metrics/microstructure of the spinal cord. Furthermore, the DTI parameter of FA at apical level was associated with GK and sagittal DAR.

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis.

OBJECTIVE: Low bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover. METHODS: A total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X-ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score < -1, and the normal (NOR) group if the Z score ≥ -1 SD compared to the healthy control. For the 16S rRNA sequencing, the raw reads were filtered to remove low-quality reads, and operational taxonomic units were identified with the Uparse program. Weighted UniFrac distance matrix for the beta-diversity metrics and principal coordinate analysis (PCoA) was performed, and the statistical comparisons were made with permutational multivariate analysis of variance (PERMANOVA) and analysis of similarity (ANONISM). Linear discriminant analysis effect size (LEfSe) was used to identify the enriched species in two groups. The "Random forest" was applied to determine the optimal biomarker for OPN according to the mean decrease in Gini value. The metabolic function was predicted by the Tax4Fun analysis. The Pearson correlation coefficient was used to evaluate the associations between GM species, bone turnover markers, and BMD. RESULTS: The serum ß-CTX was increased in the OPN group (n = 67) compared to the NOR group (n = 59). Patients in OPN groups showed significantly decreased α diversity indicated by the Shannon index. Principal coordinate analysis (PCoA) analysis showed significant clustering of GM between OPN and NOR groups. At genus level, the Escherichia-Shigella and Faecalibacterium were significantly enriched in the OPN group compared to that in the NOR group (p < 0.05), whereas the abundance of Prevotella was significantly decreased (p = 0.0012). The relative abundance of Megamonas and Prevotella was positively correlated with the femur BMD. The abundance of Escherichia-Shigella was negatively correlated with femur BMD and positively correlated with serum ß-CTX levels. Functional analysis revealed significant differences in starch and sucrose metabolism, pyruvate and cysteine, and methionine metabolism between NOR and OPN groups. CONCLUSION: The alterations of GM in AIS patients are correlated with osteopenia. The association between enriched species, BMD, and bone turnover markers provides novel diagnostic and therapeutic targets for the clinical management of AIS.

Tumor-Targeting Multiple Metabolic Regulations for Bursting Antitumor Efficacy of Chemodynamic Therapy.

Interfering with intratumoral metabolic processes is proven to effectively sensitize different antitumor treatments. Here, a tumor-targeting catalytic nanoplatform (CQ@MIL-GOX@PB) loading with autophagy inhibitor (chloroquine, CQ) and glucose oxidase (GOX) is fabricated to interfere with the metabolisms of tumor cells and tumor-associated macrophages (TAMs), then realizing effective antitumor chemodynamic therapy (CDT). Once accumulating in the tumor site with the navigation of external biotin, CQ@MIL-GOX@PB will release Fe ions and CQ in the acid lysosomes of tumor cells, the latter can sensitize Fe ions-involved antitumor CDT by blocking the autophagy-dependent cell repair. Meanwhile, the GOX component will consume glucose, which not only generates many H2O2 for CDT but also once again decelerates the tumor repair process by reducing energy metabolism. What is more, the release of CQ can also drive the NO anabolism of TAMs to further sensitize CDT. This strategy of multiple metabolic regulations is evidenced to significantly improve the antitumor effect of traditional CDT nanoagents and might provide a new sight to overcome the bottlenecks of different antitumor treatments.

SpaRx: elucidate single-cell spatial heterogeneity of drug responses for personalized treatment.

Spatial cellular authors heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies such as CosMx, MERSCOPE and Xenium delineate the spatial gene expression patterns at the single cell resolution. This provides unprecedented opportunities to identify spatially localized cellular resistance and to optimize the treatment for individual patients. In this work, we present a graph-based domain adaptation model, SpaRx, to reveal the heterogeneity of spatial cellular response to drugs. SpaRx transfers the knowledge from pharmacogenomics profiles to single-cell spatial transcriptomics data, through hybrid learning with dynamic adversarial adaption. Comprehensive benchmarking demonstrates the superior and robust performance of SpaRx at different dropout rates, noise levels and transcriptomics coverage. Further application of SpaRx to the state-of-the-art single-cell spatial transcriptomics data reveals that tumor cells in different locations of a tumor lesion present heterogenous sensitivity or resistance to drugs. Moreover, resistant tumor cells interact with themselves or the surrounding constituents to form an ecosystem for drug resistance. Collectively, SpaRx characterizes the spatial therapeutic variability, unveils the molecular mechanisms underpinning drug resistance and identifies personalized drug targets and effective drug combinations.

SiGra: single-cell spatial elucidation through an image-augmented graph transformer.

Recent advances in high-throughput molecular imaging have pushed spatial transcriptomics technologies to subcellular resolution, which surpasses the limitations of both single-cell RNA-seq and array-based spatial profiling. The multichannel immunohistochemistry images in such data provide rich information on the cell types, functions, and morphologies of cellular compartments. In this work, we developed a method, single-cell spatial elucidation through image-augmented Graph transformer (SiGra), to leverage such imaging information for revealing spatial domains and enhancing substantially sparse and noisy transcriptomics data. SiGra applies hybrid graph transformers over a single-cell spatial graph. SiGra outperforms state-of-the-art methods on both single-cell and spot-level spatial transcriptomics data from complex tissues. The inclusion of immunohistochemistry images improves the model performance by 37% (95% CI: 27-50%). SiGra improves the characterization of intratumor heterogeneity and intercellular communication and recovers the known microscopic anatomy. Overall, SiGra effectively integrates different spatial modality data to gain deep insights into spatial cellular ecosystems.

SpaRx: Elucidate single-cell spatial heterogeneity of drug responses for personalized treatment.

Spatial cellular heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies such as CosMx SMI, MERSCOPE, and Xenium delineate the spatial gene expression patterns at the single cell resolution. This provides unprecedented opportunities to identify spatially localized cellular resistance and to optimize the treatment for individual patients. In this work, we present a graph-based domain adaptation model, SpaRx, to reveal the heterogeneity of spatial cellular response to drugs. SpaRx transfers the knowledge from pharmacogenomics profiles to single-cell spatial transcriptomics data, through hybrid learning with dynamic adversarial adaption. Comprehensive benchmarking demonstrates the superior and robust performance of SpaRx at different dropout rates, noise levels, and transcriptomics coverage. Further application of SpaRx to the state-of-art single-cell spatial transcriptomics data reveals that tumor cells in different locations of a tumor lesion present heterogenous sensitivity or resistance to drugs. Moreover, resistant tumor cells interact with themselves or the surrounding constituents to form an ecosystem for drug resistance. Collectively, SpaRx characterizes the spatial therapeutic variability, unveils the molecular mechanisms underpinning drug resistance, and identifies personalized drug targets and effective drug combinations. Key Points: We have developed a novel graph-based domain adaption model named SpaRx, to reveal the heterogeneity of spatial cellular response to different types of drugs, which bridges the gap between pharmacogenomics knowledgebase and single-cell spatial transcriptomics data.SpaRx is developed tailored for single-cell spatial transcriptomics data and is provided available as a ready-to-use open-source software, which demonstrates high accuracy and robust performance.SpaRx uncovers that tumor cells located in different areas within tumor lesion exhibit varying levels of sensitivity or resistance to drugs. Moreover, SpaRx reveals that tumor cells interact with themselves and the surrounding microenvironment to form an ecosystem capable of drug resistance.

Enhanced ultrasonic spray ionization for direct mass spectrometry analysis of aqueous solution and complex samples using a single-orifice piezoelectric atomizer.

An efficient and superior soft ionization approach for direct mass spectrometry analysis of a variety of samples such as aqueous solution, raw biological sample and proteins, was developed based on commercially available piezoelectric atomizers. A single conical orifice (5 µm in diameter) was created on the atomizer, which resulted in generation of uniform fine droplets and long-duration of MS signal. The two electrodes of piezoelectric atomizer were connected to the two sides of ceramic ring which was insulated from the metallic substrate. The unique design allowed an additional high voltage input towards the spray reagents, which facilitated direct analysis of more complex samples without sample pre-treatment, such as biological samples (tomato tissue). The ionization was driven by an extremely low electrical power (3.5 V rechargeable battery) yet providing an efficient and superior soft ionization. The method displayed a better thermal and pH stability than nano electrospray ionization (nanoESI) and electrospray ionization (ESI) on direct analysis of Vitamin B and protein aqueous solutions. Quantitative analysis of Vitamin B and Rhodamine B aqueous solutions was also investigated, showing a good linearity (R2 > 0.99). In addition, our results suggested that compared with ESI and nanoESI, the method not only could be used for direct analysis of intact protein, but also provide more information concerning the association between intact protein and the subunits.

spaCI: deciphering spatial cellular communications through adaptive graph model.

Cell-cell communications are vital for biological signalling and play important roles in complex diseases. Recent advances in single-cell spatial transcriptomics (SCST) technologies allow examining the spatial cell communication landscapes and hold the promise for disentangling the complex ligand-receptor (L-R) interactions across cells. However, due to frequent dropout events and noisy signals in SCST data, it is challenging and lack of effective and tailored methods to accurately infer cellular communications. Herein, to decipher the cell-to-cell communications from SCST profiles, we propose a novel adaptive graph model with attention mechanisms named spaCI. spaCI incorporates both spatial locations and gene expression profiles of cells to identify the active L-R signalling axis across neighbouring cells. Through benchmarking with currently available methods, spaCI shows superior performance on both simulation data and real SCST datasets. Furthermore, spaCI is able to identify the upstream transcriptional factors mediating the active L-R interactions. For biological insights, we have applied spaCI to the seqFISH+ data of mouse cortex and the NanoString CosMx Spatial Molecular Imager (SMI) data of non-small cell lung cancer samples. spaCI reveals the hidden L-R interactions from the sparse seqFISH+ data, meanwhile identifies the inconspicuous L-R interactions including THBS1-ITGB1 between fibroblast and tumours in NanoString CosMx SMI data. spaCI further reveals that SMAD3 plays an important role in regulating the crosstalk between fibroblasts and tumours, which contributes to the prognosis of lung cancer patients. Collectively, spaCI addresses the challenges in interrogating SCST data for gaining insights into the underlying cellular communications, thus facilitates the discoveries of disease mechanisms, effective biomarkers and therapeutic targets.

Feature Selection for Unsupervised Machine Learning.

Compared to supervised machine learning (ML), the development of feature selection for unsupervised ML is far behind. To address this issue, the current research proposes a stepwise feature selection approach for clustering methods with a specification to the Gaussian mixture model (GMM) and the k-means. Rather than the existing GMM and k-means which are carried out based on all the features, the proposed method selects a subset of features to implement the two methods, respectively. The research finds that a better result can be obtained if the existing GMM and k-means methods are modified by nice initializations. Experiments based on Monte Carlo simulations show that the proposed method is more computationally efficient and the result is more accurate than the existing GMM and k-means methods based on all the features. The experiment based on a real-world dataset confirms this finding.

Surgical Treatment for Severe Cervical Hyperlordosis and Thoracolumar Kyphoscoliosis with Emery-Dreifuss Muscular Dystrophy: A Case Report and Literature Review.

BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) is an uncommon, gradually progressive X-linked myopathy, and it could result in rigid spinal deformity. Only a few case reports have described surgical treatment of cervical hyperlordosis and thoracolumbar kyphoscoliosis secondary to EDMD. We report a rare case of EDMD to present the surgical strategies of severe cervical hyperlordosis and thoracolumbar kyphoscoliosis. CASE PRESENTATION: The patient was a 22-year-old man with EDMD who had severe cervical hyperlordosis and thoracolumbar kyphoscoliosis. A posterior spinal fusion from T9-S2 was performed to correct the thoracolumbar kyphoscoliosis at the age of 21 years. Six months later, with an anterior C7-T1 closing wedge bone-disc-bone osteotomy and a posterior-anterior-posterior cervicothoracic fusion from C4-T4, the cervical deformity was corrected, thus achieving a horizontal gaze. During 1.5-year follow-up, no loss of correction was observed. CONCLUSION: Cervical posterior-anterior-posterior closing-wedge osteotomy combined with long fusion at thoracolumbar spine can be a reliable surgical technique to correct severe spine deformity in EDMD. This two-stage revision surgical strategy can help restore a horizontal gaze on the basis of a balanced trunk. Cervical deformity in such patients should be corrected in the first stage considering its role as a "driver" of the global spine deformity.

Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system.

Omega-3 polyunsaturated fatty acids (PUFAs) can play important roles in maintaining mental health and resistance to stress, and omega-3 PUFAs supplementation can display beneficial effects on both the prevention and treatment of depressive disorders. Although the underlying mechanisms are still unclear, accumulated evidence indicates that omega-3 PUFAs can exhibit pleiotropic effects on the neural structure and function. Thus, they play fundamental roles in brain activities involved in the mood regulation. Since depressive symptoms have been assumed to be of central origin, this review aims to summarize the recently published studies to identify the potential neurobiological mechanisms underlying the anti-depressant effects of omega-3 PUFAs. These include that of (1) anti-neuroinflammatory; (2) hypothalamus-pituitary-adrenal (HPA) axis; (3) anti-oxidative stress; (4) anti-neurodegeneration; (5) neuroplasticity and synaptic plasticity; and (6) modulation of neurotransmitter systems. Despite many lines of evidence have hinted that these mechanisms may co-exist and work in concert to produce anti-depressive effects, the potentially multiple sites of action of omega-3 PUFAs need to be fully established. We also discussed the limitations of current studies and suggest future directions for preclinical and translational research in this field.

Dynamic change of pelvic incidence after long fusion to pelvis with S2-alar-iliac screw: a 2-year follow-up study.

INTRODUCTION: Pelvic incidence (PI) is a key morphological parameter that reflects the relation between the sacrum and iliac wings. It is well accepted that PI remains constant after reaching maturity. However, recent studies indicated that PI might be altered after lumbosacral fusion. Additionally, it remains uncertain on the long-term influence of long fusion to pelvis with S2-alar-iliac screw on PI in patients with adult spinal deformity (ASD). STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate whether and how PI would change during the follow-up in ASD patients who underwent S2AI fixation and to identify factors associated with the change in PI. METHODS: We retrospectively reviewed all ASD patients who underwent spinal surgery using S2AI screws between November 2014 and January 2017 at our institution. Patients with minimum follow-up of two years were included. The following sagittal radiographic parameters were measured: PI, Lumbar lordosis (LL), pelvic tilt (PT), PI-LL, sagittal vertical axis (SVA) at pre-op, post-op and 2-year follow-up. According to the changes in PI at immediate post-operation, patients were classified into two groups; Group A: Changes of PI less than or equal 5° and Group B: Changes of PI greater than 5°. RESULTS: A total of 82 ASD patients (Group A: 32, Group B: 50; mean age of 53.5 ± 12.6 years) with a mean follow-up period of 30.2 ± 9.2 months were included in this study. At immediate post-operation, Group A showed no significant change in PI (45.7° ± 11.4° to 45.3° ± 11.2°, p = 0.749); while Group B had a significant decrease in PI (51.6° ± 14.5° to 40.9° ± 14.0°, p < 0.001). At the last follow-up, 48% patients (24/50) in Group B had a significant increase in PI (32.8° ± 6.4° to 45.8° ± 11.2°, p < 0.001). Intergroup analysis showed that ΔPI, post-op PI, post-op PT and age were significantly different between both groups. In addition, pre-op PI, post-op PI, post-op PT, post-op PI-LL were significantly correlated with ΔPI at last follow-up. Also, logistic regression analysis showed that post-op PI was the associated risk factor (OR = 0.865, p = 0.024) for PI-LL mismatch. CONCLUSION: Our study showed that PI decreased in more than half of ASD patients immediately after spinal surgery using S2AI screws. Approximately 48% of them were able to recover during the 2-year follow-up. Lower pre-op PI, post-op PI and PT were found to be strongly associated with the return of PI. Thus, these current findings indicated that patients with a high PI at pre-operation should not be over-corrected to avoid PI-LL mismatch postoperatively.

Joint control of seasonal timing and plant function types on drought responses of soil respiration in a semiarid grassland.

Globally, droughts are the most widespread climate factor impacting carbon (C) cycling. However, as the second-largest terrestrial C flux, the responses of soil respiration (Rs) to extreme droughts co-regulated by seasonal timing and PFT (plant functional type) are still not well understood. Here, a manipulative extreme-duration drought experiment (consecutive 30 days without rainfall) was designed to address the importance of drought timing (early-, mid-, or late growing season) for Rs and its components (heterotrophic respiration (Rh) and autotrophic respiration (Ra)) under three PFT treatments (two graminoids, two shrubs, and their combination). The results suggested that regardless of PFT, the mid-drought had the greatest negative effects while early-drought overall had little effect on Rh and its dominated Rs. However, PFT treatments had significant effects on Rh and Rs in response to the late drought, which was PFT-dependence: reduction in shrubs and combination but not in graminoids. Path analysis suggested that the decrease in Rs and Rh under droughts was through low soil water content induced reduction in MBC and GPP. These findings demonstrate that responses of Rs to droughts depend on seasonal timing and communities. Future droughts with different seasonal timing and induced shifts in plant structure would bring large uncertainty in predicting C dynamics under climate changes.