Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease-Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

The pathogenesis of neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) in the gastrointestinal tract remains poorly understood. This study seeks to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared to a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation. Both groups exhibited a male predominance and similar age distribution. The NEC/MiNEN group was more likely to have a higher percentage of Crohn's disease (9/18 vs. 1/12, P=0.024), occur in the rectum (9/18 vs. 3/12) and small intestine (4/18 vs. 0/12) (P<0.01), be diagnosed on resection without a preceding biopsy (6/18 vs. 0/12, P=0.057), and have unidentifiable precursor lesions (10/18 vs. 1/12, P=0.018) than the control group. Synchronous carcinoma, advanced tumor stage (pT3 and pT4), and lymph node metastasis occurred at similar rates; however, the NEC/MiNEN group had a higher incidence of angiovascular invasion (14/18 vs. 4/12, P=0.024), distant metastasis (8/18 vs. 1/12, P=0.049), mortality (8/18 vs. 2/12, P=0.058), and worse survival (Kaplan-Meier, P=0.023) than the control group. All tested cases were mismatch repair proficient. A Ki-67 proliferation index ranged from 25% to 100%. Next-generation sequencing in 11 NEC/MiNEN cases revealed low tumor mutational burdens but complex genetic abnormalities commonly involving TP53 (9/11, 82%), FBXW7 (4/11, 36%), and APC (3/11, 27%), with the other genetic alterations randomly occurring in one or two cases. The neuroendocrine component, which shared similar molecular alterations as the non-neuroendocrine component, was subcategorized into intermediate (G3a)- and high-grade (G3b); the higher-grade correlated with more genetic alterations. In conclusion, IBD-associated NEC/MiNEN shows diverse histologic features, variable precursor lesions, intricate genetic abnormalities, and aggressive biologic behavior. The classification and grading of GI-NEC/MiNEN may be refined for better clinical management.

Clinically amyopathic dermatomyositis: Clinical, laboratory, and histopathological features.

BACKGROUND: Despite the advancements in the categorization of clinically amyopathic dermatomyositis (CADM), the classification and diagnosis of its subtypes are still challenging. The aim of our study was to describe the clinicopathological features of CADM and assess the differences between amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). METHODS: This retrospective study included 43 patients with CADM diagnosed at our institution from 2016 to 2020. Patients were subclassed into ADM (n = 30) and HDM (n = 13) groups to assess their clinicopathological differences. RESULTS: All included patients had characteristic cutaneous manifestations of dermatomyositis; 67.4% had myositis-associated auto-antibodies, including ANA (32.6%), RNP (14.0%), anti-Ro52 (9.3%), anti-p155/140 (7.0%), rheumatoid factor (7.0%), anti-NXP-2 (4.7%), anti-MDA5 (2.3%), and anti-Jo-1 (2.3%) antibodies. One patient had associated interstitial lung disease, and another patient had oral squamous cell carcinoma. The histopathological findings included mucin deposition (69.8%), telangiectasia (65.1%), lymphocytic infiltrate (48.8%), vacuolar interface dermatitis (46.5%), and epidermal atrophy (14.0%). Compared to patients with HDM, ADM patients were significantly less likely to have epidermal atrophy, 3.3% versus 38.5% (p = 0.006), and more likely to have mucin deposition, 80.0% versus 46.2% (p = 0.028). CONCLUSION: We described the clinicopathological features of CADM and highlighted the distinctions between ADM and HDM dermatopathologic findings. This information may prove helpful in diagnosing ambiguous lesions.

Effector Protein Serine Carboxypeptidase FgSCP Is Essential for Full Virulence in F. graminearum and Is Involved in Modulating Plant Immune Responses.

Fusarium head blight (FHB) caused by Fusarium graminearum is a significant pathogen affecting wheat crops. During the infection process, effector proteins are secreted to modulate plant immunity and promote infection. The toxin deoxynivalenol (DON) is produced in infected wheat grains, posing a threat to human and animal health. Serine carboxypeptidases (SCPs) belong to the α/ß hydrolase family of proteases and are widely distributed in plant and fungal vacuoles as well as animal lysosomes. Research on SCPs mainly focuses on the isolation, purification of a small number of fungi as well as their study in plants.However, their functions in F. graminearum, a fungal pathogen, remain relatively unknown. In this study, the biological functions of the FgSCP gene in F. graminearum were investigated. The study revealed that mutations in FgSCP affected nutritional growth, sexual reproduction, and stress tolerance of F. graminearum. Furthermore, the deletion of FgSCP resulted in reduced pathogenicity and hindered the biosynthesis of DON. The upregulation of FgSCP expression three days after infection indicated its involvement in host invasion, possibly acting as a "smokescreen" to deceive the host and suppress the expression of host defensive genes. Subsequently, we confirmed the secretion ability of FgSCP and its ability to inhibit the cell death induced by INF1 in Nicotiana. benthamiana cells, indicating its potential role as an effector protein in suppressing plant immune responses and promoting infection. In summary, we have identified FgSCP as an essential effector protein in F. graminearum, playing critical roles in growth, virulence, secondary metabolism, and host invasion.

METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2.

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether N6-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-d-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment.

Differential protein analysis of saline-alkali promoting the oil accumulation in Nitzschia palea.

BACKGROUND: The increasingly severe salinization of the aquatic environment has led to serious damage to the habitats of aquatic organisms. Benthic diatoms are commonly employed as indicator species for assessing water quality and serve as a reflection of the overall health of the aquatic ecosystem. Nitzschia palea is a common diatom found in freshwater, with high oil content, rapid reproductive rate, and it is a commonly dominant species in various rivers. RESULTS: The results showed that after 4 days (d) of saline-alkali stress, the cell density and chlorophyll a content of Nitzschia palea reached their maximum values. Therefore, we selected Nitzschia palea under 4 d stress for Tandem Mass Tag (TMT) quantitative proteomic analysis to explore the molecular adaptation mechanism of freshwater diatoms under saline-alkali stress. Totally, 854 proteins were enriched, of which 439 differentially expressed proteins were identified. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and subcellular fractionation analysis revealed that these proteins were mainly enriched in the photosynthesis pathway, citric acid cycle (TCA cycle), fatty acid synthesis, and glutathione cycle. CONCLUSIONS: This study aims to reveal the physiological, biochemical and proteomic mechanisms of salt and alkali tolerance and molecular adaptation of Nitzschia palea under different saline-alkali concentrations. This study showed that Nitzschia palea is one candidate of the environmental friendly, renewable bioenergy microalgae. Meantime, Nitzschia palea reveals for the proteome of the freshwater and provides the basis, it became a model algal species for freshwater diatoms.

Protein Disulfide Isomerase FgEps1 Is a Secreted Virulence Factor in Fusarium graminearum.

Protein disulfide isomerase (PDI) is a member of the thioredoxin (Trx) superfamily with important functions in cellular stability, ion uptake, and cellular differentiation. While PDI has been extensively studied in humans and animals, its role in fungi remains relatively unknown. In this study, the biological functions of FgEps1, a disulfide bond isomerase in the fungal pathogen Fusarium graminearum, were investigated. It was found that FgEps1 mutation affected nutritional growth, asexual and sexual reproduction, and stress tolerance. Additionally, its deletion resulted in reduced pathogenicity and impaired DON toxin biosynthesis. The involvement of FgEps1 in host infection was also confirmed, as its expression was detected during the infection period. Further investigation using a yeast signal peptide secretion system and transient expression in Nicotiana benthamiana showed that FgEps1 suppressed the immune response of plants and promoted infection. These findings suggest that virulence factor FgEps1 plays a crucial role in growth, development, virulence, secondary metabolism, and host infection in F. graminearum.

Exploring the Effectiveness of Natural Food Flavors in Protecting Carbon Steel against CO2-Induced Corrosion.

Two food flavors, furfuryl mercaptan (2-FFT) and difurfuryl disulfide (DFDS), were investigated as green corrosion inhibitors for the N80 steel in a CO2-saturated solution containing 3.5% NaCl. Experimental methods, quantum chemical calculations, and molecular dynamics simulation were employed to evaluate the effectiveness of 2-FFT and DFDS. The results of the study indicate that both 2-FFT and DFDS act as mixed corrosion inhibitors, with a dominant inhibition effect on the cathodic reaction. 2-FFT is physiochemically adsorbed on the steel surface in a tiled form through the furan ring and the - SH groups as adsorption sites. On the other hand, DFDS is chemisorbed on the steel surface through the - S-S- groups in a parallel manner. DFDS exhibits a higher tendency for electron transfer and stronger adsorption to steel compared to 2-FFT. Overall, this study highlights the potential of natural food flavors as effective and environmentally friendly corrosion inhibitors for carbon steel in CO2-saturated environments. The findings of this research can contribute to the development of sustainable and nontoxic corrosion inhibitors for the oil and gas industry.

Identification of MKI67, TPR , and TCHH Mutations as Prognostic Biomarkers for Patients With Defective Mismatch Repair Colon Cancer Stage II/III.

BACKGROUND: Stage II/III disease is the most predominant form of colorectal cancer, accounting for approximately 70% of cases. Furthermore, approximately 15% to 20% of patients with stage II/III disease have deficient mismatch repair or microsatellite instability-high colorectal cancer. However, there are no identified significant prognostic biomarkers for this disease. OBJECTIVE: To identify prognostic markers for patients with deficient mismatch repair/microsatellite instability-high colon cancer stage II/III. DESIGN: Retrospective study design. SETTING: The study was conducted at a high-volume colorectal center, the Cancer Hospital, Chinese Academy of Medical Sciences. PATIENTS: Patients diagnosed with stage II/III deficient mismatch repair/microsatellite instability-high colon cancer who underwent curative surgery at the Cancer Hospital at the Chinese Academy of Medical Sciences between July 2015 and November 2018 were included. MAIN OUTCOME MEASURES: The primary outcome measure was the influence of differentially mutated genes on progression-free survival. RESULTS: The retrospective deficient mismatch repair/microsatellite instability-high cohort involved 32 patients and The Cancer Genome Atlas-microsatellite instability-high cohort involved 45 patients. Patients with deficient mismatch repair/microsatellite instability-high colon cancer had higher mutational frequencies of MKI67 , TPR , and TCHH than patients with microsatellite stable colon cancer. MKI67 , TPR , TCHH , and gene combination were significantly correlated with prognosis. The biomarker mutation-type colon cancer group had a higher risk of recurrence or death than did the wild-type group. Moreover, biomarker mutation-type tumors had more mutations in the DNA damage repair pathway and tumor mutational burden than did biomarker wild-type tumors. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: MKI67 , TPR , and TCHH may serve as potential diagnostic and prognostic biomarkers for deficient mismatch repair/microsatellite instability-high colon cancer stage II/III. IDENTIFICACIN DE MUTACIONES MKI, TPR Y TCHH COMO BIOMARCADORES PRONSTICOS PARA PACIENTES CON CNCER DE COLON EN ETAPA II/III CON DEFICIENCIA EN LA REPARACION DE ERRORES DE EMPAREJAMIENTO: ANTECEDENTES:La enfermedad en estadio II/III es la forma más predominante de cáncer colorrectal y representa aproximadamente el 70% de los casos. Además, aproximadamente entre el 15% y el 20% de los pacientes con enfermedad en estadio II/III tienen reparación deficiente de errores de emparejamiento o inestabilidad de microsatélital alta. Sin embargo, no se han identificado biomarcadores pronósticos significativos para esta enfermedad.OBJETIVO:Este estudio tuvo como objetivo identificar marcadores pronósticos para pacientes con cáncer de colon con reparación deficiente de errores de emparejamiento/inestabilidad microsatelital alta en estadio II/III.DISEÑO:Diseño de estudio retrospectivo.ESCENARIO:El estudio se realizó en un centro colorrectal de alto volumen, el Hospital del Cáncer de la Academia China de Ciencias Médicas.PACIENTES:Pacientes diagnosticados con cáncer de colon en estadio II/III con reparación deficiente de errores de emparejamiento o inestabilidad de microsatélital alta que se sometieron a cirugía curativa en el Hospital del Cáncer de la Academia China de Ciencias Médicas entre julio de 2015 y noviembre de 2018.MEDIDAS DE RESULTADO PRINCIPALES:La medida de resultado primaria fue la influencia de los genes con mutaciones diferenciales en la supervivencia libre de progresión.RESULTADOS:La cohorte retrospectiva de reparación deficiente de errores de emparejamiento o inestabilidad de microsatélital alta y la cohorte de inestabilidad microsatelital alta del Atlas del Genoma del Cáncer involucraron a 32 y 45 pacientes, respectivamente. Los pacientes con de reparación deficiente de errores de emparejamiento/inestabilidad microsatélital alta tuvieron frecuencias mutacionales más altas de MKI67 , TPR y TCHH que los pacientes estables de microsatélites. MKI67 , TPR , TCHH , y la combinación de genes se correlacionaron significativamente con el pronóstico. El grupo de cáncer de colon de tipo mutación de biomarcador tenía un mayor riesgo de recurrencia o muerte que el grupo de mutación salvaje. Además, los tumores de tipo mutación de biomarcadores tenían más mutaciones en la vía de reparación del daño del ADN y la carga mutacional del tumor que los tumores de tipo salvaje de biomarcadores.LIMITACIONES:Este estudio estuvo limitado por su naturaleza retrospectiva.CONCLUSIONES:MKI67 , TPR , y TCHH pueden servir como posibles biomarcadores de diagnóstico y pronóstico para cáncer de colon en estadio II/III con reparación deficiente de errores de emparejamiento/inestabilidad microsatélital alta. (Traducción-Dr. Jorge Silva Velazco ).

Identification of a Novel Walnut Iron Chelating Peptide with Potential High Antioxidant Activity and Analysis of Its Possible Binding Sites.

Peptide iron chelate is widely regarded as one of the best iron supplements for relieving iron deficiency. In this study, a new type of walnut peptide iron (WP-Fe) chelate was prepared using low molecular weight walnut peptides (WP) as raw materials. Under the conditions of this study, the chelation rate and iron content of the WP-Fe chelate were 71.87 ± 1.60% and 113.11 ± 2.52 mg/g, respectively. Fourier transform infrared spectroscopy (FTIR), zeta potential, amino acid composition, and other structural analysis showed that WP-Fe is formed by the combination of carboxyl, amino and carbonyl with Fe2+. The WP-Fe chelate exhibits a honeycomb-like bulk structure different from that of WP. In addition, we predicted and established the binding model of ferrous ion and WP by molecular docking technology. After chelation, the free radical scavenging ability of the WP-Fe chelate was significantly higher than that of the WP. Overall, the WP-Fe chelate has high iron-binding capacity and antioxidant activity. We believe that peptides from different sources also have better iron binding capacity, and peptide iron chelates are expected to become a promising source of iron supplement and antioxidant activities.

SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection.

We review research regarding the epidemiology, risk factors, genetic susceptibility, molecular pathology, and early detection of SCLC, a deadly tumor that accounts for 14% of lung cancers. We first summarize the changing incidences of SCLC globally and in the United States among males and females. We then review the established risk factor (i.e., tobacco smoking) and suspected nonsmoking-related risk factors for SCLC, and emphasize the importance of continued effort in tobacco control worldwide. Review of genetic susceptibility and molecular pathology suggests different molecular pathways in SCLC development compared with other types of lung cancer. Last, we comment on the limited utility of low-dose computed tomography screening in SCLC and on several promising blood-based molecular biomarkers as potential tools in SCLC early detection.

A safer and more practical tracheotomy in invasive mechanical ventilated patients with COVID-19: A quality improvement study.

Importance: The number of infections and deaths caused by the global epidemic of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) invasion is steadily increasing daily. In the early stages of outbreak, approximately 15%-20% of patients with coronavirus disease 2019 (COVID-19) inevitably developed severe and critically ill forms of the disease, especially elderly patients and those with several or serious comorbidities. These more severe forms of disease mainly manifest as dyspnea, reduced blood oxygen saturation, severe pneumonia, acute respiratory distress syndrome (ARDS), thus requiring prolonged advanced respiratory support, including high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), and invasive mechanical ventilation (IMV). Objective: This study aimed to propose a safer and more practical tracheotomy in invasive mechanical ventilated patients with COVID-19. Design: This is a single center quality improvement study. Participants: Tracheotomy is a necessary and important step in airway management for COVID-19 patients with prolonged endotracheal intubation, IMV, failed extubation, and ventilator dependence. Standardized third-level protection measures and bulky personal protective equipment (PPE) may hugely impede the implementation of tracheotomy, especially when determining the optimal pre-surgical positioning for COVID-19 patients with ambiguous surface position, obesity, short neck or limited neck extension, due to vision impairment, reduced tactile sensation and motility associated with PPE. Consequently, the aim of this study was to propose a safer and more practical tracheotomy, namely percutaneous dilated tracheotomy (PDT) with delayed endotracheal intubation withdrawal under the guidance of bedside ultrasonography without the conventional use of flexible fiberoptic bronchoscopy (FFB), which can accurately determine the optimal pre-surgical positioning, as well as avoid intraoperative damage of the posterior tracheal wall and prevent the occurrence of tracheoesophageal fistula (TEF).

Intermolecular hydrogen bonds between catechin and theanine in tea: slow release of the antioxidant capacity by a synergetic effect.

The health benefits of drinking tea stem from it being rich in polyphenols and other physiologically-active substances. Thus, exploring the synergistic effect between polyphenols and a variety of physiologically-active substances can contribute to our understanding of how tea benefits health. In this work, we have studied the interactions between catechin and theanine, exploring the synergetic antioxidant mechanism of the two molecules. Electrochemical characterization results showed that the oxidation peak current of catechin decreased gradually with the concentration of theanine, which is due to theanine spontaneously binding to catechin through intermolecular hydrogen bonds and forming molecular clusters via two hydrogen bonds. The binding constant is 4.75 at room temperature. The molecular clusters reduce the diffusion coefficient of catechin in solution, leading to the slow release of its antioxidant capacity (ability to effectively inhibit free radical oxidation reactions). Density functional theory calculations were also performed and verified the binding behavior. In identifying the synergistic effect between catechin and theanine on the antioxidant capacity of tea, this study adds to our understanding of the efficacy of tea polyphenols.

miR-152-3p Represses the Proliferation of the Thymic Epithelial Cells by Targeting Smad2.

MicroRNAs (miRNAs) control the proliferation of thymic epithelial cells (TECs) for thymic involution. Previous studies have shown that expression levels of miR-152-3p were significantly increased in the thymus and TECs during the involution of the mouse thymus. However, the possible function and potential molecular mechanism of miR-152-3p remains unclear. This study identified that the overexpression of miR-152-3p can inhibit, while the inhibition of miR-152-3p can promote, the proliferation of murine medullary thymic epithelial cell line 1 (MTEC1) cells. Moreover, miR-152-3p expression was quantitatively analyzed to negatively regulate Smad2, and the Smad2 gene was found to be a direct target of miR-152-3p, using the luciferase reporter assay. Importantly, silencing Smad2 was found to block the G1 phase of cells and inhibit the cell cycle, which was consistent with the overexpression of miR-152-3p. Furthermore, co-transfection studies of siRNA-Smad2 (siSmad2) and the miR-152-3p mimic further established that miR-152-3p inhibited the proliferation of MTEC1 cells by targeting Smad2 and reducing the expression of Smad2. Taken together, this study proved miR-152-3p to be an important molecule that regulates the proliferation of TECs and therefore provides a new reference for delaying thymus involution and thymus regeneration.

Primary hemangioblastoma of the kidney with molecular analyses by next generation sequencing: a case report and review of the literature.

BACKGROUND: Hemangioblastoma is an indolent mesenchymal tumor most frequently occurring in the central nervous system (CNS), but can also arise extraneuraxially, as part of Von Hippel-Lindau (VHL) disease or in sporadic tumors. Extraneuraxial hemangioblastomas occur outside the central nervous system. It includes tumors arising from the nervous paraneuraxial structures and visceral organs. Sporadic hemangioblastoma of the kidney, a rare subset of extraneuraxial hemangioblastomas, is an under-recognized renal neoplasm. There have been only 25 cases described to date in the English language literature. We report herein one additional sporadic tumor in a patient without VHL disease. CASE PRESENTATION: A 61 year old male presenting with gross hematuria was found to have a 3.5 cm renal mass at the lateral mid to lower pole of the left kidney on computed tomography urogram. The patient underwent a partial nephrectomy for the mass. Pathological examination showed a well-circumscribed non-encapsulated tumor composed of sheets of large polygonal cells traversed by a rich vascular network. The tumor cells showed clear to eosinophilic cytoplasm and overall bland nuclei. The diagnosis of hemangioblastoma was confirmed by positive immunostaining for alpha-inhibin, S100, neuron-specific enolase, and PAX8. No significant gene mutations, including VHL gene and copy number changes were detected in the tumor using next generation sequencing supporting the diagnosis of sporadic renal hemangioblastoma. CONCLUSION: Sporadic renal hemangioblastoma is a rare subset of extraneuraxial hemangioblastomas. We report one such tumor in a patient without clinical or molecular evidence of VHL disease. The literature was reviewed to better understand the clinical, radiological, pathological, and molecular features of this neoplasm. The majority of renal hemangioblastomas showed positive immunostaining for PAX8, which supports the idea that the immunoprofiles of extraneuraxial hemangioblastomas can vary depending on sites of origin. Diagnosis of renal hemangioblastoma is challenging because of its rarity and overlapping microscopic and immunophenotypic features with other renal tumors, including clear cell renal cell carcinoma. In some cases, molecular or genetic studies may be necessary to obtain an accurate diagnosis. Since renal hemangioblastoma is clinically benign, recognition of this pathological entity is important to avoid unnecessary over-treatment.

An accessible, efficient, and accurate natural language processing method for extracting diagnostic data from pathology reports.

Context: Analysis of diagnostic information in pathology reports for the purposes of clinical or translational research and quality assessment/control often requires manual data extraction, which can be laborious, time-consuming, and subject to mistakes. Objective: We sought to develop, employ, and evaluate a simple, dictionary- and rule-based natural language processing (NLP) algorithm for generating searchable information on various types of parameters from diverse surgical pathology reports. Design: Data were exported from the pathology laboratory information system (LIS) into extensible markup language (XML) documents, which were parsed by NLP-based Python code into desired data points and delivered to Excel spreadsheets. Accuracy and efficiency were compared to a manual data extraction method with concordance measured by Cohen's κ coefficient and corresponding P values. Results: The automated method was highly concordant (90%-100%, P<.001) with excellent inter-observer reliability (Cohen's κ: 0.86-1.0) compared to the manual method in 3 clinicopathological research scenarios, including squamous dysplasia presence and grade in anal biopsies, epithelial dysplasia grade and location in colonoscopic surveillance biopsies, and adenocarcinoma grade and amount in prostate core biopsies. Significantly, the automated method was 24-39 times faster and inherently contained links for each diagnosis to additional variables such as patient age, location, etc., which would require additional manual processing time. Conclusions: A simple, flexible, and scaleable NLP-based platform can be used to correctly, safely, and quickly extract and deliver linked data from pathology reports into searchable spreadsheets for clinical and research purposes.

Response to toripalimab combined with radiotherapy in advanced non-small cell lung cancer-not otherwise specified: A case report.

RATIONALE: The targeting of signal transduction through programmed cell death receptor-1 (PD-1) and its ligand programmed cell death-ligand 1 (PD-L1) in patients with non-small cell lung cancer (NSCLC) has been widely applied in clinical research. However, the subtypes and treatment patterns that predict responses to PD-1/PD-L1 inhibitors are not fully understood. Biomarkers, such as PD-L1 expression, tumor mutation load, and DNA mismatch repair defects, have been used to screen patients who respond to PD-1/PD-L1 inhibitors, but the appropriate treatment mode requires further investigation. Immune checkpoint inhibitors combined with radiotherapy provide benefits from remote effects, especially in NSCLC patients with increased PD-L1 expression. PATIENT CONCERNS: We report a 64-year-old man who presented with left back pain for 40 days. A computed tomography scan showed a mass in the right upper lobe of the lung, with metastases in the right hilar and mediastinal lymph nodes. DIAGNOSIS: NSCLC-not otherwise specified was diagnosed by computed tomography-guided lung biopsy. INTERVENTIONS: After the failure of first-line chemotherapy, next-generation sequencing was performed for comprehensive gene analysis, and PD-L1 expression levels were evaluated by immunohistochemistry. The patient was treated with toripalimab (a PD-1 inhibitor) concurrently with radiotherapy for bone metastases. OUTCOMES: The detection results showed a high tumor mutation burden and increased PD-L1 expression. On the basis of these findings, the patient received toripalimab (PD-1 inhibitor) combined with radiotherapy for bone metastases. Partial response was achieved after 3 cycles, and the patient showed stable disease at the end of the sixth and ninth cycles of toripalimab. The patient was followed up for 26 months. At present, the patient is receiving toripalimab maintenance treatment, which has been well-tolerated without adverse events. LESSON: Toripalimab combined with radiotherapy may exert a synergistic anti-tumor effect through remote effects in advanced or metastatic NSCLC with high PD-L1 expression. However, the specific treatment mode requires further confirmation by the investigation of additional cases.

Identification of a Novel Immune-Related CpG Methylation Signature to Predict Prognosis in Stage II/III Colorectal Cancer.

With the increasing incidence of colorectal cancer (CRC) and continued difficulty in treating it using immunotherapy, there is an urgent need to identify an effective immune-related biomarker associated with the survival and prognosis of patients with this disease. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of autoimmunity, aging, and cancer. In this study, we aimed to identify a novel immune-related methylated signature to aid in predicting the prognosis of patients with CRC. We investigated DNA methylation patterns in patients with stage II/III CRC using datasets from The cancer genome atlas (TCGA). Overall, 182 patients were randomly divided into training (n = 127) and test groups (n = 55). In the training group, five immune-related methylated CG sites (cg11621464, cg13565656, cg18976437, cg20505223, and cg20528583) were identified, and CG site-based risk scores were calculated using univariate Cox proportional hazards regression in patients with stage II/III CRC. Multivariate Cox regression analysis indicated that methylated signature was independent of other clinical parameters. The Kaplan-Meier analysis results showed that CG site-based risk scores could significantly help distinguish between high- and low-risk patients in both the training (P = 0.000296) and test groups (P = 0.022). The area under the receiver operating characteristic curve in the training and test groups were estimated to be 0.771 and 0.724, respectively, for prognosis prediction. Finally, stratified analysis results suggested the remarkable prognostic value of CG site-based risk scores in CRC subtypes. We identified five methylated CG sites that could be used as an efficient overall survival (OS)-related biomarker for stage II/III CRC patients.