Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia.

OBJECTIVES: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. METHODS: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. RESULTS: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (IVL), small proline rich protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. CONCLUSIONS: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

An Unusual Presentation: High-Grade Serous Carcinoma of the Fallopian Tube Manifesting With Altered Mental Status Secondary to a Single Brain Metastasis-A Case Report and Review of the Literature.

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5 × 3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.

Methylated DNA Markers for Sporadic Colorectal and Endometrial Cancer Are Strongly Associated with Lynch Syndrome Cancers.

Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgical prophylaxis.To validate a panel of methylated DNA markers (MDM) previously identified in sporadic colorectal cancer and endometrial cancer for discrimination of these cancers in LS.In a case-control design, previously identified MDMs for the detection of colorectal cancer and endometrial cancer were assayed by qMSP on tissue-extracted DNA. Results were normalized to ACTB values within each sample. Least absolute shrinkage and selection operator models to classify colorectal cancer and endometrial cancer were trained on sporadic cases and controls and then applied to classify colorectal cancer and endometrial cancer, in those with LS, and cross-validated.We identified colorectal cancer cases (23 with LS, 48 sporadic), colorectal controls (32 LS, 48 sporadic), endometrial cancer cases (30 LS, 48 sporadic), and endometrial controls (29 LS, 37 sporadic). A 3-MDM panel (LASS4, LRRC4, and PPP2R5C) classified LS-CRC from LS controls with an AUC of 0.92 (0.84-0.99); results were similar for sporadic colorectal cancer. A 6-MDM panel (SFMBT2, MPZ, CYTH2, DIDO1, chr10.4479, and EMX2OS) discriminated LS-EC from LS controls with an AUC of 0.92 (0.83-1.0); the AUC for sporadic endometrial cancer versus sporadic controls was nominally higher, 0.99 (0.96-1.0).MDMs previously identified in sporadic endometrial cancer and colorectal cancer discriminate between endometrial cancer and benign endometrium and colorectal cancer and benign colorectum in LS. This supports the inclusion of patients with LS within future prospective clinical trials evaluating endometrial cancer and colorectal cancer MDMs and may provide a new avenue for cancer screening or surveillance in this high-risk population. PREVENTION RELEVANCE: Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgery. Methylated DNA markers previously identified in sporadic endometrial cancer and colorectal cancer discriminate between benign and cancer tissue in LS.

Unlocking High-Efficiency Methane Oxidation with Bimetallic Pd-Ce Catalysts under Zeolite Confinement.

Catalytic complete oxidation is an efficient approach to reducing methane emissions, a significant contributor to global warming. This approach requires active catalysts that are highly resistant to sintering and water vapor. In this work, we demonstrate that Pd nanoparticles confined within silicalite-1 zeolites (Pd@S-1), fabricated using a facile in situ encapsulation strategy, are highly active and stable in catalyzing methane oxidation and are superior to those supported on the S-1 surface due to a confinement effect. The activity of the confined Pd catalysts was further improved by co-confining a suitable amount of Ce within the S-1 zeolite (PdCe0.4@S-1), which is attributed to confinement-reinforced Pd-Ce interactions that promote the formation of oxygen vacancies and highly reactive oxygen species. Furthermore, the introduction of Ce improves the hydrophobicity of the S-1 zeolite and, by forming Pd-Ce mixed oxides, inhibits the transformation of the active PdO phase to inactive Pd(OH)2 species. Overall, the bimetallic PdCe0.4@S-1 catalyst delivers exceptional outstanding activity and durability in complete methane oxidation, even in the presence of water vapor. This study may provide new prospects for the rational design of high-performance and durable Pd catalysts for complete methane oxidation.

Smooth Muscle Tumors of the Uterus at MRI: Focus on Leiomyomas and FIGO Classification.

Leiomyomas are smooth muscle tumors of the uterus and are the most common uterine neoplasm. Although leiomyomas are usually asymptomatic, they can manifest with symptoms such as pain or uterine bleeding. Leiomyomas are classified on the basis of their anatomic location and morphology. Localization of leiomyomas relative to the endometrium, myometrium, and uterine serosa with use of the International Federation of Gynecology and Obstetrics (FIGO) classification system is helpful for guiding management in symptomatic patients. The FIGO system is a practical and universally accepted approach for classifying leiomyomas to guide radiologists and clinicians in deciding management. The MRI appearance of conventional leiomyomas is related to their tissue contents of smooth muscle and fibrous tissue and is well established. The MRI features of some leiomyoma subtypes and forms of degeneration also have been described. Other smooth muscle tumors of the uterus recognized in the 2020 World Health Organization classification system include intravenous leiomyomatosis, smooth muscle tumors of uncertain malignant potential, and metastasizing leiomyoma. At the far end of the spectrum are leiomyosarcomas, which are frankly malignant and therefore must be managed accordingly. Although MRI features that suggest a diagnosis of leiomyosarcoma have been proposed, these features overlap with those of some leiomyoma subtypes and degeneration. © RSNA, 2023 See the invited commentary by Fennessy and Gargiulo in this issue. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

Improving the process of ordering outside genomic testing for lung cancer FNA and small biopsy specimens - A multidisciplinary quality improvement project.

Objectives: Lung cancer is an important cause of mortality in the United States. Targeted mutation analysis has the potential to alter mortality in those with non-small-cell lung cancer. As such, the importance of timely tissue turnaround time (TAT) is substantial. We evaluated TAT at Mayo Clinic Arizona and found it to be delayed relative to national standards. Material and Methods: We conducted a series of plan, do, study, and act (PDSA) cycles at a single institution to identify areas for improvement with our lung cancer genomic testing. We assembled a multidisciplinary team and held serial meetings to discuss data from each PDSA cycle. Results: Using PDSA cycles and multidisciplinary discussions, we were able to identify a number of process limitations slowing TAT. We were then able to generate enhanced and timely communication between providers and pathology, educate and enforce the order/requisition workflow, and establish pathology accessioning with lung cancer specimens top priority. Conclusion: We were able to generate and implement a standard operating procedure for genomic testing of lung cancer specimens at our institution, thereby reducing tissue TAT.

Electrospun Ce-Mn oxide as an efficient catalyst for soot combustion: Ce-Mn synergy, soot-catalyst contact, and catalytic oxidation mechanism.

Increasing the contact efficiency and improving the intrinsic activity are two effective strategies to obtain efficient catalysts for soot combustion. Herein, the electrospinning method is used to synthesize fiber-like Ce-Mn oxide with a strong synergistic effect. The slow combustion of PVP in precursors and highly soluble manganese acetate in spinning solution facilitates the formation of fibrous Ce-Mn oxides. The fluid simulation clearly indicates that the slender and uniform fibers provide more interwoven macropores to capture soot particles than the cubes and spheres do. Accordingly, electrospun Ce-Mn oxide exhibits better catalytic activity than reference catalysts, including Ce-Mn oxides by co-precipitation and sol-gel methods. The characterizations suggest that Mn3+ substitution into fluorite-type CeO2 enhances the reducibility through the acceleration of Mn-Ce electron transfer, improves the lattice oxygen mobility by weakening the Ce-O bonds, and induces oxygen vacancies for the activation of O2. The theoretical calculation reveals that the release of lattice oxygen becomes easy because of a low formation energy of oxygen vacancy, while the high reduction potential is beneficial for the activation of O2 on Ce3+-Ov (oxygen vacancies). Due to above Ce-Mn synergy, the CeMnOx-ES shows more active oxygen species and higher oxygen storage capacity than CeO2-ES and MnOx-ES. The theoretical calculation and experimental results suggest that the adsorbed O2 is more active than lattice oxygen and the catalytic oxidation mainly follows the Langmuir-Hinshelwood mechanism. This study indicates that electrospinning is a novel method to obtain efficient Ce-Mn oxide.

Surface adsorbed and lattice oxygen activated by the CeO2/Co3O4 interface for enhancive catalytic soot combustion: Experimental and theoretical investigations.

Metal oxide-oxide interface on supported catalyst has been rarely studied due to the complex interfacial structure and synthetic challenge. Herein, different Ag-supported CeO2/Co3O4 samples with various covered-state of CeO2 were prepared for catalytic soot oxidation. In comparison, catalytic activity was significantly improved by grafting CeO2 on Co3O4, in which the best performing Ag/CoCe-2 exhibited remarkable catalytic performance towards soot oxidation with a T50 of 290.5 â„ƒ under 10 % O2/N2. Catalyst characterization investigated by Scanning Electron Microscope (SEM), quasi in-situ X-ray Photoelectron Spectroscopy (XPS), in-situ Raman, etc. revealed that this outstanding promotion in catalytic activity can be principally ascribed to the formation of the CeO2/Co3O4 interface. An appropriate CeO2 dosage maximized the contact and interaction between Co3O4 and CeO2, resulting in the largest CeO2/Co3O4 interface featured with abundant generated superoxide species and activated surface lattice oxygen. Density functional theory (DFT) calculations were also carried out for the oxygen vacancy formation energy, Gibbs free energy, etc. In presence of the CeO2/Co3O4 interface, a charge density redistribution around the adsorbed reactants at oxygen vacancies could be formed, owing to the efficient charge transfer enhanced by the electron-appealing effect. The change in electronic structure favored reducing the oxygen vacancy formation energy and boosting the lattice oxygen activation induced by the hybridized Co-O-Ce bonds, finally lowering the adsorption and activation barriers for reactive species and accelerating the reaction kinetics.

A Swollen Supraglottis.

A woman in her late 20s presented with difficulty phonating and singing for the past 15 months and no improvement from prior treatment with steroids and antibiotics for chronic laryngitis. What is your diagnosis?

Extraskeletal Ewing Sarcoma from Head to Toe: Multimodality Imaging Review.

Extraskeletal Ewing sarcoma (EES) is a rare subtype in the Ewing sarcoma family of tumors (ESFT), which also includes Ewing sarcoma of bone (ESB) and, more recently, primitive neuroectodermal tumors. Although these tumors often have different manifestations, they are grouped on the basis of common genetic translocation and diagnosis from specific molecular and immunohistochemical features. While the large majority of ESFT cases occur in children and in bones, approximately 25% originate outside the skeleton as EES. Importantly, in the adult population these extraskeletal tumors are more common than ESB. Imaging findings of EES tumors are generally nonspecific, with some variation based on location and the tissues involved. A large tumor with central necrosis that does not cross the midline is typical. Despite often nonspecific findings, imaging plays an important role in the evaluation and management of ESFT, with MRI frequently the preferred imaging modality for primary tumor assessment and local staging. Chest CT and fluorine 18 fluorodeoxyglucose PET/CT are most sensitive for detecting lung and other distant or nodal metastases. Management often involves chemotherapy with local surgical excision, when possible. A multidisciplinary treatment approach should be used given the propensity for large tumor size and local invasion, which can make resection difficult. Despite limited data, outcomes are similar to those of other ESFT cases, with 5-year survival exceeding 80%. However, with metastatic disease, the long-term prognosis is poor. ©RSNA, 2022.

Cytomorphology of NUTM1-rearranged sarcoma involving pleural fluid.

We describe an exceedingly rare cytology case of a NUTM1-rearranged sarcoma involving pleural fluid. A 48-year-old female presented with progressive abdominal pain. Computed tomography (CT) scan of the abdomen revealed a 5.6 cm soft tissue mass in the right hemi-abdomen. Needle core biopsy of the mass showed a small round cell tumor. Extensive work-up including next generation sequencing (NGS) demonstrated a NUTM1:MXI1 rearranged sarcoma. The patient was first treated with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy. She responded initially and then progressed with multiple masses in the abdomen and pleural effusion. The cytology of the pleural effusion showed clusters and single small round blue cells. Some of them displayed rhabdoid morphology. Immunostains of NUT antibody on cell block demonstrated strong positivity of NUT. NUTM1-rearranged sarcoma is an emerging class of mesenchymal neoplasm and the cytomorphology of this neoplasm in liquid-based cytology (LBC) is yet to be described. We herein reported the first cytology case of NUTM1-rearranged sarcoma in pleural fluid.

Porous stainless-steel fibers supported CuCeFeOx/Zeolite catalysts for the enhanced CO oxidation: Experimental and kinetic studies.

To develop novel catalysts of high-performance and cost-effectiveness, and to investigate the reaction kinetics of CO oxidation, ternary CuCeFeOx catalysts supported on zeolite/PSF (porous stainless-steel fibers) were synthesized for the first time. Effects of different Ce/Fe ratios, loading amounts, calcination temperatures, and reaction kinetics were investigated. Remarkably improved catalytic performance was achieved in the PSF-supported catalysts compared to the granular ones, owing to the increased mass/heat transfer efficiency and the high dispersion of active metal oxide species anchored on the zeolite layer. The Cu3Ce12Fe4-400 sample exhibited the best catalytic activity with a temperature difference in T90 of almost 40 °C lower than the worst one. Characterization results from XRD, FTIR, TEM, XPS, H2-TPR, etc. revealed that the promoted reducibility of metal oxides and formation of more oxygen vacancies significantly contributed to the enhanced catalytic activity. Furthermore, a generalized rate expression was derived from intrinsic and macro kinetic studies by assuming the conversion of CO to CO2 as the rate-determining step, in which CO oxidation over the PSF-supported catalysts followed the pseudo-first-order kinetic established by the Langmuir-Hinshelwood type mechanism.

Insight into the Improvement Effect of Nitrogen Dopant in Ag/Co3O4 Nanocubes for Soot Oxidation: Experimental and Theoretical Studies.

Different doping amounts of N-doped Ag/Co3O4 nanocubes were synthesized for the first time for catalytic soot oxidation. The N-doped sample exhibited remarkably improved catalytic activity, of which the maximum decrease in temperature for 90% soot conversion was almost 40 â„ƒ. Characterization results analyzed by TEM, XPS, EPR, H2-TPR, O2-TPD, etc. revealed that the incorporation of N atoms can alter the electronic structure, leading to the generation of more oxygen vacancies and enhancement of lattice oxygen mobility. Meanwhile, larger surface area, rugged morphology and promoted reducibility also contribute to the performance improvement. DFT calculations on the differential charge density, Gibbs free energy, etc. were performed to investigate the intrinsic reasons on an atomic level. Due to the relatively higher electronegativity, N dopant could be an electron-appealing center to promote efficient electron transfer, resulting in the redistribution of charge density and formation of conductive Co-N bonds. This variation in electronic structure favors lowering the formation energy of oxygen vacancies and facilitating the activation of the lattice oxygen originated from the highly hybridized Co-O bonds, which ultimately reduces the activation barriers for reactants/intermediates and accelerates the reaction kinetics. This study evidenced that N doping could be an effective strategy to promote catalytic soot oxidation.

Insight into the effect of manganese substitution on mesoporous hollow spinel cobalt oxides for catalytic oxidation of toluene.

The cobalt oxides and manganese oxides have high-activity potential for catalytic oxidation of volatile organic compounds (VOCs), while the mesoporous hollow morphology is crucial to the mass transfer of reactant and product. Therefore, it is worth investigating the effect of manganese substitution in mesoporous hollow cobalt oxides on catalytic oxidation. Herein, a partially disordered spinel structure is formed by the Mn substitution in Co3O4 and the mesoporous hollow microsphere is improved in morphology homogeneity with the decrease of Co/Mn ratio in the range of 1.8-28.8. The 5Co1Mn (Mn-substituted Co3O4 with Co/Mn at 5.4) exhibits outstanding catalytic activity for toluene oxidation with 50% CO2 generation at 237 °C, which is 21 °C lower than Co3O4. Moreover, the 5Co1Mn displays satisfactory stability in reusability, lifetime, and water resistance. The small defective crystallite, mesoporous hollow morphology, and high specific surface area endow Mn-substituted Co3O4 with more surface chemical adsorbed oxygen, enhancing the catalytic oxidation of toluene. Theoretical calculation on (311) plane of Co3O4 reveals that Mn2+ or Mn3+ substitution increases the formation energy of oxygen vacancy and makes it difficult to adsorb gaseous oxygen on the defective surface. The interaction between Co and Mn impedes the improvement of toluene oxidation because the mobility of lattice oxygen, the surface distribution of Co3+, and the ratio of surface adsorbed oxygen to surface lattice oxygen are hindered by Mn substitution. The chemical adsorbed oxygen is more active than lattice oxygen in the oxidation of adsorbed intermediates (phenolate, benzoate species, etc.). The Langmuir-Hinshelwood mechanism dominates in the catalytic oxidation at 200-250 °C, while the catalytic oxidation follows both the Langmuir-Hinshelwood mechanism and Mars-van Krevelen mechanism above 250 °C. This work provides some enlightenment for exploring the role of surface oxygen species in VOCs oxidation and uncovering the interaction in binary spinel oxides.

Chemisorbed Superoxide Species Enhanced the High Catalytic Performance of Ag/Co3O4 Nanocubes for Soot Oxidation.

The respective action mode between surface-adsorbed oxygen and bulk lattice oxygen during catalytic soot oxidation is still not fully recognized. Herein, a series of Ag-loaded Co3O4 catalysts with different Ag loading amounts were prepared by the impregnation method, and 5% Ag/Co3O4 presented competitive catalytic activity toward soot combustion with a T50 below 290 °C in 10% O2/N2. This remarkable improvement in catalytic performance could be primarily attributed to the enhanced Ag-Co3O4 metal-support interaction induced by the formation of uniform, dispersive, and suitable size metallic Ag nanoparticles. The activation, activity, consumption-regeneration, identification, and reaction of surface-adsorbed oxygen along with the activity of bulk lattice oxygen were characterized by various designed and in situ techniques. The results demonstrated that the chemisorbed superoxide species (O2-) play the potentially responsible role for boosting soot combustion, while the bulk lattice oxygen is much less active within the tested temperatures, inducing a negligible activity contribution. Moreover, soot-temperature programmed reduction, isothermal kinetic study, and density functional theory calculation provided supplementary support for the enhancement effect of Ag-Co3O4 combination in the activation and utilization of surface-adsorbed oxygen. The overall objective of this work is to identify the role of surface-adsorbed oxygen and bulk lattice oxygen for soot oxidation over Ag/Co3O4 catalysts.

Oncogenic gene transcripts detection by FISH on liquid-based cytology slides of 338 advanced lung cancer patients.

INTRODUCTION: Oncogenic gene transcripts in advanced lung cancer are a strong indication for targeted therapy. Cytology specimens are often the only materials available for oncogenic fusion analysis. This prospective study is to evaluate the feasibility of anaplastic lymphoma kinase (ALK) gene rearrangements, ROS oncogene 1 (ROS-1), and c-mesenchymal-epidermal transformation (c-MET) detected by fluorescence in situ hybridization (FISH) using liquid-based cytology (LBC) slides. MATERIALS AND METHODS: Consecutive cytology specimens including fine-needle aspiration biopsy (FNAB) and serous effusions from 338 advanced lung cancer patients were collected between March 1, 2015, and July 6, 2016. The correlation between ALK, ROS-1, c-MET, and other common driver gene abnormalities and the therapeutic response to crizotinib in ALK-positive patients were also evaluated. RESULTS: ALK fusion transcripts were detected in 31 of 338 patients (9.17%). Twenty-two of the 31 ALK-positive patients were treated with crizotinib at our institution (2 were lost to follow-up), and the overall response rate was 75.0 % (15 of 20); disease control rate was 90.0% (18 of 20). FISH analyses for ROS-1 and c-MET were performed on 75 and 73 patients, respectively, and showed 3 patients positive for ROS-1 and 3 positive for c-MET. These positive cases were all ALK-negative. CONCLUSION: For patients with advanced lung cancer, LBC slides are suitable for detecting oncogenic gene transcripts, and the results can provide a reliable guideline for targeted therapy.