Color Standardization and Stain Intensity Calibration for Whole Slide Image-Based Immunohistochemistry Assessment.

Automated quantification of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) using whole slide imaging (WSI) is expected to eliminate subjectivity in visual assessment. However, the color intensity in WSI varies depending on the staining process and scanner device. Such variations affect the image analysis results. This paper presents methods to diminish the influence of color variation produced in the staining process using a calibrator slide consisting of peptide-coated microbeads. The calibrator slide is stained along with tissue sample slides, and the 3,3'-diaminobenzidine (DAB) color intensities of the microbeads are used for calibrating the color variation of the sample slides. An off-the-shelf image analysis tool is employed for the automated assessment, in which cells are classified by the thresholds for the membrane staining. We have adopted two methods for calibrating the color variation based on the DAB color intensities obtained from the calibrator slide: (1) thresholds for classifying the DAB membranous intensity are adjusted, and (2) the color intensity of WSI is corrected. In the experiment, the calibrator slides and tissue of breast cancer slides were stained together on different days and used to test our protocol. With the proposed protocol, the discordance in the HER2 evaluation was reduced to one slide out of 120 slides.

Posterolateral full-endoscopic debridement and irrigation is effective in treating thoraco-lumbar pyogenic spondylodiscitis, except in cases with large abscess cavities.

PURPOSE: To determine the efficacy and poor prognostic factors of posterolateral full-endoscopic debridement and irrigation (PEDI) surgery for thoraco-lumbar pyogenic spondylodiscitis. METHODS: We included 64 patients (46 men, 18 women; average age: 63.7 years) with thoracic/lumbar pyogenic spondylodiscitis who had undergone PEDI treatment and were followed up for more than 2 years. Clinical outcomes after PEDI surgery were retrospectively investigated to analyze the incidence and risk factors for prolonged and recurrent infection. RESULTS: Of 64 patients, 53 (82.8%) were cured of infection after PEDI surgery, and nine (17.2%) had prolonged or recurrent infection. Multivariate analysis demonstrated that significant risk factors for poor prognosis included a large intervertebral abscess cavity (P = 0.02) and multilevel intervertebral infections (P < 0.05). CONCLUSION: PEDI treatment is an effective, minimally invasive procedure for pyogenic spondylodiscitis. However, a large intervertebral abscess space could cause instability at the infected spinal column, leading to prolonged or recurrent infection after PEDI. In cases with a large abscess cavity with or without vertebral bone destruction, endoscopic drainage alone may have a poor prognosis, and spinal fixation surgery could be considered.

Evaluation of Surgical Indications for Full Endoscopic Discectomy at Lumbosacral Disc Levels Using Three-Dimensional Magnetic Resonance/Computed Tomography Fusion Images Created with Artificial Intelligence.

Background and Objectives: Although full endoscopic lumbar discectomy with the transforaminal approach (FED-TF) is a minimally invasive spinal surgery for lumbar disc herniation, the lumbosacral levels present anatomical challenges when performing FED-TF surgery due to the presence of the iliac bone. Materials and Methods: In this study, we simulated whether FED-TF surgery could be safely performed on a total of 52 consecutive cases with L5-S1 or L5-L6 disc herniation using fused three-dimensional (3D) images of the lumbar nerve root on magnetic resonance imaging (MRI) created with artificial intelligence and of the lumbosacral spine and iliac on computed tomography (CT) images. Results: Thirteen of the fifty-two cases were deemed operable according to simulated FED-TF surgery without foraminoplasty using the 3D MRI/CT fusion images. All 13 cases underwent FED-TF surgery without neurological complications, and their clinical symptoms significantly improved. Conclusions: Three-dimensional simulation may allow for the assessment from multiple angles of the endoscope entry and path, as well as the insertion angle. FED-TF surgery simulation using 3D MRI/CT fusion images could be useful in determining the indications for full endoscopic surgery for lumbosacral disc herniation.

Three-Dimensional Vessel Segmentation in Whole-Tissue and Whole-Block Imaging Using a Deep Neural Network: Proof-of-Concept Study.

In the field of pathology, micro-computed tomography (micro-CT) has become an attractive imaging modality because it enables full analysis of the three-dimensional characteristics of a tissue sample or organ in a noninvasive manner. However, because of the complexity of the three-dimensional information, understanding would be improved by development of analytical methods and software such as those implemented for clinical CT. As the accurate identification of tissue components is critical for this purpose, we have developed a deep neural network (DNN) to analyze whole-tissue images (WTIs) and whole-block images (WBIs) of neoplastic cancer tissue using micro-CT. The aim of this study was to segment vessels from WTIs and WBIs in a volumetric segmentation method using DNN. To accelerate the segmentation process while retaining accuracy, a convolutional block in DNN was improved by introducing a residual inception block. Three colorectal tissue samples were collected and one WTI and 70 WBIs were acquired by a micro-CT scanner. The implemented segmentation method was then tested on the WTI and WBIs. As a proof-of-concept study, our method successfully segmented the vessels on all WTI and WBIs of the colorectal tissue sample. In addition, despite the large size of the images for analysis, all segmentation processes were completed in 10 minutes.

Different symptomatic improvement pattern revealed by factor analysis between placebo response and response to Esketamine in treatment resistant depression.

AIMS: The aim of this study is to determine whether there is difference in the change in each symptom of depression and in symptomatic improvement pattern between placebo and antidepressant responses. METHODS: Using data from a randomized, double-blind (DB), placebo-controlled trial of esketamine (ESK) in patients with treatment-resistant depression (TRD), we conducted exploratory analyses. To determine differences in the change in each depressive symptom on the MADRS subscale between placebo and antidepressant responses, a two-way factorial analysis was conducted using the amount of change on Day 2 and 28 of treatment. In addition, exploratory and confirmatory factor analyses were conducted on the MADRS subtotal variables on Day 2 and 28 of treatment to determine symptomatic improvement pattern between placebo response and antidepressant responses. RESULTS: We found that as well as MADRS total score, each subscale of MADRS score did not significantly differ between esketamine and placebo at Day 2 and 28. On the other hand, factor analysis revealed that the factor structure of the response was different between esketamine and placebo at the 2nd day. There was no difference in the factor structure between esketamine and placebo in response on Day 28 of treatment. CONCLUSION: Factor analysis revealed different patterns of symptom improvement in the early phase of the intervention between esketamine and placebo. This finding suggests that a data driven approach may provide detailed efficacy information in clinical trials for antidepressants. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02918318. Registered: 28 September 2016.

Acquisition and Analysis of Microcirculation Image in Septic Model Rats.

Background: Microcirculation is a vital sign that supplies oxygen and nutrients to maintain normal life activities. Sepsis typically influences the operation of microcirculation, which is recovered by the administration of medicine injection. Objective: Sepsis-induced variation and recovery of microcirculation are quantitatively detected using microcirculation images acquired by a non-contact imaging setup, which might assist the clinical diagnosis and therapy of sepsis. Methods: In this study, a non-contact imaging setup was first used to record images of microcirculation on the back of model rats. Specifically, the model rats were divided into three groups: (i) the sham group as a control group; (ii) the cecum ligation and puncture (CLP) group with sepsis; and (iii) the CLP+thrombomodulin (TM) group with sepsis and the application of TM alfa therapy. Furthermore, considering the sparsity of red blood cells (RBCs), the blood velocity is estimated by robust principal component analysis (RPCA) and U-net, and the blood vessel diameter is estimated by the contrast difference between the blood vessel and tissue. Results and Effectiveness: In the experiments, the continuous degradation of the estimated blood velocity and blood vessel diameter in the CLP group and the recovery after degradation of those in the CLP+TM group were quantitatively observed. The variation tendencies of the estimated blood velocity and blood vessel diameter in each group suggested the effects of sepsis and its corresponding therapy.

Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review.

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/ß-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.

Stage-specific meniscal features predict progression of osteoarthritis of the knee: a retrospective cohort study using data from the osteoarthritis initiative.

BACKGROUND: In the progression of osteoarthritis (OA) of the knee, a correlation between meniscal posterior segment injuries and medial meniscal extrusion has been reported, but there have been few reports on the relationship with the meniscal shape. The purpose of this study was to clarify the features of the meniscal shape involved in the progression of knee OA. METHODS: Data were obtained from the Osteoarthritis Initiative (OAI) database. We defined two sets of subjects. One set included 455 knees of subjects whose OA grade on the Kellgren Lawrence (KL) scale progressed in 24 months from baseline and the other set consisted of 455 knees with no progression. The OA progressed subjects were divided to three groups: the "OA change group", KL0 and KL1 knees that progressed to KL2 and KL3; the "mild change group", KL2 knees that progressed to KL3; and the "severe change group", KL2 and KL3 knees that progressed to KL4. The no progression set was divided into three groups whose OA grade remained unchanged. We used magnetic resonance imaging data and manually measured seven items (longitudinal diameter [LD], anterior wedge thickness, anterior wedge width, posterior wedge width, posterior wedge thickness, anterior wedge angle, posterior wedge angle) from the sagittal slice and the extrusion from the coronal slice. These measurements were compared between knees with and without OA progression. RESULTS: In the "OA change group" and "mild change group", the anterior and posterior wedge widths and the extrusion were significantly larger, but the anterior and the posterior wedge angles were significantly smaller. In the "severe change group," the LD and the extrusion were significantly larger. In each group, there was no uniform tendency for the correlation coefficient of the parameters evaluated. CONCLUSIONS: Our findings suggested (1) a larger meniscal LD at the baseline predicted progression of knee OA after 24 months and (2) a larger meniscal width and smaller meniscal angle predicted progression of knee OA after 24 months.

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis.

BACKGROUND: Comparative evidence for efficacy and safety of second-generation cholinesterase inhibitors (ChEIs) is still sparse. OBJECTIVES: The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: We conducted a systematic review for published articles and included randomised, double-blind, placebo-controlled trials and head-to-head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta-analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions. RESULTS: Among the 21 trials included, network meta-analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS-Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety. CONCLUSIONS: Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD.

Effects of Multiple Intra-articular Injections of 0.5% Bupivacaine on Normal and Osteoarthritic Joints in Rats.

PURPOSE: To determine the in vivo effects of multiple local anesthetic injections of 0.5% bupivacaine on normal and osteoarthritic articular cartilage. METHODS: Rats with normal knee joints received an intra-articular injection of 0.9% saline solution or 0.5% bupivacaine in their right knees joint once a week for 5 consecutive weeks, starting 4 weeks after the beginning of the experiment. Rats were humanely killed at 8, 16, and 24 weeks. In a parallel experiment, rats underwent anterior cruciate ligament transection to induce osteoarthritic changes. These rats were subjected to the same protocol as those with normal knee joints, starting 4 weeks after the procedure. Static weight-bearing tests were performed on both hind limbs to evaluate changes in weight-bearing ability throughout the experiments. Rats were humanely killed at 8 and 16 weeks. Cell viability was assessed with confocal microscopy, using samples from the distal femur. Histologic assessment of osteoarthritis was performed using samples from the tibial plateau based on the Osteoarthritis Research Society International (OARSI) cartilage histopathology assessment system (i.e., OARSI score). RESULTS: Static weight-bearing tests showed no significant changes after intra-articular injection of saline solution or bupivacaine, and bupivacaine injection did not increase weight bearing compared with saline solution injection, regardless of whether there were osteoarthritic changes. There were also no significant differences in cell viability, cell density, or OARSI scores between the saline solution and bupivacaine groups at each time point, regardless of whether osteoarthritic changes were induced. CONCLUSIONS: This study suggested that single or intermittent intra-articular bupivacaine injections might not have deleterious effects on either osteoarthritic or normal joints. CLINICAL RELEVANCE: There is no strong evidence that intra-articular bupivacaine injection induces degenerative changes in articular cartilage. Therefore, these results may apply to normal and osteoarthritic joints.

Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study.

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.

Reduced dopamine transporter availability in drug-naive adult attention-deficit/hyperactivity disorder.

Aim: This study aimed to clarify the abnormalities in dopamine transporter (DAT) availability in drug-naive adult patients with attention-deficit/hyperactivity disorder (ADHD) and the relationship between ADHD symptoms and abnormalities in DAT availability. Methods: Single-photon emission tomography (SPECT) was performed using iodine-123-ß-carbomethoxy-3ß-(4-iodophenyltropane) (I-123 ß CIT) as a tracer to measure in vivo DAT availability in 20 drug-naive patients with ADHD [mean age ± standard deviation (SD)]: 25 ± 3.44 years; male:female = 11:9] and 20 age- and sex-matched healthy controls (HCs) (mean age ± SD: 23.9 ± 2.27 years). Comparisons of DAT availability between HCs and adult patients with ADHD and the association between symptom severity and DAT availability within the ADHD group were analyzed using Statistical Parametric Mapping 12. Results: Drug-naive adults with ADHD showed significantly reduced DAT availability in the bilateral nucleus accumbens compared with HCs. Correlation analyses revealed a negative correlation between the severity of inattentive symptoms in adult patients with ADHD and DAT availability in the bilateral heads of the caudate nucleus, indicating the association between severe inattentive symptoms and lower DAT availability in the caudate nucleus. Conclusion: In drug-naive adult patients with ADHD, DAT availability was reduced in the nucleus accumbens, an important part of the reward system. This finding indicates the importance of the DAT in the reward system in the pathogenesis of ADHD. Inattentiveness was associated with DAT availability in the caudate nucleus, suggesting involvement of the cortico-striato-thalamo-cortical circuit.

Deep learning-based detection of lumbar spinal canal stenosis using convolutional neural networks.

BACKGROUND CONTEXT: Lumbar spinal canal stenosis (LSCS) is the most common spinal degenerative disorder in elderly people and usually first seen by primary care physicians or orthopedic surgeons who are not spine surgery specialists. Magnetic resonance imaging (MRI) is useful in the diagnosis of LSCS, but the equipment is often not available or difficult to read. LSCS patients with progressive neurologic deficits have difficulty with recovery if surgical treatment is delayed. So, early diagnosis and determination of appropriate surgical indications are crucial in the treatment of LSCS. Convolutional neural networks (CNNs), a type of deep learning, offers significant advantages for image recognition and classification, and work well with radiographs, which can be easily taken at any facility. PURPOSE: Our purpose was to develop an algorithm to diagnose the presence or absence of LSCS requiring surgery from plain radiographs using CNNs. STUDY DESIGN: Retrospective analysis of consecutive, nonrandomized series of patients at a single institution. PATIENT SAMPLE: Data of 150 patients who underwent surgery for LSCS, including degenerative spondylolisthesis, at a single institution from January 2022 to August 2022, were collected. Additionally, 25 patients who underwent surgery at 2 other hospitals were included for extra external validation. OUTCOME MEASURES: In annotation 1, the area under the curve (AUC) computed from the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. In annotation 2, correlation coefficients were used. METHODS: Four intervertebral levels from L1/2 to L4/5 were extracted as region of interest from lateral plain lumbar spine radiographs totaling 600 images were obtained. Based on the date of surgery, 500 images derived from the first 125 cases were used for internal validation, and 100 images from the subsequent 25 cases used for external validation. Additionally, 100 images from other hospitals were used for extra external validation. In annotation 1, binary classification of operative and nonoperative levels was used, and in annotation 2, the spinal canal area measured on axial MRI was labeled as the output layer. For internal validation, the 500 images were divided into each 5 dataset on per-patient basis and 5-fold cross-validation was performed. Five trained models were registered in the external validation prediction performance. Grad-CAM was used to visualize area with the high features extracted by CNNs. RESULTS: In internal validation, the AUC and accuracy for annotation 1 ranged between 0.85-0.89 and 79-83%, respectively, and the correlation coefficients for annotation 2 ranged between 0.53 and 0.64 (all p<.01). In external validation, the AUC and accuracy for annotation 1 were 0.90 and 82%, respectively, and the correlation coefficient for annotation 2 was 0.69, using 5 trained CNN models. In the extra external validation, the AUC and accuracy for annotation 1 were 0.89 and 84%, respectively, and the correlation coefficient for annotation 2 was 0.56. Grad-CAM showed high feature density in the intervertebral joints and posterior intervertebral discs. CONCLUSIONS: This technology automatically detects LSCS from plain lumbar spine radiographs, making it possible for medical facilities without MRI or nonspecialists to diagnose LSCS, suggesting the possibility of eliminating delays in the diagnosis and treatment of LSCS that require early treatment.

A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.

Standardizing HER2 immunohistochemistry assessment: calibration of color and intensity variation in whole slide imaging caused by staining and scanning.

In the evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) - one of the standard biomarkers for breast cancer- visual assessment is laborious and subjective. Image analysis using whole slide image (WSI) could produce more consistent results; however, color variability in WSIs due to the choice of stain and scanning processes may impact image analysis. We therefore developed a calibration protocol to diminish the staining and scanning variations of WSI using two calibrator slides. The IHC calibrator slide (IHC-CS) contains peptide-coated microbeads with different concentrations. The color distribution obtained from the WSI of stained IHC-CS reflects the staining process and scanner characteristics. A color chart slide (CCS) is also useful for calibrating the color variation due to the scanner. The results of the automated HER2 assessment were compared to confirm the effectiveness of two calibration slides. The IHC-CS and HER2 breast cancer cases were stained on different days. All stained slides and CCS were digitized by two different WSI scanners. Results revealed 100% concordance between automated evaluation and the pathologist's assessment with both the scanner and staining calibration. The proposed method may enable consistent evaluation of HER2.

Influence of Lateral Translation of Lowest Instrumented Vertebra on L4 Tilt and Coronal Balance for Thoracolumbar and Lumbar Curves in Adolescent Idiopathic Scoliosis.

This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.

Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc.

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in the spine. Vertebrae in ank mice exhibit elevated cortical bone mass and increased tissue non-specific alkaline phosphatase-positive endplate chondrocytes with decreased subchondral endplate porosity. The acellular dystrophic mineral inclusions in the annulus fibrosus were localized adjacent to apoptotic cells and cells that acquired osteoblast-like phenotype. Fourier transform infrared spectral imaging showed that the apatite mineral in the outer annulus fibrosus had similar chemical composition to that of vertebral bone. Transcriptomic analysis of annulus fibrosus and nucleus pulposus tissues showed changes in several biological themes with a prominent dysregulation of BMAL1/CLOCK circadian regulation. The present study provides new insights into the role of ANK in the disc tissue compartments and highlights the importance of local inorganic pyrophosphate metabolism in inhibiting the mineralization of this important connective tissue.

The Use of Deep Learning-Based Computer Diagnostic Algorithm for Detection of Lymph Node Metastases of Gastric Adenocarcinoma.

Objectives. The diversifying modalities of treatment for gastric cancer raise urgent demands for the rapid and precise diagnosis of metastases in regional lymph nodes, thereby significantly impact the workload of pathologists. Meanwhile, the recent advent of whole-slide scanners and deep-learning techniques have enabled the computer-assisted analysis of histopathological images, which could help to alleviate this impact. Thus, we developed a deep learning-based diagnostic algorithm to detect lymph node metastases of gastric adenocarcinoma and evaluated its performance. Methods. We randomly selected 20 patients with gastric adenocarcinoma who underwent surgery as definitive treatment and were found to be node metastasis-positive. HEMATOXYLIN-eosin (HE) stained glass slides, including a total of 51 metastasis-positive nodes, were retrieved from the specimens of these cases. Other slides with 776 metastasis-negative nodes were also retrieved from other twenty cases with the same disease that were diagnosed as metastasis-negative by the final pathological examinations. All glass slides were digitized using a whole-slide scanner. A deep-learning algorithm to detect metastases was developed using the data in which metastasis-positive parts of the images were annotated by a well-trained pathologist, and its performance in detecting metastases was evaluated. Results. Cross-validation analysis indicated an area of 0.9994 under the receiver operating characteristic curve. Free-response receiver operating characteristic curve (FROC) analysis indicated a sensitivity of 1.00 with three false positives. Further evaluation using an independent dataset also showed similar level of accuracies. Conclusion. This deep learning-based diagnosis-aid system is a promising tool that can assist pathologists involved in gastric cancer care and reduce their workload.

Disrupted structural connectivity and less efficient network system in patients with the treatment-naive adult attention-deficit/hyperactivity disorder.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder whose primary symptoms are hyperactivity, impulsivity, and inattention. Historically, ADHD was recognized as a disease of childhood and adolescence. However, many patients are known to have persistent symptoms into adulthood. Many researchers consider the neuropathology of ADHD to be based on abnormalities in multiple parallel and intersecting pathways rather than a single anatomical area, but such alterations remain to be clarified. Methods: Using diffusion tensor imaging, we investigated differences in the global network metrics estimated by graph theory and the degree of connectivity between adjacent voxels within a white matter (WM) fascicle defined by the density of the diffusing spins (connectometry) between 19 drug-naive Japanese patients with adult ADHD and 19 matched healthy controls (HCs). In adult patients with ADHD, we examined the relationships between the symptomatology of ADHD and global network metrics and WM abnormalities. Results: Compared with HCs, adult patients with ADHD showed a reduced rich-club coefficient and decreased connectivity in widely distributed WMs such as the corpus callosum, the forceps, and the cingulum bundle. Correlational analyses demonstrated that the general severity of ADHD symptoms was associated with several global network metrics, such as lower global efficiency, clustering coefficient, small worldness, and longer characteristic path length. The connectometry revealed that the severity of hyperactive/impulsive symptoms was associated with overconnectivity in the corticostriatal, corticospinal, and corticopontine tracts, the inferior fronto-occipital fasciculus, and the extreme capsule but dysconnectivity in the cerebellum. The severity of inattentive symptoms was associated with dysconnectivity in the intracerebellar circuit and some other fibers. Conclusion: The results of the present study indicated that patients with treatment-naive adult ADHD showed disrupted structural connectivity, which contributes to less efficient information transfer in the ADHD brain and pathophysiology of ADHD. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000025183, Registered: 5 January 2017.

Computer-aided diagnosis for screening of lower extremity lymphedema in pelvic computed tomography images using deep learning.

Lower extremity lymphedema (LEL) is a common complication after gynecological cancer treatment, which significantly reduces the quality of life. While early diagnosis and intervention can prevent severe complications, there is currently no consensus on the optimal screening strategy for postoperative LEL. In this study, we developed a computer-aided diagnosis (CAD) software for LEL screening in pelvic computed tomography (CT) images using deep learning. A total of 431 pelvic CT scans from 154 gynecological cancer patients were used for this study. We employed ResNet-18, ResNet-34, and ResNet-50 models as the convolutional neural network (CNN) architecture. The input image for the CNN model used a single CT image at the greater trochanter level. Fat-enhanced images were created and used as input to improve classification performance. Receiver operating characteristic analysis was used to evaluate our method. The ResNet-34 model with fat-enhanced images achieved the highest area under the curve of 0.967 and an accuracy of 92.9%. Our CAD software enables LEL diagnosis from a single CT image, demonstrating the feasibility of LEL screening only on CT images after gynecologic cancer treatment. To increase the usefulness of our CAD software, we plan to validate it using external datasets.