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Human epidermal growth factor receptor‐2 (HER2), programmed death‐ligand 1 (PD‐L1), and microsatellite (MS) status are well‐established biomarkers in gastroesophageal adenocarcinomas (GEAs). However, it is unclear how the combination of these biomarkers is associated with clinicopathological factors and prognosis. This retrospective study included baseline metastatic GEA patients who were tested for all three biomarkers (HER2, PD‐L1, and MS status) at the MD Anderson Cancer Center between 2012 and 2022. Stratification was performed according to the combination of biomarker profiles: triple negative (TN), single positive (SP), and multiple positive (MP). Comparative analyses of clinicopathological factors and survival using combinations of biomarkers were performed. Among the 698 GEA patients analyzed, 251 (36.0%) were classified as TN, 334 (47.9%) as SP, and 113 (16.1%) as MP. The MP group showed a significant association with tumors located in the esophagus (p <.001), well to moderate differentiation (p <.001), and the absence of signet ring cells (p <.001). In the survival analysis, MP group had a significantly longer overall survival (OS) compared to the other groups (MP vs. TN, p <.001 and MP vs. SP, p <.001). Multivariate Cox regression analysis revealed that MP serves as an independent positive prognostic indicator for OS (hazard ratio = 0.63, p <.01). Our findings indicate that MP biomarkers are associated with a favorable prognosis in metastatic GEA. These results are reflective of clinical practice and offer valuable insights into how therapeutics and future biomarkers could influence therapy/prognosis. [ABSTRACT FROM AUTHOR]

Background: Trichorhinophalangeal syndrome 1 (TRPS1) expression in primary breast and other solid tumors has been investigated but its role as a marker in metastatic tumors is unclear. The objective of this study was to evaluate the sensitivity and specificity of TRPS1 as a breast cancer immunomarker in metastatic tumors that originated from breast, Müllerian, lung, gastrointestinal (GI), and pancreatic primary tumors with cell blocks from fine‐needle aspiration (FNA) and effusion specimens. Methods: Cell blocks were immunostained with anti‐TRPS1 monoclonal antibody (clone EPR16171). Histochemical scores (H scores) (proportion × intensity; range, 0–300) were assigned; H scores of ≥10 were considered positive. Overall, 160 specimens were examined, including 127 FNAs (35 breast, 25 Müllerian, 36 lung, and 31 GI and pancreatic carcinomas) and 33 effusion specimens (18 breast, 12 Müllerian, one lung, and two GI carcinomas). Results: TRPS1 was positive in 51 of 53 (96%) metastatic breast carcinomas and in 28 of 107 (26.2%) nonbreast metastatic tumors. Metastatic breast carcinoma showed the highest mean H score of 247.35, compared to 45.36 in Müllerian, 8.4 in lung, and 5.88 in GI tumors. The sensitivity and specificity of TRPS1 for identifying a breast origin in metastatic tumors was 96.22% and 72.89%, respectively. Conclusions: Despite high overall sensitivity, TRPS1 showed lower specificity as a breast immunomarker because of its expression in nonbreast tumors. The mean H score in nonbreast tumors was significantly lower than in metastatic breast tumors. It is important to recognize the broad range of expression of TRPS1 in metastatic breast and nonbreast tumors to avoid an incorrect determination of a metastatic tumor's organ of origin. Trichorhinophalangeal syndrome 1 (TRPS1) expression in metastatic tumors with cytology cell blocks showed high sensitivity but lower specificity for identifying an origin from primary breast cancer. The proportion and intensity of staining in nonbreast metastatic tumors were significantly lower than in metastatic breast tumors. It is important to recognize the broad range of TRPS1 expression in metastatic breast and nonbreast tumors and to use additional immunomarkers to avoid incorrectly identifying the organ of origin of a metastatic tumor. [ABSTRACT FROM AUTHOR]

As of July 30, 2020, the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 had resulted in more than 150 000 deaths in the [...], * Context.--As teaching hospitals institute social distancing and defer nonemergent procedures to cope with the coronavirus disease 2019 pandemic, the need for daily onsite presence, unless necessary, has been reduced for all medical staff, including trainees. Pathology training programs must adapt to these changes to ensure overall safety without significantly compromising training and the educational mission of the institution. Objective.--To describe the hybrid on-site and remote anatomic pathology training model in response to the coronavirus disease 2019 pandemic that was implemented in our pathology department and report the clinical fellows&apos; responses to the survey about their experiences. Design.--The hybrid model was implemented March 25, 2020. Fellows alternate weekly between working on site and working remotely. On site, fellows wear personal protective equipment and maintain social distancing. Remotely, fellows use digital pathology to review cases and supplement with online educational activities. Virtual "coffee breaks," meditation, and exercise are part of the curriculum. Online platforms, including WebEx, Google Classroom, and Canvas, are used to continue educational activities. The survey was open May 19 through June 8, 2020. Results.--Twenty-eight of the 29 clinical fellows (96%) responded. Many of the respondents indicated substantial increase in their skill with using digital pathology and online platforms during the pandemic. The top most helpful resources were the United States and Canadian Academy of Pathology interactive microscopy courses (found very or somewhat helpful by 22 of 23 clinical fellows; 96%), ExpertPath (19 of 23; 82%), the College of American Pathologists virtual learning series (18 of 23; 78%), the World Health Organization Blue Books (16 of 23; 70%), the American Society of Cytopathology webinars (14 of 23; 61%), and our institutional digital slide collection (12 of 23; 52%). Conclusions.--Hybrid on-site and remote training can maximize anatomic pathology learning opportunities while maintaining the safety of trainees, hospital personnel, and the community. (Arch Pathol Lab Med. 2021;145:22-31; doi: 10.5858/arpa.2020-0467-SA)

Agricultural insurance is instrumental in consolidating the gains of poverty alleviation and advancing rural revitalization. It significantly aids in the efficient allocation of agricultural production factors, which in turn enhances agricultural output and bolsters the evolution of modern agriculture. Therefore, utilizing data from 583 household surveys and employing endogenous transformation and intermediary effect models, this paper analyzes the production factor allocation effect and specific mechanism of agricultural insurance. It focuses on small-scale farmers and new agricultural operators, exploring how insurance contributes to the advancement of modern agricultural practices. The results show the following: (1) Agriculture insurance can significantly affect the agricultural scale input behavior of farmers such as land input scale and input scale, agricultural machinery application behavior such as the degree of mechanization and water conservancy application, agricultural technology adoption behavior, and planting structure selection behavior, thereby helping to modernize agriculture. (2) There is heterogeneity in the impact of agriculture insurance on the allocation of production factors for small farmers and new agricultural operators. For small farmers, agriculture insurance has a significant promoting effect on their agricultural machinery application behavior, agricultural technology adoption behavior, and planting structure selection behavior. For new agricultural operators, agriculture insurance significantly promotes their agricultural scale input behavior, agricultural machinery application behavior, and agricultural technology adoption behavior. (3) In terms of the mechanism of action, agriculture insurance mainly promotes agricultural scale input behavior through land transfer, facilitates agricultural machinery application behavior by purchasing agricultural machinery equipment and services, encourages agricultural technology adoption behavior by strengthening agricultural technology training, and enhances professional production levels by increasing the scale of insured planting, thereby contributing to the development of modern agriculture. Based on this, several policy suggestions have been proposed. These include enhancing the directionality of agriculture insurance policies, improving the collaborative interaction mechanism between agriculture insurance and agricultural credit financing, and adopting certain reward and punishment measures to curb moral hazard. [ABSTRACT FROM AUTHOR]

Positron emission tomography with computed tomography (PET-CT) is an integral test in the staging of lung cancer, evaluating both intrathoracic lymph nodes and distant metastasis. (1) Although it has high [...], * Context.--Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is routinely used to evaluate mediastinal lymph nodes (LNs), especially for cancer staging. There are limited large studies evaluating the cytologic, radiologic, and clinical features of [sup.18]F-fluorodeoxy glucose positron emission tomography-computed tomography-positive (PET-CT+) LNs. Objective.--To compare cytologic, radiologic, and clinical features of PET-CT+, cytology-malignant (PET-CT+/Cyto+) and PET-CT+, cytology-benign (PET-CT+/Cyto-) LNs. Design.--The pathology database was searched for cases of mediastinal LNs obtained by EBUS-TBNA from January 1, 2015 to December 31, 2015. The cytologic, radiologic, and clinical features were collected for all PET-CT+ LNs. Results.--Of 2267 mediastinal LNs obtained by EBUSTBNA during this period, 577 LNs met the criteria. Of the latter, 263 (46%) were PET-CT+/Cyto+ and 314 (54%) were PET-CT+/Cyto-. All of the patients with PET-CT+/Cyto+ results had a prior or concurrent diagnosis of malignancy as compared to 89% of patients with PETCT+/Cyto-results. Of the 224 patients with PET-CT+/Cyto+ LNs, 177 (79%) had metastases from lung primary, 43 (19%) had metastases from nonlung primaries, and 7 (3%) had lymphoma. Average LN size was larger in the PET-CT+/Cyto+ group than in the PET-CT+/Cyto-group (14.6 mm versus 9.58 mm), and mean standardized uptake value in PET-CT+/Cyto+ LNs was higher than that of PET-CT+/Cyto-LNs (10.05 versus 5.99). Significant cytologic findings in PET-CT+/Cyto-cases were necrosis and granulomatous inflammation, including 3 cases with fungal organisms. Conclusions.--PET-CT positivity alone was nonspecific for malignancy and insufficient to guide management of patients with mediastinal adenopathy, but specificity could be improved when combined with LN size and standardized uptake value. (Arch Pathol Lab Med. 2019;143:1265-1270; doi: 10.5858/arpa.2018-0483-OA)

The primary goal of Chinese agricultural development is to guarantee national food security and supply of major agricultural products. Hence, the scientific work on agricultural monitoring and early warning as well as agricultural outlook must be strengthened. In this study, we develop the China Agricultural Monitoring and Early-warning System (CAMES) on the basis of a comparative study of domestic and international agricultural outlook models. The system is a dynamic and multi-market partial equilibrium model that integrates biological mechanisms with economic mechanisms. This system, which includes 11 categories of 953 kinds of agricultural products, could dynamically project agricultural market supply and demand, assess food security, and conduct scenario analysis at different spatial levels, time scale levels, and macro-micro levels. Based on the CAMES, the production, consumption, and trade of the major agricultural products in China over the next decade are projected. The following conclusions are drawn: i) The production of major agricultural products will continue to grow steadily, mainly because of the increase in yield. ii) The growth of agricultural consumption will be slightly higher than that of agricultural production. Meanwhile, a high self-sufficiency rate is expected for cereals such as rice, wheat, and maize, with the rate being stable at around 97%. iii) Agricultural trade will continue to thrive. The growth of soybean and milk imports will slow down, but the growth of traditional agricultural exports such as vegetables and fruits is expected to continue.

Objectives When desmoplastic small round cell tumor (DSRCT) is present in serous fluid, the cytomorphology can be diverse and can mimic metastatic carcinomas and thus present a diagnostic challenge. The aim of this study was to evaluate the cytomorphologic and immunocytochemical features of this rare tumor in serous effusion specimens. Methods Demographic, clinical, radiologic, and pathologic information from patients who had a DSRCT diagnosis on body fluid specimens was collected and cytologic slides were reviewed. Results Nine specimens were identified (5 pleural fluid and 4 ascitic fluid specimens) from 8 patients (5 male and 3 female). The mean patient age at diagnosis was 26 years. The most common symptoms were abdominal distension and pain, with 5 patients having abdominal masses. Other findings included peritoneal carcinomatosis, liver masses, ascites, and pleural nodules. The predominant cytomorphology was loose cellular clusters, followed by tight clusters of small cells with scant occasional vacuolated cytoplasm and a sphere-like pattern. Conclusions Serous fluid may be the first available specimen to diagnose DSRCT. In young patients with no history of malignancy and radiologic finding of peritoneal implants, DSRCT should be considered a possibility in the differential diagnosis, and sensitive markers should be used for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background: Claudin‐4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin‐4 versus MOC‐31 and Ber‐EP4 by comparing their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens. Methods: This retrospective study comprised a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine‐needle aspiration specimens. Cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign. Cell block sections were stained for claudin‐4 and compared with those previously stained for MOC‐31 and Ber‐EP4. Indefinite cases were further reclassified based on clinical and pathologic findings into benign (26 cases), mesothelioma (11 cases), and carcinoma (nine cases). Results: None of the mesotheliomas (0/39) or benign effusions (0/47) were positive for claudin‐4, whereas 134 of the 143 carcinoma specimens were positive. Compared to MOC‐31 and Ber‐EP4, claudin‐4 had the highest specificity and PPV (100% for each), followed by Ber‐EP4. Claudin‐4 showed high sensitivity (93.7%), albeit lower than MOC‐31. MOC‐31 had the lowest specificity and PPV but the highest sensitivity and NPV. Ber‐EP4 had the lowest sensitivity (91.6%). Conclusions: Claudin‐4 can be used as a single marker for carcinoma with high sensitivity and superior specificity compared with MOC‐31 and Ber‐EP4. Mesothelial lineage can be ruled out when claudin‐4 is positive. In equivocal cytology samples with few scattered cells of interest, a panel of claudin‐4 and Ber‐EP4 results in the highest combined sensitivity and specificity. The findings in this study demonstrate the high sensitivity and superior specificity of claudin‐4 as a single marker for carcinoma in cytology specimens and its ability to rule out mesothelial lineage with high certainty. The authors also identify the highly sensitive and specific combination of claudin‐4 and Ber‐EP4 in diagnosing equivocal specimens previously categorized as atypical or suspicious. [ABSTRACT FROM AUTHOR]

There is clear evidence that the phenotypic modulation of smooth muscle cells (SMCs) contributes to the pathophysiology of vascular disease. Phenotypic modulation refers to the unique ability of SMCs to alter their phenotype in response to extracellular stimuli and is hallmarked by the loss of SMC marker gene expression. The transcription factor Kruppel-like factor 4 (KLF4) is a known powerful negative regulator of SMC marker gene expression that works, in part, by decreasing the expression of the serum response factor (SRF) myocardin. KLF4 is not expressed in healthy adult SMCs but is increased in SMCs in response to vascular injury in vivo or PDGF-BB treatment in vitro. The aim of the present study was to determine the molecular mechanisms that regulate the expression of KLF4 in phenotypically modulated SMCs. The results demonstrated that the transcription factor stimulating protein-1 (Sp1) regulated the expression of KLF4 in SMCs. The KLF4 promoter contains three consensus Sp1 binding sites. Using a series of truncated KLF4 promoters, we showed that only fragments containing these Sp1 sites could be activated by PDGF-BB. In addition, overexpression of Sp1 alone was sufficient to increase the activity of the KLF4 promoter. Moreover, inhibiting Sp1 expression with small-interfering RNA attenuated the effects of PDGF-BB on KLF4 expression. Mutation of the three Sp I sites within the KLF4 promoter abolished both baseline and PDGF-BB-induced activity. Finally, the results demonstrated enhanced Sp1 binding to the KLF4 promoter in SMCs treated with PDGF-BB in vitro and following vascular injury in vivo. Taken together, the results suggest a novel role for Sp1 in increasing the expression of KLF4 in phenotypically modulated SMCs. Kruppel-like factor 4; stimulating protein-1; platelet-derived growth factor-BB; vascular injury