Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients.

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22-09.

BACKGROUND: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. METHODS: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. DISCUSSION: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. TRIAL REGISTRATION: NCT05525858.

Timing, velocity, and magnitude of pubertal changes in body composition: a longitudinal study.

BACKGROUND: Pubertal changes in body composition significantly influence future health, with links to various diseases. This study aimed to evaluate the weight changes, fat-free mass (FFM), and body fat mass (BFM) during pubertal growth in Korean children and adolescents. METHODS: We utilized mixed longitudinal data, employing bioelectrical impedance analysis for 4641 height measurements (2204 boys, 2437 girls) from 361 individuals (170 boys, 191 girls) aged 7-18 years. Utilizing the Superimposition by Translation and Rotation (SITAR) model, a shape-invariant growth curve model, reference curves for height, weight, and body composition change velocities were estimated. RESULTS: Korean boys experience peak weight velocity (PWV) at an average age of 12.41 years, with a rate of 8.19 kg/year, peak fat-free mass velocity (PFFV) at 12.70 years (7.60 kg/year), and peak body fat mass velocity (PBFV) at 9.69 years (2.67 kg/year). Korean girls show PWV at 11.28 years (6.33 kg/year), PFFV at 11.13 years (4.86 kg/year), and PBFV at 12.33 years (2.72 kg/year). Positive correlations exist among the ages of peak height velocity, PWV, PFFV, and PBFV. CONCLUSIONS: This research represents the groundbreaking application of the SITAR model in analyzing changes in body composition during pubertal growth in Korean children and adolescents. IMPACT: This study utilized the SITAR model to analyze longitudinal changes in the body composition of the general pediatric population in Korea across pre- and post-pubertal stages, addressing overlooked aspects in cross-sectional studies. Examining growth parameters, including size (mean mass), tempo (timing), and velocity (compression and expansion) for each body component, revealed positive correlations among ages at peak velocities for various body composition parameters. This study can be employed for further investigations that compare the tempo, size, and velocity of various body composition parameters in pediatric disease cohorts and the general population.

Configurable Crack Wall Conduction in a Complex Oxide.

Mobile defects in solid-state materials play a significant role in memristive switching and energy-efficient neuromorphic computation. Techniques for confining and manipulating point defects may have great promise for low-dimensional memories. Here, we report the spontaneous gathering of oxygen vacancies at strain-relaxed crack walls in SrTiO3 thin films grown on DyScO3 substrates as a result of flexoelectricity. We found that electronic conductance at the crack walls was enhanced compared to the crack-free region, by a factor of 104. A switchable asymmetric diode-like feature was also observed, and the mechanism is discussed, based on the electrical migration of oxygen vacancy donors in the background of Sr-deficient acceptors forming n+-n or n-n+ junctions. By tracing the temporal relaxations of surface potential and lattice expansion of a formed region, we determine the diffusivity of mobile defects in crack walls to be 1.4 × 10-16 cm2/s, which is consistent with oxygen vacancy kinetics.

Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

Automated Detection of Maxillary Sinus Opacifications Compatible with Sinusitis from CT Images.

BACKGROUND: Sinusitis is a commonly encountered clinical condition that imposes a considerable burden on the healthcare systems. A significant number of maxillary sinus opacifications are diagnosed as sinusitis, often overlooking the precise differentiation between cystic formations and inflammatory sinusitis, resulting in inappropriate clinical treatment. This study aims to improve diagnostic accuracy by investigating the feasibility of differentiating maxillary sinusitis, retention cysts, and normal sinuses. METHODS: We developed a deep learning-based automatic detection model to diagnose maxillary sinusitis using ostiomeatal unit computed tomography images. Of the 1080 randomly selected coronal-view CT images, including 2158 maxillary sinuses, datasets of maxillary sinus lesions comprised 1138 normal sinuses, 366 cysts, and 654 sinusitis based on radiographic findings, and were divided into training (n = 648 CT images), validation (n = 216), and test (n = 216) sets. We utilized a You Only Look Once based model for object detection, enhanced by the transfer learning method. To address the insufficiency of training data, various data augmentation techniques were adopted, thereby improving the model's robustness. RESULTS: The trained You Only Look Once version 8 nano (YOLOv8n) model achieved an overall precision of 97.1%, with the following class precisions on the test set: normal = 96.9%, cyst = 95.2%, and sinusitis = 99.2%. With an average F1 score of 95.4%, the F1 score was the highest for normal, then sinusitis, and finally, cysts. Upon evaluating a performance on difficulty level, the precision decreased to 92.4% on challenging test dataset. CONCLUSIONS: The developed model is feasible for assisting clinicians in screening maxillary sinusitis lesions.

Novel Mg- and Ga-doped ZnO/Li-Doped Graphene Oxide Transparent Electrode/Electron-Transporting Layer Combinations for High-Performance Thin-Film Solar Cells.

Herein, a novel combination of Mg- and Ga-co-doped ZnO (MGZO)/Li-doped graphene oxide (LGO) transparent electrode (TE)/electron-transporting layer (ETL) has been applied for the first time in Cu2 ZnSn(S,Se)4 (CZTSSe) thin-film solar cells (TFSCs). MGZO has a wide optical spectrum with high transmittance compared to that with conventional Al-doped ZnO (AZO), enabling additional photon harvesting, and has a low electrical resistance that increases electron collection rate. These excellent optoelectronic properties significantly improved the short-circuit current density and fill factor of the TFSCs. Additionally, the solution-processable alternative LGO ETL prevented plasma-induced damage to chemical bath deposited cadmium sulfide (CdS) buffer, thereby enabling the maintenance of high-quality junctions using a thin CdS buffer layer (≈30 nm). Interfacial engineering with LGO improved the Voc of the CZTSSe TFSCs from 466 to 502 mV. Furthermore, the tunable work function obtained through Li doping generated a more favorable band offset in CdS/LGO/MGZO interfaces, thereby, improving the electron collection. The MGZO/LGO TE/ETL combination achieved a power conversion efficiency of 10.67%, which is considerably higher than that of conventional AZO/intrinsic ZnO (8.33%).

Development and Verification of a Diagnostic Technology for Waste Battery Deterioration Factors.

We defined four major deterioration factors (electrolyte loss (EL), lithium loss (LL), lithium precipitation (LP), and compound deterioration (CD)). Then, we derived eleven key performance indicators (KPIs) for comparative analysis. After that, we fabricated three deteriorated cells for each of three deterioration factors (EL, LL, and LP) and one cell with CD (for verification) with four individual (dis)charging experiment manuals. The two major contributions of this study are the performance of 1) trend analysis to determine a suitable diagnostic metric by inspecting the eleven KPIs and 2) comparison analysis of V o c v , t ' ' ${{V}_{ocv,t}^{{ {^\prime} {^\prime}}}}$ and V o c v , t , s i m ' ' ${{V}_{ocv,t,sim}^{{ {^\prime} {^\prime}}}}$ to verify the effectiveness of utilizing V o c v , t ' ' ${{V}_{ocv,t}^{{ {^\prime} {^\prime}}}}$ as a real-time deterioration diagnostic factor using a concept of model-in-the-loop simulation. The results show that 1) V o c v , t ' ' ${{V}_{ocv,t}^{{ {^\prime} {^\prime}}}}$ has the most conspicuous trendline tendency among the eleven comparison targets for all four major deterioration factors, and 2) the angle difference between the two trends of V o c v , t ' ' ${{V}_{ocv,t}^{{ {^\prime} {^\prime}}}}$ and V o c v , t , s i m ' ' ${{V}_{ocv,t,sim}^{{ {^\prime} {^\prime}}}}$ lies within a minimum of 9° and a maximum of 43° (with a 10 4 ${{10}^{4}}$ sscale on the x-axis and a 10 - 7 ${{10}^{-7}}$ scale on the y-axis for a clear trend line analysis). From this, we can conclude that the trendline-based real-time deterioration analysis employing V o c v , t ' ' ${{V}_{ocv,t}^{{ {^\prime} {^\prime}}}}$ may be practically applicable to a limited extent.

Auxiliary liver xenotransplantation technique in a transgenic pig-to-non-human primate model: A surgical approach to prolong survival.

Xenotransplantation using pigs' liver offers a potentially alternative method to overcome worldwide donor shortage, or more importantly as a bridge to allotransplantation. However, it has been challenged by profound thrombocytopenia and fatal coagulopathy in non-human primate models. Here we suggest that a left auxiliary technique can be a useful method to achieve extended survival of the xenograft. Fifteen consecutive liver xenotransplants were carried out in a pig-to-cynomolgus model. Right auxiliary technique was implemented in two cases, orthotopic in eight cases, and left auxiliary in five cases. None of the right auxiliary recipients survived after surgery due to hemorrhage during complex dissection between the primate's right lobe and inferior vena cava. Orthotopic recipients survived less than 7 days secondary to profound thrombocytopenia and coagulopathy. Two out of five left auxiliary xenotransplants survived more than 3 weeks without uncontrolled thrombocytopenia or anemia, with one of them surviving 34 days, the longest graft survival reported to date. Left auxiliary xenotransplant is a feasible approach in non-human primate experiments, and the feared risk of thrombocytopenia and coagulopathy can be minimized. This may allow for longer evaluation of the xenograft and help better understand histopathological and immunological changes that occur following liver xenotransplantation.

A Deep Reinforcement Learning Strategy for Surrounding Vehicles-Based Lane-Keeping Control.

As autonomous vehicles (AVs) are advancing to higher levels of autonomy and performance, the associated technologies are becoming increasingly diverse. Lane-keeping systems (LKS), corresponding to a key functionality of AVs, considerably enhance driver convenience. With drivers increasingly relying on autonomous driving technologies, the importance of safety features, such as fail-safe mechanisms in the event of sensor failures, has gained prominence. Therefore, this paper proposes a reinforcement learning (RL) control method for lane-keeping, which uses surrounding object information derived through LiDAR sensors instead of camera sensors for LKS. This approach uses surrounding vehicle and object information as observations for the RL framework to maintain the vehicle's current lane. The learning environment is established by integrating simulation tools, such as IPG CarMaker, which incorporates vehicle dynamics, and MATLAB Simulink for data analysis and RL model creation. To further validate the applicability of the LiDAR sensor data in real-world settings, Gaussian noise is introduced in the virtual simulation environment to mimic sensor noise in actual operational conditions.

C2RL: Convolutional-Contrastive Learning for Reinforcement Learning Based on Self-Pretraining for Strong Augmentation.

Reinforcement learning agents that have not been seen during training must be robust in test environments. However, the generalization problem is challenging to solve in reinforcement learning using high-dimensional images as the input. The addition of a self-supervised learning framework with data augmentation in the reinforcement learning architecture can promote generalization to a certain extent. However, excessively large changes in the input images may disturb reinforcement learning. Therefore, we propose a contrastive learning method that can help manage the trade-off relationship between the performance of reinforcement learning and auxiliary tasks against the data augmentation strength. In this framework, strong augmentation does not disturb reinforcement learning and instead maximizes the auxiliary effect for generalization. Results of experiments on the DeepMind Control suite demonstrate that the proposed method effectively uses strong data augmentation and achieves a higher generalization than the existing methods.

Gintonin-Induced Wound-Healing-Related Responses Involve Epidermal-Growth-Factor-like Effects in Keratinocytes.

Epidermal growth factor (EGF) receptor activation and related downstream signaling pathways are known to be one of the major mechanisms of the proliferation and migration of keratinocytes. The heparin-binding EGF-like growth factor (HB-EGF) binds to EGF receptors and stimulates keratinocyte proliferation and migration. Gintonin, a novel ginseng compound, is a lysophosphatidic acid (LPA) receptor ligand. Gintonin has skin-wound-healing effects. However, the underlying mechanisms for these gintonin actions remain unclear. In this study, we aimed to elucidate the involvement of EGFRs in gintonin-induced wound repair in HaCaT keratinocytes. In this study, a water-soluble tetrazolium salt-based assay, a modified Boyden chamber migration assay, and immunoblotting were performed. Gintonin increased EGF receptor activation in HaCaT cells. However, the gintonin-induced phosphorylation of the EGF receptor was markedly reduced via treatment with the LPA inhibitor Ki16425 or the EGF receptor inhibitor erlotinib. Gintonin-enhanced proliferation and migration were blocked by the EGF receptor inhibitors (erlotinib and AG1478). Additionally, gintonin stimulated the expression and release of HB-EGF in HaCaT cells. EGF receptor inhibitors blocked gintonin-enhanced HB-EGF expression. These results indicate that the wound-healing effects of gintonin are closely related to the collaboration between EGF receptor activation and HB-EGF release-mediated downstream signaling pathways.

Gintonin Alleviates HCl/Ethanol- and Indomethacin-Induced Gastric Ulcers in Mice.

Gintonin, newly extracted from ginseng, is a glycoprotein that acts as an exogenous lysophosphatidic acid (LPA) receptor ligand. This study aimed to demonstrate the in vivo preventive effects of gintonin on gastric damage. ICR mice were randomly assigned to five groups: a normal group (received saline, 0.1 mL/10 g, p.o.); a control group (administered 0.3 M HCl/ethanol, 0.1 mL/10 g, p.o.) or indomethacin (30 mg/kg, p.o.); gintonin at two different doses (50 mg/kg or 100 mg/kg, p.o.) with either 0.3 M HCl/ethanol or indomethacin; and a positive control (Ranitidine, 40 mg/kg, p.o.). After gastric ulcer induction, the gastric tissue was examined to calculate the ulcer index. The expression of gastric damage markers, such as tumor necrosis factor (TNF)-α, cyclooxygenase 2 (COX-2), and LPA2 and LPA5 receptors, were measured by Western blotting. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay. The platelet endothelial cell adhesion molecule (PECAM-1), Evans blue, and occludin levels in gastric tissues were measured using immunofluorescence analysis. Both HCl/ethanol- and indomethacin-induced gastric ulcers showed increased TNF-α, IL-6, Evans blue permeation, and PECAM-1, and decreased COX-2, PGE2, occludin, and LPA5 receptor expression levels. However, oral administration of gintonin alleviated the gastric ulcer index induced by HCl/ethanol and indomethacin in a dose-dependent manner. Gintonin suppressed TNF-α and IL-6 expression, but increased COX-2 expression and PGE2 levels in mouse gastric tissues. Gintonin intake also increased LPA5 receptor expression in mouse gastric tissues. These results indicate that gintonin can play a role in gastric protection against gastric damage induced by HCl/ethanol or indomethacin.

High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration.

BACKGROUND: Relationship between cancer cell glycolysis and the landscape of tumor immune microenvironment in human cancers was investigated. METHODS: Forty-one fresh lung adenocarcinoma (ADC) tissues were analyzed using flow cytometry for comprehensive immunoprofiling. Formalin-fixed tissues were immunostained for hexokinase-2 (HK2) to assess cancer cell glycolysis. For validation, formalin-fixed tissues from 375 lung ADC, 118 lung squamous cell carcinoma (SqCC), 338 colon ADC, and 78 lung cancer patients treated with anti-PD-1/PD-L1 immunotherapy were immunostained for HK2, CD8, and FOXP3. RESULTS: Based on immunoprofiling of lung ADC, HK2 tumor expression was associated with the composition of lymphoid cells rather than myeloid cells. High HK2 tumor expression was associated with immunosuppressive/pro-tumorigenic features, especially decreased ratio of CD8 + T-cells to Tregs (rho = -0.415, P = 0.012). This correlation was also confirmed in four different cohorts including lung ADC and SqCC, colon ADC, and the immunotherapy cohort (rho = -0.175~-0.335, all P < 0.05). A low CD8 + T-cell to Treg ratio was associated with poor progression-free survival and overall survival in lung SqCC patients, and a shorter overall survival in the immunotherapy cohort (all, P < 0.05). CONCLUSION: An increase in HK2 expression may contribute to shaping the immunosuppressive/pro-tumorigenic tumor microenvironment by modulating the CD8 + T-cell to Treg ratio. Targeting tumor HK2 expression might be a potential strategy for enhancing anti-tumor immunity.

Clinicogenomic Characteristics and Treatment of Young-Onset Colorectal Cancer Patients Treated With Palliative Therapy in Real-World Practice.

INTRODUCTION: Young-onset colorectal cancer (YOCR) is increasing. This study aimed to determine the difference between advanced YOCR and non-YOCR patient outcomes. METHODS: We retrospectively included patients with recurrent/metastatic colorectal cancer treated with palliative systemic therapy between 2016 and 2018. Diagnosis at < 50 years was defined as YOCR. Targeted sequencing was used to assess the mutational status. RESULTS: Among the 969 patients included, 210 (21.7%) were YOCR. The median progression-free survival with first-line chemotherapy (PFS1) was 9.7 vs 9.4 months (P = .755), and the median overall survival (OS) was 25.9 vs 22.3 months (P = .581) in the YOCR and the non-YOCR group, respectively. However, the youngest patients diagnosed at < 30 years showed poorer survival outcomes (median PFS1, 3.9 months; median OS, 8.6 months) compared with other age groups. PFS1 did not differ between YOCR and non-YOCR by choice of treatment regimen. Among the 340 patients with targeted sequencing results, YOCR had fewer APC mutations (61% vs 80%), but had similar KRAS (53% vs 48%), NRAS (7% vs 3%), and BRAF class I mutations (4% vs 6%). The median tumor mutational burden (TMB) was 10.9 vs 12.5 mut/Mb in YOCR and non-YOCR patients, respectively (P = .064). TMB increased with age in tumors with high microsatellite instability (Pearson's R = .69, P = .028), but not in microsatellite-stable tumors (R = .02, P = .658). CONCLUSIONS: Survival outcomes with palliative systemic therapy were similar between recurrent/metastatic YOCR and non-YOCR with an age cut-off of 50 years. However, patients diagnosed at < 30 years of age showed poorer outcomes compared with other age groups.

Idiopathic Myointimal Hyperplasia of the Mesenteric Veins Is a Peculiar Venous Ischemia That May Be Diagnosed Before Surgery.

BACKGROUND: Idiopathic myointimal hyperplasia of the mesenteric veins is a segmental ischemia associated with noninflammatory hyperplasia of the intimal smooth muscle of the mesenteric veins. Owing to its rarity, timely diagnosis is often difficult. OBJECTIVE: The goal of this study was to improve clinical practice in terms of the diagnosis of idiopathic myointimal hyperplasia of the mesenteric veins. DESIGN: This was a retrospective observational study. SETTINGS: This study was conducted in a single institution with case collection from clinical archives. PATIENTS: Data from 12 cases of idiopathic myointimal hyperplasia of the mesenteric veins were retrieved from 2006-2020. Most patients were elderly men, with a male-to-female ratio of 10:1. MAIN OUTCOME MEASURES: Clinical, endoscopic, radiologic, and pathologic characteristics of idiopathic myointimal hyperplasia of the mesenteric veins served as outcome measures. RESULTS: Radiologically, marked segmental mural thickening and poor enhancement involved the sigmoid colon and rectum in most cases, with extension to the descending colon in some cases. Typical cases showed obliteration of the inferior mesenteric veins and collateral vessels. Colonoscopic findings were reminiscent of ischemia or ulcerative colitis, but sharp demarcation from the uninvolved segment was the most distinguishing feature. Surgically resected specimens showed marked segmental mural thickening, edema, and mucosal discoloration grossly. Microscopically, thick-walled, tortuous veins were observed mainly in the submucosa and subserosa, and the submucosa was markedly thickened in all cases. The subserosal large veins showed myointimal hyperplasia, and pericolic fat necrosis was invariably observed. The most useful histologic finding in biopsy material was tortuous, arteriolized mucosal capillaries with occasional fibrinoid necrosis. LIMITATIONS: This study was limited by its small number of cases and selection bias; there was also no prospective external validation. CONCLUSIONS: Radiologic and pathologic features of idiopathic myointimal hyperplasia of the mesenteric veins are distinct from those of ulcerative colitis or nonspecific ischemic colitis. Careful interpretation of endoscopic and radiologic images and generous biopsies with interpretation by experienced pathologists might lead to an early diagnosis and prevent unnecessary medical treatment. See Video Abstract at http://links.lww.com/DCR/B806. LA HIPERPLASIA MIOINTIMAL IDIOPTICA DE LAS VENAS MESENTRICAS ES UNA PECULIAR ISQUEMIA VENOSA QUE PUEDE DIAGNOSTICARSE ANTES DE LA CIRUGA: ANTECEDENTES:La hiperplasia miointimal idiopática de las venas mesentéricas es una isquemia segmentaria asociada con hiperplasia no inflamatoria del músculo liso de la íntima de las venas mesentéricas. Debido a su rareza, el diagnóstico oportuno suele ser difícil.OBJETIVO:Mejorar la práctica clínica con respecto al diagnóstico de hiperplasia miointimal idiopática de venas mesentéricas.DISEÑO:Estudio observacional retrospectivo.AJUSTES:Institución única, colección de casos de archivos clínicos.PACIENTES:Se recuperaron datos de 12 casos de hiperplasia miointimal idiopática de las venas mesentéricas durante el período 2006-2020. La mayoría de los pacientes eran hombres de edad avanzada, con una proporción de hombres a mujeres de 10:1.PRINCIPALES MEDIDAS DE RESULTADO:Características clínicas, endoscópicas, radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas.RESULTADOS:Radiológicamente, se vio marcado engrosamiento mural afectando de manera segmentaria y escaso realce que comprometieron al colon sigmoides y al recto en la mayoría de los casos, con extensión al colon descendente en algunos casos. Los casos típicos mostraron obliteración de las venas mesentéricas inferiores y vasos colaterales. Los hallazgos colonoscópicos recordaban a la isquemia o la colitis ulcerosa, pero la demarcación nítida del segmento no afectado fue la característica más distintiva. Las piezas quirúrgicas mostraron un marcado engrosamiento mural de manera segmentaria, edema y decoloración de la mucosa de forma macroscópica. Microscópicamente, se observaron venas tortuosas de paredes engrosadas principalmente en la submucosa y subserosa y la submucosa se encontraba marcadamente engrosada en todos los casos. Las grandes venas subserosas mostraban hiperplasia de la mioíntima e invariablemente se observaba necrosis grasa pericólica. El hallazgo histológico más útil en el material de biopsia fueron los tortuosos capilares arteriolizados de la mucosa con necrosis fibrinoide ocasional.LIMITACIONES:Pequeño número de casos; sesgo de selección; sin validación externa prospectiva.CONCLUSIONES:Las características radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas son distintas a las de la colitis ulcerosa o la colitis isquémica no específica. La interpretación cuidadosa de las imágenes endoscópicas y radiológicas y múltiples biopsias de manera generosa con la interpretación de patólogos experimentados pueden conducir a un diagnóstico temprano y prevenir tratamientos médicos innecesarios. Consulte Video Resumen en http://links.lww.com/DCR/B806. (Traducción-Dr Osvaldo Gauto).

Clinical Implication of Perineural and Lymphovascular Invasion in Rectal Cancer Patients Who Underwent Surgery After Preoperative Chemoradiotherapy.

BACKGROUND: Lymphovascular and perineural invasion are well-known negative prognostic indicators in rectal cancer, but previous studies on their significance are not consistent. OBJECTIVE: This study assessed the prognostic value of lymphovascular and perineural invasion in rectal cancer patients who received preoperative chemoradiotherapy followed by curative resection. DESIGN: This is a retrospective analysis. SETTING: This study was performed at a tertiary cancer center. PATIENTS: Rectal cancer patients who underwent curative resection after preoperative chemoradiotherapy between January 2000 and December 2010. MAIN OUTCOME MEASURES: The primary outcomes were disease-free survival and overall survival. The survival rates were estimated using Kaplan-Meier analysis, and group comparisons were conducted using a log-rank test. RESULTS: Of the 1156 included patients, 109 (9.4%) presented with lymphovascular invasion and 137 (11.9%) presented with perineural invasion. Lymphovascular and perineural invasion were associated with T and N downstaging after preoperative chemoradiotherapy ( p < 0.001). In the ypN0 patients, the 5-year disease-free survival rates were 70.8% and 78.5% ( p = 0.150) for the lymphovascular invasion and absent groups, respectively. In the perineural invasion group, the 5-year disease-free survival rate was 59.0% compared to 80.2% in the absent group ( p = 0.001). Among the ypN+ patients, the 5-year disease-free survival rates were 36.9% and 44.4% for the lymphovascular invasion and absent groups, respectively ( p = 0.211). The perineural invasion group had a poorer 5-year disease-free survival rate compared to the absent group (29.7% vs 46.7%; p = 0.011). By multivariable analyses, perineural invasion correlated with a poor disease-free survival (HR 1.412, 95% CI 1.082-1.843; p = 0.011) and also in ypN0 subgroup analysis (HR 1.717, 95% CI 1.093-2.697; p = 0.019). LIMITATIONS: This study was a retrospective study conducted at a single center. CONCLUSIONS: Perineural invasion is a reliable independent predictor of recurrence in rectal cancer patients treated with preoperative chemoradiotherapy. Patients with perineural invasion should be considered for closer surveillance even with ypN0 status. See Video Abstract at http://links.lww.com/DCR/B833 .IMPLICACIÓN CLÍNICA DE LA INVASIÓN PERINEURAL Y LINFOVASCULAR EN PACIENTES CON CÁNCER DE RECTO SOMETIDOS A CIRUGÍA DESPUÉS DE QUIMIORRADIOTERAPIA PREOPERATORIA. ANTECEDENTES: La invasión linfovascular y perineural en cancer de recto, son indicadores pronósticos negativos bien conocidos, pero estudios previos sobre su significancia, no son consistentes. OBJETIVO: El estudio evaluó el valor pronóstico de la invasión linfovascular y perineural en pacientes con cáncer de recto sometidos a quimiorradioterapia preoperatoria seguida de resección curativa. DISEO: Es un análisis retrospectivo. ENTORNO CLINICO: El estudio se realizó en un centro oncológico terciario. PACIENTES: Pacientes con cáncer de recto sometidos a resección curativa después de quimiorradioterapia preoperatoria entre enero de 2000 y diciembre de 2010. PRINCIPALES MEDIDAS DE VALORACION: Los resultados primarios fueron la supervivencia libre de enfermedad y la supervivencia general. Las tasas de supervivencia se estimaron mediante el análisis de Kaplan-Meier y las comparaciones de grupos se realizaron mediante una prueba de rango logarítmico. RESULTADOS: De los 1156 pacientes incluidos, 109 (9,4%) presentaron invasión linfovascular y 137 (11,9%) invasión perineural. La invasión linfovascular y perineural se asoció con reducción del estadio de T y N después de la quimiorradioterapia preoperatoria ( p < 0,001). En los pacientes ypN0, las tasas de supervivencia libre de enfermedad a 5 años fueron del 70,8% y el 78,5% ( p = 0,150) para los grupos con y sin invasión linfovascular, respectivamente. En el grupo de invasión perineural, la tasa de supervivencia libre de enfermedad a 5 años fue del 59,0%, en comparación con el 80,2% en el grupo ausente ( p = 0,001). Entre los pacientes ypN +, las tasas de supervivencia sin enfermedad a 5 años fueron del 36,9% y 44,4% para los grupos con y sin invasión linfovascular, respectivamente ( p = 0,211). El grupo de invasión perineural mostró una tasa de supervivencia libre de enfermedad a 5 años menor, en comparación con el grupo ausente (29,7% versus 46,7%, p = 0,011). Mediante análisis multivariable, la invasión perineural se correlacionó con una pobre tasa de supervivencia de enfermedad (índice de riesgo 1,412; intervalo de confianza del 95%: 1,082-1,843; p = 0,011) y también en el análisis de subgrupos ypN0 (índice de riesgo 1,717; intervalo de confianza del 95%: 1,093-2,697; p = 0,019). LIMITACIONES: Estudio retrospectivo realizado en un solo centro. CONCLUSIONES: La invasión perineural es un predictor independiente y confiable de recurrencia en pacientes con cáncer de recto tratados con quimiorradioterapia preoperatoria. Los pacientes con invasión perineural deben considerarse para una vigilancia más estrecha incluso con estadio ypN0. Consulte Video Resumen en http://links.lww.com/DCR/B833 . (Traducción-Dr. Fidel Ruiz Healy ).

Simple Ge/Si bilayer junction-based doping-less tunnel field-effect transistor.

Tunnel field-effect transistors (TFETs) have garnered great interest as an option for the replacement of metal-oxide-semiconductor field-effect transistors owing to their extremely low off-current and fast switching suitable for low-power-consumption applications. However, conventional doped TFETs have the disadvantage of introducing undesirable random dopant fluctuation (RDF) events, which cause a large variance in the threshold voltage and ambipolar leakage current at negative gate voltages. In this study, a simple approach for charge plasma-based doping-less TFETs (DL-TFETs), including the Ge/Si bilayer frame, which affects the RDF and low on-current issues, was developed by the commercially available Silvaco Atlas device simulator. The use of the Ge/Si bilayer enhances the on-current and point subthreshold swing to 1.4 × 10-6A and 16.6 mV dec-1, respectively. In addition, the dependencies of the Ge/Si junction boundary position and Ge content were examined systematically to attain a firm understanding of the electrical features in DL-TFETs.

Involvement of tissue changes induced by neoadjuvant treatment in total mesorectal excision (TME): novel suggestions for determining TME quality.

BACKGROUND: Few studies to date have investigated morphological changes after neoadjuvant treatment (NAT) and their implications in total mesorectal excision (TME). This study was primarily designed to evaluate whether tissue changes associated with NAT affected the quality of TME and additionally to suggest a more objective method evaluating TME quality. METHODS: This study enrolled 1322 consecutive patients who underwent curative robot-assisted surgery for rectal cancer. Patients who did and did not receive NAT were subjected to propensity-score matching, yielding 402 patients in each group. RESULTS: NAT independently reduced complete achievement of TME [odds ratio (OR) = 2.056, p = 0.017]. Intraoperative evaluation identified seven tissue changes significantly associated with NAT, including tumor perforation, mucin pool, necrosis, fibrosis, fat degeneration, and rectal or perirectal edema NAT (p < 0.001-0.05). Tumor perforation (OR = 5.299, p = 0.001) and mucin pool (OR = 14.053, p = 0.002) were independently associated with inappropriate (near-complete + incomplete) TME. Complete TME resulted in significantly reduced local recurrence (4.3% vs 15.3%, p = 0.003) and increased 5-year DFS rate (80.6% vs 67.6%, p = 0.047) compared with inappropriate one. By contrast, two tiers of complete and near-complete TMEs vs incomplete TME did not. Notably, among patients with complete TME, those who received NAT had a lower 5-year DFS than those who did not (77.8% vs 83.3%, p = 0.048). CONCLUSIONS: NAT-associated tissue changes, somewhat interrupting complete TME, may provide unsolved clue to the relative inability of NAT to improve overall survival. The conventional three-tier grading of TME seems to be simplified into two tiers as complete and inappropriate.

Assessment of log-based fingerprinting system of Mobius3D with Elekta linear accelerators.

PURPOSE: The purpose of this study was to investigate the matching error that occurs when the Mobius3D fingerprinting system is applied in conjunction with an Elekta linear accelerator (LINAC) and to offer an acceptable and alternative method for circumventing this problem. MATERIAL AND METHODS: To avoid the multileaf collimator (MLC) conflicting error in the Mobius3D fingerprinting system, we developed an in-house program to move the MLC in the Digital Imaging and Communications in Medicine (DICOM) radiotherapy (RT)-Plan to pertinent positions, considering the relationship between log data and planned data. The re-delivered log files were calculated in the Mobius3D system, and the results were compared with those of corrected data (i.e., we analyzed a pair of re-collected log data and the previous DICOM RT-Plan data). The results were then evaluated by comparing several items, such as point dose errors, gamma index (GI) passing rates, and MLC root-mean-square (RMS) values. RESULTS: For the point dose error, the maximum difference found was below 2.0%. In the case of GI analysis of all plans, the maximum difference in the passing rates was below 1.4%. The statistical results obtained using a paired Student's t-test showed that there were no significant differences within the uncertainty. In the case of the RMS test, the maximum difference found was approximately 0.08 mm. CONCLUSIONS: Our results showed that all the mismatched log files were sufficiently acceptable within the uncertainty. We conclude that the matching error obtained when applying Mobius3D to an Elekta LINAC may be addressed using a simple modification of the fingerprinting system, and we expect that our study findings will help vendors resolve this issue in the near future.