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The Ki-67 labeling index is essential for predicting the prognosis of breast cancer and for diagnosing neuroendocrine and gastrointestinal stromal tumors. However, current manual counting and digital image analysis (DIA)-based methods are limited in terms of accurate estimation. This study aimed to assess and compare the capabilities of different DIA systems for Ki-67 counting using the conventional manual counting method. A total of 239 tissue microarray cores from patients with stomach cancer were immunohistochemically stained for Ki-67 and digitally scanned. For the analysis, we employed three different annotation methods: whole TMA core, box selection of the epithelium, and hand-free selection of the epithelium. We used DIA system of 3DHistech, Roche, aetherAI, and manual counting by the pathologists. The annotation methods showed different Ki-67 positivity but were lower than the pathologist manual counting. The results demonstrate that the Roche system is the preferred method for analyzing the entire TMA, whereas aetherAI outperforms the box selection method. Furthermore, 3DHistech is the most accurate method for hands-free selection of the epithelium. The manual counting results showed good agreement among pathologists, with an average intraclass correlation coefficient of 0.93. These results emphasize the importance of carefully selecting annotation methods to determine Ki-67 positivity. To determine the most suitable method for individual laboratories, multiple approaches should be assessed before implementing a DIA system in routine practice., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing. Nanomesh elastic neuroelectronics are validated using single-unit recording from the small and curvilinear epidural surface of mouse dorsal root ganglia (DRG) with device self-conformed and superior recording quality compared to plastic control devices requiring manual pressing is demonstrated. Electrode scaling studies from in vivo epidural recording further revealed the need for cellular resolution for high-fidelity recording of single-unit activities and compound action potentials. In addition to creating a minimally invasive device to effectively interface with DRG sensory afferents at a single-cell resolution, this study establishes nanomeshing as a practical pathway to leverage traditional electrode materials for a new class of elastic neuroelectronics., (© 2024 Wiley‐VCH GmbH.)

Background: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well., Materials and Methods: We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray., Results: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers ( P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses ( P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers., Conclusions: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 60-year-old man diagnosed with gastric adenocarcinoma underwent FDG PET/CT. After completing 9 cycles of combination chemotherapy with nivolumab and FOLFOX, he had multiple new nodular uptakes in the bilateral cervical chains and mediastinum. The pathology of the right neck node confirmed reactive lymph node hyperplasia without evidence of malignancy, suggesting pseudoprogression after immunotherapy. It is worthwhile to report these PET image patterns, as they could significantly influence clinical decision-making., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC., Methods: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically., Results: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2., Conclusion: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background/aim: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells., Methods: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT., Results: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm 2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05)., Conclusions: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiun Suk Chae reports financial support was provided by National Research Foundation of Korea. Hiun Suk Chae reports a relationship with National Research Foundation of Korea that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we investigated whether transient receptor melastatin 7 (TRPM7), known as a non-selective cation channel, inhibits neuropathic pain after spinal cord injury (SCI) and how TRPM7 regulates neuropathic pain. Neuropathic pain was developed 4 weeks after moderate contusive SCI and TRPM7 was markedly upregulated in astrocytes in the lamina I and II of L4-L5 dorsal horn. In addition, both mechanical allodynia and thermal hyperalgesia were significantly alleviated by a TRPM7 inhibitor, carvacrol. In particular, carvacrol treatment inhibited mechanistic target of rapamycin (mTOR) signaling, which was activated in astrocytes. When rats were treated with rapamycin, an inhibitor of mTOR signaling, neuropathic pain was significantly inhibited. Furthermore, blocking TRPM7 and mTOR signaling by carvacrol and rapamycin inhibited astrocyte activation in lamina I and II of dorsal spinal cord and reduced the level of p-JNK and p-c-Jun, which are known to be activated in astrocytes. Finally, inhibiting TRPM7/mTOR signaling also downregulated the production of pain-related factors such as tumor necrosis factor-α, interleukin-6, interleukin-1β, chemokine (C-C motif) ligand (CCL) 2, CCL-3, CCL-4, CCL-20, chemokine C-X-C motif ligand 1, and matrix metalloproteinase 9 which are known to be involved in the induction and/or maintenance of neuropathic pain after SCI. These results suggest an important role of TRPM7-mediated mTOR signaling in astrocyte activation and thereby induction and/or maintenance of neuropathic pain after SCI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images (WSIs) of thyroid fine-needle aspiration cytology (FNA), incorporating z-stacking, from institutions across the nation to develop an AI model. Methods: We conducted a multicenter retrospective diagnostic accuracy study using thyroid FNA dataset from the Open AI Dataset Project that consists of digitalized images samples collected from 3 university hospitals and 215 Korean institutions through extensive quality check during the case selection, scanning, labeling, and reviewing process. Multiple z-layer images were captured using three different scanners and image patches were extracted from WSIs and resized after focus fusion and color normalization. We pretested six AI models, determining Inception ResNet v2 as the best model using a subset of dataset, and subsequently tested the final model with total datasets. Additionally, we compared the performance of AI and cytopathologists using randomly selected 1031 image patches and reevaluated the cytopathologists' performance after reference to AI results. Results: A total of 10,332 image patches from 306 thyroid FNAs, comprising 78 malignant (papillary thyroid carcinoma) and 228 benign from 86 institutions were used for the AI training. Inception ResNet v2 achieved highest accuracy of 99.7%, 97.7%, and 94.9% for training, validation, and test dataset, respectively (sensitivity 99.9%, 99.6%, and 100% and specificity 99.6%, 96.4%, and 90.4% for training, validation, and test dataset, respectively). In the comparison between AI and human, AI model showed higher accuracy and specificity than the average expert cytopathologists beyond the two-standard deviation (accuracy 99.71% [95% confidence interval (CI), 99.38-100.00%] vs. 88.91% [95% CI, 86.99-90.83%], sensitivity 99.81% [95% CI, 99.54-100.00%] vs. 87.26% [95% CI, 85.22-89.30%], and specificity 99.61% [95% CI, 99.23-99.99%] vs. 90.58% [95% CI, 88.80-92.36%]). Moreover, after referring to the AI results, the performance of all the experts (accuracy 96%, 95%, and 96%, respectively) and the diagnostic agreement (from 0.64 to 0.84) increased. Conclusions: These results suggest that the application of AI technology to thyroid FNA cytology may improve the diagnostic accuracy as well as intra- and inter-observer variability among pathologists. Further confirmatory research is needed.

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma.

Background: The purpose of this study was to evaluate the clinical and radiological outcomes of high-flexion total knee arthroplasty (TKA) using Vega Knee System (B. Braun, Aesculap) at a long-term follow-up and to analyze the implant survivorship., Methods: We enrolled 165 patients (232 knees) with a minimum 7-year follow-up after TKA (VEGA Knee System). For clinical assessment, range of motion (ROM), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used. For radiologic assessment, hip-knee-ankle angle, component position, and the existence of radiolucent lines and loosening were used. Survival analysis was conducted using the Kaplan-Meier method., Results: The mean follow-up period was 9.8 years. The mean ROM increased from 124.4° to 131.4° at the final follow-up. The WOMAC score decreased from 38.5 to 17.4 at the final follow-up ( p < 0.001). All 5 subscales of the KOOS improved at the final follow-up (all subscales, p < 0.001). Revision TKA was performed in 10 cases (4.3%), which included 9 cases of aseptic loosing and 1 case of periprostatic joint infection. Of the 9 aseptic loosening cases (3.9%), 8 cases (3.4%) were loosening of the femoral component and 1 case (0.4%) was loosening of the tibial component. When revision for any reason was considered an endpoint, the 10-year survivorship was 96.2% (95% confidence interval [CI], 93.9%-98.5%). On the other hand, when revision for aseptic loosening was considered the endpoint, the 10-year survivorship was 96.6% (95% CI, 94.4%-98.8%)., Conclusions: The Vega Knee System provided good clinical results in the long-term follow-up period. Although the VEGA Knee System showed acceptable implant survivorship, loosening of the femoral component occurred in about 3.4% of the patients. For more accurate evaluation of the survivorship of high-flexion design TKA with a short posterior flange, it is necessary to conduct more long-term follow-up studies targeting diverse races, especially Asians who frequently perform high-flexion activities., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to diagnose based on biopsy findings, and ascitic aspiration cytology has a low sensitivity and specificity and a high inter-observer variability. The aim of the present study was to apply artificial intelligence (AI) to classify benign and malignant cells in ascites cytology patch images of metastatic CRC using a deep convolutional neural network. Datasets were collected from The OPEN AI Dataset Project, a nationwide cytology dataset for AI research. The numbers of patch images used for training, validation, and testing were 56,560, 7068, and 6534, respectively. We evaluated 1041 patch images of benign and metastatic CRC in the ascitic fluid to compare the performance of pathologists and an AI algorithm, and to examine whether the diagnostic accuracy of pathologists improved with the assistance of AI. This AI method showed an accuracy, a sensitivity, and a specificity of 93.74%, 87.76%, and 99.75%, respectively, for the differential diagnosis of malignant and benign ascites. The diagnostic accuracy and sensitivity of the pathologist with the assistance of the proposed AI method increased from 86.8% to 90.5% and from 73.3% to 79.3%, respectively. The proposed deep learning method may assist pathologists with different levels of experience in diagnosing metastatic CRC cells of ascites.

After spinal cord injury (SCI), secondary injuries including blood cells infiltration followed by the production of inflammatory mediators are led by blood-spinal cord barrier (BSCB) breakdown. Therefore, preventing BSCB damage could alleviate the secondary injury progresses after SCI. Recently, we reported that transient receptor potential melastatin 7 channel (TRPM7) expression is increased in vascular endothelial cells after injury and thereby mediates BSCB disruption. However, the mechanism by which TRPM7 regulates BSCB disruption has not been examined yet. In current research, we show that TRPM7 mediates BSCB disruption via mammalian target of rapamycin (mTOR) pathway after SCI in rats. After contusion injury at T9 level of spinal cord, mTOR pathway was activated in the endothelial cells of blood vessels and TRPM7 was involved in the activation of mTOR pathway. BSCB disruption, MMP-2/9 activation, and blood cell infiltration after injury were alleviated by rapamycin, a mTOR signaling inhibitor. Rapamycin also conserved the level of tight junction proteins, which were decreased after SCI. Furthermore, mTOR pathway regulated the expression and activation of histone H3K27 demethylase JMJD3, known as a key epigenetic regulator mediating BSCB damage after SCI. In addition, rapamycin inhibited JMJD3 expression, the loss of tight junction molecules, and MMP-2/9 expression in bEnd.3, a brain endothelial cell line, after oxygen-glucose deprivation/reoxygenation. Thus, our results suggest that TRPM7 contributes to the BSCB disruption by regulating JMJD3 expression through the mTOR pathway after SCI., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Many reports on the development of myocarditis following coronavirus disease 2019 (COVID-19) vaccination (PCVM) have emerged. However, only a few case studies have investigated endomyocardial biopsy (EMB) results. This study describes the clinicopathologic features of PCVM. We surveyed all hospitalized patients in a single university hospital in Korea and identified six cases of PCVM. All six patients underwent EMB, five of whom were men aged 15-85 years. All patients developed cardiac dysfunction. Among these patients, two had mild disease without sequelae, whereas the other four had dilated cardiomyopathy with depressed cardiac function. All six cases demonstrated lymphohistiocytic myocarditis. Two of our cases fulfilled the criterion of CD3+ T lymphocytes > 7 cells/mm 2 (Case nos. 3 and 6), while the remaining four cases did not fulfill the Dallas criteria. In conclusion, most PCVM cases showed mild degree inflammation histopathologically, and some cases could not fulfill the Dallas criteria and were classified as borderline myocarditis.

After spinal cord injury (SCI), the control of activated glial cells such as microglia and astrocytes has emerged as a promising strategy for neuropathic pain management. However, signaling mechanism involved in glial activation in the process of neuropathic pain development and maintenance after SCI is not well elucidated. In this study, we investigated the potential role and mechanism of the JAK2/STAT3 pathway associated with glial cell activation in chronic neuropathic pain development and maintenance after SCI. One month after contusive SCI, the activation of JAK2/STAT3 pathway was markedly upregulated in both microglia and astrocyte in nociceptive processing regions of the lumbar spinal cord. In addition, both mechanical allodynia and thermal hyperalgesia was significantly inhibited by a JAK2 inhibitor, AG490. In particular, AG490 treatment inhibited both microglial and astrocyte activation in the lumbar (L) 4-5 dorsal horn and significantly decreased levels of p-p38MAPK, p-ERK and p-JNK, which are known to be activated in microglia (p-p38MAPK and p-ERK) and astrocyte (p-JNK). Experiments using primary cell cultures also revealed that the JAK2/STAT3 pathway promoted microglia and astrocyte activation after lipopolysaccharide stimulation. Furthermore, JAK2/STAT3 signaling and pain behaviors were significantly attenuated when the rats were treated with anti-IL-6 antibody. Finally, minocycline, a tetracycline antibiotic, inhibited IL-6/JAK2/STAT3 signaling pathway in activated glial cells and restored nociceptive thresholds and the hyperresponsiveness of dorsal neurons. These results suggest an important role of the IL-6/JAK2/STAT3 pathway in the activation of microglia and astrocytes and in the maintenance of chronic below-level pain after SCI., Competing Interests: Declaration of Competing Interest No., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Design: Histologic analysis of the ligamentum flavum (LF) in the lumbar spine., Objective: The objective of this study is to investigate the levels of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the LF tissue of patients with lumbar spinal stenosis (LSS)., Summary of Background Data: The hypertrophy of the LF is the primary cause of the progression of LSS. Recently, Wnt signaling has been proposed as one of the molecular processes contributing to LF hypertrophy. GSK-3β and β-catenin are recognized to play a crucial part in the control of this signaling pathway., Materials and Methods: From May 2020 to July 2022, LF from 51 LSS patients (LSS group) and 18 lumbar disc herniation patients (control group) were prospectively collected during surgery. Histologic analysis was investigated to confirm the progression of LF fibrosis. The levels of α-smooth muscle actin, phosphorylation of GSK-3β (p-GSK-3β; inactive form), and β-catenin were analyzed in LF with Western blot analysis to reveal the GSK-3β/β-catenin signaling pathway. Continuous variables are expressed as mean±SD and compared using the student t test. Categorical variables are compared using the χ 2 test or Fisher exact test, as appropriate. To determine the association between p-GSK-3β and LF thickness, the Pearson correlation coefficient was calculated based on the results of Western blot analysis., Results: The LSS group was older and had thicker LF than the controls. The LSS group showed increased collagen fiber and cellularity than the controls. The levels of α-smooth muscle actin, p-GSK-3β, and β-catenin in the LF of the LSS group were significantly higher than that of the control group. There was a strong positive correlation between p-GSK-3β (Ser9) level and LF thickness in LSS patients ( r =0.69, P =0.01)., Conclusion: This research proposes a molecular mechanism for the pathogenesis of LF hypertrophy in LSS. Specifically, GSK-3β/β-catenin signaling appears to be related to LF hypertrophy in LSS and a positive correlation exists between p-GSK-3β level and LF thickness., Level of Evidence: Level 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Distant metastasis of cholangiocarcinoma is most commonly diagnosed in the liver; however, it can also be found in the lungs, distant lymph nodes, bones, and brain. Distant lymph node metastasis outside the abdominal region without concurrent abdominal metastasis is exceedingly rare in extrahepatic cholangiocarcinoma. Herein, we present interesting 18 F-FDG PET/CT images of a 49-year-old male patient with common bile duct cancer. In this case, the patient, who was scheduled for surgery, unexpectedly showed axillary lymph node metastasis on a preoperative 18 F-FDG PET scan, which was subsequently confirmed via histological examination. Although such cases are exceptionally rare, this accurate diagnosis prompted a modification of the treatment plan, leading to a positive therapeutic response.

Metastatic urothelial carcinoma of the renal pelvis (MUCP), a type of metastatic upper tract urothelial carcinoma (MUTUC), is a rare malignancy, and some patients with MUCP present with distant metastasis at the time of diagnosis. MUCP in the gastrointestinal tract is even rarer. Herein, we report a 78-year-old man with MUCP that presented as a duodenal ulcer. He complained of anorexia, dizziness, and melena for one month. Endoscopic examination at a local clinic revealed a duodenal hemorrhagic and ulcerative lesion, and the patient was referred. He noted dark-colored stools with increasing frequency, but he denied hematochezia, coffee ground emesis, weight changes, or abdominal pain. Gastroduodenoscopic examination at our hospital demonstrated an ulcerofungating lesion of the second portion of the duodenum. Colonoscopic findings showed no abnormality. Computed tomography showed a 6.7 cm sized mass abutting the inferior vena cava, second portion of the duodenum, lower pole of the right kidney, and right iliopsoas. The mass showed heterogeneous enhancement and internal hemorrhagic necrosis and infiltrated the perinephric soft tissues, the second portion of the duodenum, the right psoas muscle, the right renal vein, and the right adrenal gland. Duodenal biopsy showed moderately differentiated squamous cell carcinoma. Immunohistochemistry (IHC) showed diffuse and strong positivity for CK5/6. Tissue from the liver biopsy showed similar histopathologic features and showed GATA3 positivity on IHC. The imprint cytology smears of the liver tissue showed "cercariform" cell features. We confirmed the diagnosis as MUCP. This case illustrated a rare cause of a secondary duodenal tumor, MUCP.

Angioleiomyoma, a rare variant of leiomyoma, is a benign tumor of mesenchymal origin. Angioleiomyomas of the female urogenital tract are extremely rare, with only six cases of uterine cervical angioleiomyoma previously reported in the literature. In this case study, we report on a 49-year-old female patient who presented with menorrhagia whose initial magnetic resonance imaging (MRI) findings suggested cervical squamous cell carcinoma (SCC). However, following the hysterectomy, histological examination confirmed the lesion to be angioleiomyoma. To the best of our knowledge, there have been no previously reported cases of angioleiomyomas presenting with MRI findings that are suggestive of uterine SCC. Recognizing that angioleiomyomas can mimic uterine malignancies on MRI may prove beneficial for future diagnostic and treatment strategies.

A Pleural effusion cytology is vital for treating metastatic breast cancer; however, concerns have arisen regarding the low accuracy and inter-observer variability in cytologic diagnosis. Although artificial intelligence-based image analysis has shown promise in cytopathology research, its application in diagnosing breast cancer in pleural fluid remains unexplored. To overcome these limitations, we evaluate the diagnostic accuracy of an artificial intelligence-based model using a large collection of cytopathological slides, to detect the malignant pleural effusion cytology associated with breast cancer. This study includes a total of 569 cytological slides of malignant pleural effusion of metastatic breast cancer from various institutions. We extracted 34,221 augmented image patches from whole-slide images and trained and validated a deep convolutional neural network model (DCNN) (Inception-ResNet-V2) with the images. Using this model, we classified 845 randomly selected patches, which were reviewed by three pathologists to compare their accuracy. The DCNN model outperforms the pathologists by demonstrating higher accuracy, sensitivity, and specificity compared to the pathologists (81.1% vs. 68.7%, 95.0% vs. 72.5%, and 98.6% vs. 88.9%, respectively). The pathologists reviewed the discordant cases of DCNN. After re-examination, the average accuracy, sensitivity, and specificity of the pathologists improved to 87.9, 80.2, and 95.7%, respectively. This study shows that DCNN can accurately diagnose malignant pleural effusion cytology in breast cancer and has the potential to support pathologists.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination., (© 2023. The Author(s).)

Purpose: Evaluation of genetic mutations in cancers is important because distinct mutational profiles help determine individualized drug therapy. However, molecular analyses are not routinely performed in all cancers because they are expensive, time-consuming and not universally available. Artificial intelligence (AI) has shown the potential to determine a wide range of genetic mutations on histologic image analysis. Here, we assessed the status of mutation prediction AI models on histologic images by a systematic review., Methods: A literature search using the MEDLINE, Embase and Cochrane databases was conducted in August 2021. The articles were shortlisted by titles and abstracts. After a full-text review, publication trends, study characteristic analysis and comparison of performance metrics were performed., Results: Twenty-four studies were found mostly from developed countries, and their number is increasing. The major targets were gastrointestinal, genitourinary, gynecological, lung and head and neck cancers. Most studies used the Cancer Genome Atlas, with a few using an in-house dataset. The area under the curve of some of the cancer driver gene mutations in particular organs was satisfactory, such as 0.92 of BRAF in thyroid cancers and 0.79 of EGFR in lung cancers, whereas the average of all gene mutations was 0.64, which is still suboptimal., Conclusion: AI has the potential to predict gene mutations on histologic images with appropriate caution. Further validation with larger datasets is still required before AI models can be used in clinical practice to predict gene mutations., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Advanced glycation end-products (AGEs; e.g., glyoxal, methylglyoxal or carboxymethyl-lysine) are heterogenous group of toxic compounds synthesized in the body through both exogenous and endogenous pathways. AGEs are known to covalently modify proteins bringing about loss of functional alteration in the proteins. AGEs also interact with their receptor, receptor for AGE (RAGE) and such interactions influence different biological processes including oxidative stress and apoptosis. Previously, AGE-RAGE axis has long been considered to be the maligning factor for various human diseases including, diabetes, obesity, cardiovascular, aging, etc. Recent developments have revealed the involvement of AGE-RAGE axis in different pathological consequences associated with the onset of neurodegeneration including, disruption of blood brain barrier, neuroinflammation, remodeling of extracellular matrix, dysregulation of polyol pathway and antioxidant enzymes, etc. In the present article, we attempted to describe a new avenue that AGE-RAGE axis culminates to different pathological consequences in brain and therefore, is a central instigating component to several neurodegenerative diseases (NGDs). We also invoke that specific inhibitors of TIR domains of TLR or RAGE receptors are crucial molecules for the therapeutic intervention of NGDs. Clinical perspectives have also been appropriately discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bhattacharya, Alam, Kamal, Seo and Singh.)

(1) Background: Differential diagnosis using immunohistochemistry (IHC) panels is a crucial step in the pathological diagnosis of hematolymphoid neoplasms. In this study, we evaluated the prediction accuracy of the ImmunoGenius software using nationwide data to validate its clinical utility. (2) Methods: We collected pathologically confirmed lymphoid neoplasms and their corresponding IHC results from 25 major university hospitals in Korea between 2015 and 2016. We tested ImmunoGenius using these real IHC panel data and compared the precision hit rate with previously reported diagnoses. (3) Results: We enrolled 3052 cases of lymphoid neoplasms with an average of 8.3 IHC results. The precision hit rate was 84.5% for these cases, whereas it was 95.0% for 984 in-house cases. (4) Discussion: ImmunoGenius showed excellent results in most B-cell lymphomas and generally showed equivalent performance in T-cell lymphomas. The primary reasons for inaccurate precision were atypical IHC profiles of certain cases, lack of disease-specific markers, and overlapping IHC profiles of similar diseases. We verified that the machine-learning algorithm could be applied for diagnosis precision with a generally acceptable hit rate in a nationwide dataset. Clinical and histological features should also be taken into account for the proper use of this system in the decision-making process.

We study whether deep neural network based algorithm can filter out mammography phantom images that will pass or fail. With 543 phantom images generated from a mammography unit, we created VGG16 based phantom shape scoring models (multi-and binary-class classifiers). Using these models we designed filtering algorithms that can filter failed or passed phantom images. 61 phantom images obtained from two different medical institutions were used for external validation. The performances of the scoring models show an F1-score of 0.69 (95% confidence interval (CI) 0.65, 0.72) for multi-class classifiers and an F1-score of 0.93 (95% CI 0.92, 0.95) and area under the receiver operating characteristic curve of 0.97 (95% CI 0.96, 0.98) for binary-class classifiers. A total of 42 of the 61 phantom images (69%) were filtered by the filtering algorithms without further need for assessment from a human observer. This study demonstrated the potential to reduce the human workload from mammographic phantom interpretation using the deep neural network based algorithm., (© 2023. The Author(s).)

Objectives: Stroke patients suffer from ankle joint deformities due to spastic ankle muscles. This study evaluated the viability of using 3D scanned surface images of the feet of stroke victims to visually assess the deformities of a hemiparetic foot and investigated the influences of deformed ankle joints on gait kinematics., Methods: A total of 30 subjects with stroke-induced hemiparesis and 11 age-matched healthy controls completed the clinical assessments. We analyzed their feet's morphometric characteristics using a 3D scanner, identified convenient anthropometric measurements, and conducted gait trials on even and uneven terrains. The 3D foot morphometric characteristics were evaluated using the geometric morphometrics method (GMM)., Results: Results showed that there were significant differences in bilateral foot shapes between the chronic stroke patients and healthy controls and between the paretic and non-paretic sides in the chronic stroke patients. In stroke patients, those with the smaller medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of dorsi-/plantar flexion during gaits on uneven terrains ( p = 0.009). In addition, those with the greater medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of inversion/eversion during gaits on even and uneven terrains ( p < 0.05)., Conclusion: Using 3D scanning technology, bilateral morphometric changes in the feet of chronic stroke patients were shown by GMM and the simple anthropometric measurements identified its shape deformities in the feet. Their possible effects on gait kinematics while walking on uneven terrains were investigated. Current methodology can be potentially useful in applying conventional productions of clinically manufactured, patient-fitted ankle-foot-orthosis in orthotics and prosthetics, and in detecting various unidentified pathological deformities in the feet., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Cho, Seo and Lee.)

Techniques to study brain activities have evolved dramatically, yet tremendous challenges remain in acquiring high-throughput electrophysiological recordings minimally invasively. Here, we develop an integrated neuroelectronic array that is filamentary, high-density and flexible. Specifically, with a design of single-transistor multiplexing and current sensing, the total 256 neuroelectrodes achieve only a 2.3 × 0.3 mm2 area, unprecedentedly on a flexible substrate. A novel single-transistor multiplexing acquisition circuit further reduces noise from the electrodes, decreased the footprint of each pixel, and potentially increased the device lifetime. The filamentary neuroelectronic array also integrates with a rollable contact pad design, allowing the device to be injected through a syringe, enabling potential minimally invasive array delivery. Successful acute auditory experiments in rats validate the ability of the array to record neural signals with high tone decoding accuracy. Together, these results establish soft, high-density neuroelectronic arrays as promising devices for neuroscience research and clinical applications., Competing Interests: Competing Interest Statement The authors declare no competing interest.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed a serious threat to global public health. A novel vaccine made from messenger RNA (mRNA) has been developed and approved for use at an unprecedented pace. However, an increased risk of myocarditis has been reported after BNT162b2 mRNA vaccination due to unknown causes. In this study, we used single-cell RNA sequencing and single-cell T cell receptor sequencing analyses of peripheral blood mononuclear cells (PBMCs) to describe, for the first time, changes in the peripheral immune landscape of a patient who underwent myocarditis after BNT162b2 vaccination. The greatest changes were observed in the transcriptomic profile of monocytes in terms of the number of differentially expressed genes. When compared to the transcriptome of PBMCs from vaccinated individuals without complications, increased expression levels of IL7R were detected in multiple cell clusters. Overall, results from this study can help advance research into the pathogenesis of BNT162b2-induced myocarditis.

Brain computer interfaces (BCIs) provide clinical benefits including partial restoration of lost motor control, vision, speech, and hearing. A fundamental limitation of existing BCIs is their inability to span several areas (> cm 2 ) of the cortex with fine (<100 μm) resolution. One challenge of scaling neural interfaces is output wiring and connector sizes as each channel must be independently routed out of the brain. Time division multiplexing (TDM) overcomes this by enabling several channels to share the same output wire at the cost of added noise. This work leverages a 130-nm CMOS process and transfer printing to design and simulate a 384-channel actively multiplexed array, which minimizes noise by adding front end filtering and amplification to every electrode site (pixel). The pixels are 50 μm × 50 μm and enable recording of all 384 channels at 30 kHz with a gain of 22.3 dB, noise of 9.57 μV rms, bandwidth of 0.1 Hz - 10 kHz, while only consuming 0.63 μW/channel. This work can be applied broadly across neural interfaces to create high channel-count arrays and ultimately improve BCIs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dangerous threat to public health worldwide for the last few years, which led to the development of the novel mRNA vaccine (BNT162b2). However, BNT162b2 vaccination is known to be associated with myocarditis. Here, as an attempt to determine the pathogenesis of the disease and to develop biomarkers to determine whether subjects likely proceed to myocarditis after vaccination, we conducted a time series analysis of peripheral blood mononuclear cells of a patient with BNT162b2-induced myocarditis. Single-cell RNA sequence analysis identified monocytes as the cell clusters with the most dynamic changes. To identify distinct gene expression signatures, we compared monocytes of BNT162b2-induced myocarditis with monocytes under various conditions, including SARS-CoV-2 infection, BNT162b2 vaccination, and Kawasaki disease, a disease similar to myocarditis. Representative changes in the transcriptomic profile of classical monocytes include the upregulation of genes related to fatty acid metabolism and downregulation of transcription factor AP-1 activity. This study provides, for the first time, the importance of classical monocytes in the pathogenesis of myocarditis following BNT162b2 vaccination and presents the possibility that vaccination affects monocytes, further inducing their differentiation and infiltration into the heart., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hwang, Huh, Bu, Seo, Kwon, Kim, Yoon, Ahn and Fang.)

The endoscopic findings of diffuse large B cell lymphoma have various presentations. In our case, the patient had developed multiple elevated central ulceration lesions, and the peripheral elevated portion had a heaped-up margin. The margin had a sharp, smooth edge that was not infiltrative and could be confused with a simple gastric ulcer. Endoscopists should be aware of the possibility of multiple lymphoma ulcers with heaped-up margins. We present some unusual endoscopic features of lymphoma, which are easily misdiagnosed as gastric ulcers.

Background and Objectives: The prediction of the prognosis and effect of neoadjuvant therapy is vital for patients with advanced or unresectable colorectal carcinoma (CRC). Materials and Methods : We investigated several tumor microenvironment factors, such as intratumoral budding (ITB), desmoplastic reaction (DR), and Klintrup-Mäkinen (KM) inflammation grade, and the tumor-stroma ratio (TSR) in pretreatment biopsy samples (PBSs) collected from patients with advanced or unresectable CRC. A total of 85 patients with 74 rectal carcinomas and 11 colon cancers treated at our hospital were enrolled; 66 patients had curative surgery and 19 patients received palliative treatment. Results: High-grade ITB was associated with recurrence ( p = 0.002), death ( p = 0.034), and cancer-specific death ( p = 0.034). Immature DR was associated with a higher grade of clinical tumor-node-metastasis stage (cTNM) ( p = 0.045), cN category ( p = 0.045), and cM category ( p = 0.046). The KM grade and TSR were not related to any clinicopathological factors. High-grade ITB had a significant relationship with tumor regression in patients who received curative surgery ( p = 0.049). Conclusions: High-grade ITB in PBSs is a potential unfavorable prognostic factor for patients with advanced CRC. Immature DR, TSR, and KM grade could not predict prognosis or therapy response in PBSs.

Background: Volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) is an advanced form of radiotherapy (RT) technology. The purpose of this study was to report long-term treatment outcomes in patients with locally advanced rectal cancer undergoing VMAT-SIB based concurrent chemoradiotherapy (CRT)., Methods: Between January 2016 and January 2018, a total of 22 patients with operable stage II-III rectal adenocarcinoma were recruited for the pre-designed VMAT-SIB RT protocol. All patients underwent standard diagnostic and staging work-up. The RT target volumes included the following areas: PTV1 = mesorectum that contained gross tumors and enlarged lymph node regions and PTV2 = mesorectum and regional lymphatics from L4-5/S1 to 3-4 cm below the tumor or levator ani muscle, excluding PTV1. The VMAT-SIB dose prescription was as follows: PTV1 = 52.5 Gy/daily 2.1 Gy/25 fractions, PTV2 = 45 Gy/daily 1.8 Gy/25 fractions., Results: The mean age of the study population was 64 (range, 18-84) years, and 15 (68.2%) patients were male. Radical operation (total mesorectal excision) was performed by either low anterior resection, ultralow anterior resection, or abdominal perineal resection. All five (22.7%) of the patients with confirmed increasing serum carcinoembryonic antigen (CEA) level at diagnosis showed normalization of serum CEA level after the planned treatment. Among 20 patients who underwent preoperative CRT and surgery, tumor down staging in T- and N-stages was achieved in 10 patients (50%) and 13 patients (65%), respectively, with 20% of ypT0/Tis. With a median follow-up of 54.2 (range, 22.6-61.1) months, the 5-year disease-free survival, overall survival, and local control rates were 64.6%, 81.8%, and 84.4%, respectively. Five patients developed distant metastasis and one developed local recurrence as a first event. Two cases with anastomosis site leakage, three with adhesive ileus, and two with abscess formation were observed during postoperative periods., Conclusions: The current VMAT-SIB-based CRT protocol provided acceptable treatment and toxicity outcomes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Dong Soo Lee et al.)

Due to the increased morbidity and mortality by fungal infections and the emergence of severe antifungal resistance, there is an urgent need for new antifungal agents. Here, we screened for antifungal activity in our in-house library through the minimum inhibitory concentration test and derived two hit compounds with moderate antifungal activities. The hit compounds' antifungal activities and drug-like properties were optimized by substituting various aryl ring, alkyl chain, and methyl groups. Among the optimized compounds, 22h was the most promising candidate with good drug-like properties and exhibited potent fast-acting fungicidal antifungal effects against various fungal pathogens and synergistic antifungal activities with some known antifungal drugs. Additionally, 22h was further confirmed to disturb fungal cell wall integrity by activating multiple cell wall integrity pathways. Furthermore, 22h exerted significant antifungal efficacy in both the subcutaneous infection mouse model and ex vivo human nail infection model.

Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of PARP is inconsistent in studies of various cancers. In the present study, we conducted a systematic review and meta-analysis to reveal the prognostic and clinicopathological significance of PARP expression in multiple solid cancers. We searched the MEDLINE, EMBASE, and Cochrane databases for relevant research articles published from 2005 to 2021. The pooled hazard ratio (HR) with confidence interval (CI) was calculated to investigate the relationship between PARP expression and survival in multiple solid cancers. In total, 10,667 patients from 31 studies were included. A significant association was found between higher PARP expression and overall survival (OS) (HR = 1.54, 95% CI = 1.34-1.76, p < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10-1.21, p < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03-1.08, p < 0.001). Subgroup analyses showed that PARP overexpression was significantly related to poor OS in patients with breast cancers (HR = 1.38, 95% CI = 1.28-1.49, p < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10-1.33, p = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29-3.45, p = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94-5.58, p < 0.001). Regarding ethnicity, Asian people have almost twice their worst survival rate compared to Caucasians. The pooled odds ratio analysis showed a significant relationship between higher PARP expression and larger tumour size, poor tumour differentiation, lymph node metastasis, distant metastasis, higher TNM stage and lymphovascular invasion, and positive immunoreactivity for Ki-67, BRCA1, and BRCA2. In addition, nuclear expression assessed by the QS system using Abcam and Santa Cruz Biotechnology seems to be the most commonly used and reproducible IHC method for assessing PARP expression. This meta-analysis revealed that higher PARP expression was associated with a worse OS, DFS, and PFS in patients with solid cancers. Moreover, inhibition of this pathway through its specific inhibitors may extend the survival of patients with higher PARP expression.

Thin-film polymer microelectrode arrays (MEAs) facilitate the high-resolution neural recording with its superior mechanical compliance. However, the densely packed electrodes and interconnects along with the ultra-thin polymeric encapsulation/substrate layers give rise to non-negligible crosstalk, which could result in severe interference in the neural signal recording. Due to the lack of standardized characterization or modeling of crosstalk in neural electrode arrays, to date, crosstalk in polymer MEAs remains poorly understood. In this work, the crosstalk between two adjacent polymer microelectrodes is measured experimentally and modeled using equivalent circuits. Importantly, this study demonstrated a two-well measuring platform and systematically characterized the crosstalk in polymer microelectrodes with true isolation of the victim channel and precise control of its grounding condition. A simple, unified equation from detailed circuit modeling was proposed to calculate the crosstalk in different environments. Finite element analysis (FEA) analysis was conducted further to explore the crosstalk in more aggressively scaled polymer electrode threads. In addition to standardizing neural electrode array crosstalk characterization, this study not only reveals the dependence of the crosstalk in polymer MEAs on a variety of key device parameters but also provides general guidelines for the design of thin polymer MEAs for high-quality neural signal recording., Competing Interests: The authors declare no competing financial interests.

Background: Endoscopic removal of large and thick-stalked pedunculated colonic polyps, often leads to massive hemorrhage. Several techniques to minimize this complication have not been widely adopted due to some caveats. In order to prevent postpolypectomy bleeding, we invented a novel technique to dissect long-stalked pedunculated colonic polyps using endoscopic band ligation (EBL) by laterally approaching the stalk., Methods: In this prospective single-center study, 17 pedunculated polyps in 15 patients were removed between April 2012 and January 2016. We targeted pedunculated polyps with a long stalk length (>10 mm) and a large head (>10 mm) located in the distal colon. After identifying lesions with a colonoscope, we reapproached the middle part of the stalk of the targeted polyp with an EBL-equipped gastroscope to ligate it. Snare polypectomy was performed just above the ligation site of the stalk., Results: EBL-assisted polypectomy removed all of the lesions successfully, which were confirmed pathologically. There was little technical difficulty associated with the endoscopic procedures, regardless of polyp size and stalk thickness, except for one case with a very large polyp that impeded the visualization of the ligation site. We observed a positive correlation between procedure time and the diameter of the head (spearman ρ = 0.52, P = 0.034). After dissection of the polyp, the EBL bands remained fastened to the dissected stalks in all cases. There was no complication associated with polypectomy for 1 month., Conclusion: EBL-assisted polypectomy is an easy, safe, and effective technique to remove long-stalked pedunculated colonic polyps without postpolypectomy bleeding., Competing Interests: None

Neural interfaces bridge the nervous system and the outside world by recording and stimulating neurons. Combining electrical and optical modalities in a single, hybrid neural interface system could lead to complementary and powerful new ways to explore the brain. It has gained robust and exciting momentum recently in neuroscience and neural engineering research. Here, we review developments in the past several years aiming to achieve such hybrid electrical and optical microsystem platforms. Specifically, we cover three major categories of technological advances: transparent neuroelectrodes, optical neural fibers with electrodes, and neural probes/grids integrating electrodes and microscale light-emitting diodes. We discuss examples of these probes tailored to combine electrophysiological recording with optical imaging or optical neural stimulation of the brain and possible directions of future innovation.

Commercial mineral trioxide aggregate (MTA) materials such as Endocem MTA (EC), Dia-Root Bio MTA (DR), RetroMTA (RM), and ProRoot MTA (PR) are increasingly used as root-end filling materials. The aim of this study was to assess and compare the physicochemical and mechanical properties and cytotoxicity of these MTAs. The film thicknesses of EC and DR were considerably less than that of PR; however, RM's film thickness was greater than that of PR. In addition, the setting times of EC, DR, and RM were shorter than that of PR ( p < 0.05). The solubility was not significantly different among all groups. The three relatively new MTA groups (EC, DR, and RM) exhibited a significant difference in pH variation and calcium ion release relative to the PR group ( p < 0.05). The radiopacity of the three new MTAs was considerably less than that of PR. The mechanical strength of RM was not significantly different from that of PR ( p > 0.05); however, the EC and DR groups were not as strong as PR ( p < 0.05). All MTA groups revealed cytocompatibility. In conclusion, the results of this study confirmed that EC, RM, DR, and PR exhibit clinically acceptable physicochemical and mechanical properties and cell cytotoxicity.

Background: There are few reports of cervical myelopathy caused by an attack of subaxial calcium pyrophosphate dihydrate (CPPD) deposition. Moreover, there has been no report on cervical myelopathy by subaxial CPPD deposition with simultaneous asymptomatic crowned dens syndrome (CDS) at the same time., Case Presentation: The first case was a 68-year-old male complaining of cervical myelopathic symptoms. Plain radiographs, computed tomography (CT) and magnetic resonance imaging (MRI) findings revealed spinal cord compression by calcified round lesions at C4 as well as a calcified lesion behind the dens. The second case was a 77-year-old female complaining of cervical myelopathic symptoms. Plain radiographs, CT and MRI findings revealed spinal cord compression by calcified round lesions at C3 and C4 as well as a calcified lesion behind the dens. In both cases, we believed that the calcified lesion behind the dens was an asymptomatic lesion. Therefore, the first patient received decompressive laminectomy of C3 and C4, removal of calcified round lesions, and posterior fixation from C3 to C5 due to associated kyphosis. The second patient underwent decompressive laminectomy of C3 and C4 and removal of calcified round lesions. Microscopic examination under polarized light showed dark blue calcifications with rhomboid crystals that were positively birefringent. The findings were consistent with those of CPPD., Conclusions: This is the first study to report cervical myelopathy caused by subaxial CPPD deposition with simultaneous asymptomatic CDS. Surgical removal of the subaxial CPPD deposition alone achieved a satisfactory surgical outcome without recurrence.

Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases in Cryptococcus neoformans, a fungal pathogen that causes life-threatening fungal meningoencephalitis. We analyse 230 signature-tagged mutant strains for 114 putative phosphatases under 30 distinct in vitro growth conditions, revealing at least one function for 60 of these proteins. Large-scale virulence and infectivity assays using insect and mouse models indicate roles in pathogenicity for 31 phosphatases involved in various processes such as thermotolerance, melanin and capsule production, stress responses, O-mannosylation, or retromer function. Notably, phosphatases Xpp1, Ssu72, Siw14, and Sit4 promote blood-brain barrier adhesion and crossing by C. neoformans. Together with our previous systematic studies of transcription factors and kinases, our results provide comprehensive insight into the pathobiological signalling circuitry of C. neoformans.

Histiocytic sarcoma (HS) is a comparatively rare hematolymphoid neoplasm. Differential diagnosis of this entity has generally been proven to be so difficult that extensive immunohistochemical staining is required to confirm its presence. We herein present a case of HS manifesting as a retroperitoneal mass in which imprint cytology (IC) contributed to the diagnosis. A 77-year-old man was referred for the evaluation of a colonic tubulovillous polypoid lesion. Preoperative imaging revealed a 3 cm-sized polypoid lesion in the transverse colon. Incidentally, a retroperitoneal mass of 8 cm in the left para-aortic region was also detected. Diff-Quik stained IC slides were prepared as an adjunct to intraoperative pathology consultation. The smear exhibited moderate cellularity involving loosely cohesive cell clusters with intervening delicate vasculature. Most of the tumor cells consisted of large single cells with abundant eosinophilic cytoplasm that was vacuolated and foamy. The nuclei were predominantly large and eccentrically located. Mitotic figures were minimal in number and finely granular brown pigments were occasionally observed. A frozen section diagnosis was reported as a malignant neoplasm, and a histologic diagnosis of HS was confirmed by conducting a battery of immunohistochemical stains: negative for pan-cytokeratin, EMA, CD117, HMB45, Melan A, CD30, PAX5, CD20, S-100, and CD23 but strong positive for vimentin and CD68. This entity is rarely described in terms of cytopathologic features. This case study highlights how cytopathologists should be aware of HS as a retroperitoneal lesion and should become familiar with cytomorphologic features., (© 2020 Wiley Periodicals, Inc.)