The efficacy of articaine in pain management during endodontic procedures in pediatric patients.

OBJECTIVE: This trial aimed to study the efficacy of articaine in pain management during endodontic procedures in pediatric patients. METHODS: Ninety-eight children who received endodontic painless treatment were collected and randomly divided into the control group and observation group, with 49 cases in each group. The control group received infiltration anesthesia with lidocaine, and the observation group received infiltration anesthesia with articaine. Anesthesia effect, anesthesia onset time, sensory recovery time, duration of anesthesia, pain intensity, blood pressure, heart rate, and adverse reactions were compared. RESULTS: The effective rate of anesthesia in the observation group was higher than that in the control group. The anesthesia onset time and sensory recovery time were shorter, the duration of anesthesia was longer, and the VAS score and facial expression score were lower in the observation group than in the control group. The heart rate of the observation group was lower, and diastolic blood pressure was higher than those of the control group. The total incidence of adverse reactions in the observation group was lower than that in the control group. CONCLUSION: In the treatment of dental pulp diseases in children, the use of articaine can achieve better anesthesia effect and rapid onset of anesthesia and has less impact on the patient's blood pressure and heart rate, but it also can relieve pain and has good safety after the use of medication. It is worthy of clinical application.

Construction of a cold island network for the urban heat island effect mitigation.

The urban heat island (UHI) effect seriously challenges sustainable urban development strategies and livability. Numerous studies have explored the UHI problem from the perspective of isolated blue and green patches, ignoring the overall function of cold island networks. This study aims to explore the construction method of cold island network by integrating scattered cold island resources, rationally guiding urban planning and construction, and providing effective ideas and methods for improving the urban thermal environment. Taking the central city of Fuzhou as an example, the identification of the cold island core source (CICS) was optimized by applying relative land surface temperature (LST), morphological spatial pattern analysis, and landscape connectivity analysis. The combined resistance surface was constructed based on a spatial principal component analysis. Subsequently, the cold island network was constructed by applying circuit theory and identifying the key nodes. The results showed that the central and eastern parts of the study area experienced the most significant UHI effects and there was a tendency for them to cluster. Overall, 48 core sources, 104 corridors, 89 cooling nodes, and 34 heating nodes were identified. The average LST of the CICSs was 28.43 °C, significantly lower than the average LST of the entire study area (31.50 °C), and the 104 cold corridors were classified into three categories according to their importance. Different targeting measures should be adopted for the cooling and heating nodes to maintain the stability of the cold island network and prevent the formation of a heat network. Finally, we suggest a model for urban cold island network construction and explore methods for mitigating issues with UHI to achieve proactive and organized adaptation and mitigation of thermal environmental risks in urban areas, as well as to encourage sustainable urban development.

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: Evaluation of dermal safety, intra-mammary drug distribution, and biologic effects.

Breast cancer prevention only requires local exposure of the breast to active drug. However, oral preventive agents entail systemic exposure, causing adverse effects that limit acceptance by high-risk women. Drug-delivery through the breast skin is an attractive option, but requires demonstration of dermal safety and drug distribution throughout the breast. We formulated the tamoxifen metabolite (E/Z)-endoxifen for transdermal delivery and tested it in a placebo-controlled, double-blinded Phase I trial with dose escalation from 10 to 20 mg daily. The primary endpoint was dermal toxicity. Thirty-two women planning mastectomy were randomized (2:1) to endoxifen-gel or placebo-gel applied to both breasts for 3-5 weeks. Both doses of endoxifen-gel incurred no dermal or systemic toxicity compared to placebo. All endoxifen-treated breasts contained the drug at each of five sampling locations; the median per-person tissue concentration in the treated participants was 0.6 ng/g (IQR 0.4-1.6), significantly higher (p < 0.001) than the median plasma concentration (0.2 ng/mL, IQR 0.2-0.2). The median ratio of the more potent (Z)-isomer to (E)-isomer at each breast location was 1.50 (IQR 0.96-2.54, p < 0.05). No discernible effects of breast size or adiposity on tissue concentrations were observed. At the endoxifen doses and duration used, and the tissue concentration achieved, we observed a non-significant overall reduction of tumor proliferation (Ki67 LI) and significant downregulation of gene signatures known to promote cancer invasion (FN1, SERPINH1, PLOD2, PDGFA, ITGAV) (p = 0.03). Transdermal endoxifen is an important potential breast cancer prevention agent but formulations with better dermal penetration are needed.

Analysis of Hemostatic Effect and Safety of Local Spray Treatment With Hemocoagulase Bothrops Atrox for Injection After Resection of Colon Polyps.

Context: Postoperative bleeding after resection of colon polyps (CPs) is an extremely common adverse event with endoscopic treatment. Hemocoagulase Bothrops Atrox (HBA) is a newly discovered hemostatic substance that contains thrombin-like and coagulation kinase-like enzymes. However, research is lacking about its use for the treatment of intestinal polyps. Objective: The study intended to examine the hemostatic efficacy and safety of a local spray treatment with HBA, derived from HBA for injection, after CP resection, to provide a new hemostatic method, support HBA's use, and provide evidence for clinical decision making. Design: The research team performed a randomized controlled study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants: Participants were 200 patients with CP who received treatment at the hospital between December 2020 and December 2022. Intervention: The research team divided participants into two groups with 100 participants each, an intervention group and a control group, using the random number expression method. For hemostasis, the intervention group received a local spray treatment that used HBA for injection, and the control group received metal-clip closure or electrocoagulation. Outcome Measures: The research team measured: (1) the hemostatic efficacy; (2) clinical outcomes-time to hemostasis, hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding; (3) at baseline and at 24h postintervention, the coagulation function-prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); (4) at baseline and at 24h postintervention, PLT parameters-platelet count (PLT), procalcitonin (PCT), and mean platelet volume (MPV); (5) economic effects-total number of participants with hemostasis, hospital days, and total hospital costs; and (6) adverse reactions. Results: The total hemostatic efficacy for the intervention group was significantly higher than that of the control group (P = .027), and the time to hemostasis was significantly shorter (P < .001) and the hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding were all significantly lower than those of the control group, at P = .009, P = .009, and P = .048, respectively. In addition, the intervention group's postoperative PT, TT, APTT, FIB, and MPV were all significantly lower than those of the control group (all P < .05), while its PLT and PCT were significantly higher than those of the control group (both P < .05). The intervention group's total number of participants with hemostasis, participants with hemostasis, hospital days, and total cost were significantly lower than those of the control group (all P < .05), while no significant difference existed between the groups in the incidence of adverse effects (P > .05). Conclusions: HBA has an excellent hemostatic effect on intestinal polypectomy, with convenient use and high safety. In the future, popularizing the use of HBA in the treatment of intestinal polypectomy can not only effectively guarantee the postoperative safety of patients but also could reduce their economic burden and improve the quality of clinical medical services.

Breast Cancer With a HER2 FISH Group 2 Result: Should HER2 Tests be Repeated?

BACKGROUND: Breast cancer with fluorescence in situ hybridization (FISH) group 2 pattern (HER2 <4 and HER2/CEP17 ratio ≥2, a subset of monosomy CEP17) was historically considered HER2-positive, but mostly HER2-negative according to updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines unless 3+ by immunohistochemistry (IHC). Therapeutic relevance of this group remained elusive, therefore we assessed if repeat IHC and FISH can assist final HER2 classification. PATIENT AND METHODS: We retrospectively reviewed HER2 FISH performed at our institution from 2014 to 2018 and identified 23 of 3554 (0.6%) breast cancer cases with at least one-time measurement of HER2 FISH categorized as group 2. Repeat HER2 tests were performed for cases with available alternative tumor samples and compared with initial testing following 2018 ASCO/CAP guidelines. RESULTS: Only 1 of 23 group 2 cases was HER2-positive, 0/18 in primary and 1/5 in metastatic/recurrent tumors. Of 13 primary tumors with repeat HER2 results; 10 (77%) remained HER2-negative; 3 (23%) changed from HER2-negative (group 2 and IHC 2+) to HER2-positive (group 1 and IHC 2+). Among 8 of these 13 patients receiving neoadjuvant systemic therapy containing anti-HER2 agent, 3 (38%) achieved pathologic complete response (pCR). Two of 3 pCR cases were HER2-positive converters on repeat testing. Three pCR cases were ER-negative or -low positive and Ki67 ≥40%, while 5 partial responders were ER-positive and Ki67 <40% (P < .05). CONCLUSION: Breast cancer with HER2 FISH group 2 result may represent heterogeneous populations of tumor cells being originated de novo or preferentially selected secondary to therapy. Repeat HER2 tests on alternative samples may be considered to guide anti-HER2 therapy.

Z-Endoxifen prevents aggressive mammary cancers in mice by inhibiting cell proliferation and creating a tumor suppressive microenvironment.

Aggressive estrogen receptor (ER) positive breast cancer is frequently tamoxifen-resistant; alternative endocrine approaches exist for therapy, but not for prevention, particularly in premenopausal women. We examined the efficacy of the selective ER modulator (Z-endoxifen) as monotherapy and in combination with the selective progesterone receptor modulators (onapristone and ulipristal acetate) in the tamoxifen-insensitive C3(1)/SV40TAg mouse mammary tumorigenesis model. Unlike tamoxifen at human equivalent dose (HED) 101 mg/day, endoxifen at HED 24 mg/day significantly increased latency and reduced tumor growth relative to untreated controls. Ulipristal acetate (UPA) at HED 81 mg/day also significantly increased latency however failed to inhibit tumor growth, while onapristone (HED 98 mg/day) had no tumor prevention efficacy in this model. Addition of UPA to endoxifen did not enhance preventive efficacy over endoxifen alone. The expression of genes associated with cell cycle, cell proliferation and extracellular matrix remodeling was similarly repressed by endoxifen and UPA however only endoxifen significantly downregulated prominent genes associated with poor prognosis (Col11a1, Il17b, Pdgfa, Tnfrsf11a). Our results indicate that endoxifen can prevent breast cancers, even when tamoxifen-resistant, through its role in favorable tissue remodeling and immunomodulation.

Application of the International System for Reporting Serous Fluid Cytopathology to pericardial fluid: Root cause analysis of indeterminate diagnoses, cytohistological correlation, and assessment of malignancy risk.

BACKGROUND: This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy (ROM) for each of the diagnostic categories. METHODS: All pericardial fluid cases at the Yale School of Medicine between January 1, 2017, and December 31, 2020, were reviewed. The diagnoses were reclassified into five categories according to the ISRSFC: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance parameters of each category were calculated. RESULTS: After reclassification, the distribution of 465 pericardial fluid cases in each category was as follows: ND, 19 (4.1%); NFM, 332 (71.4%); AUS, 21 (4.5%); SFM, 11 (2.4%); and MAL, 82 (17.6%). Confirmatory follow-ups were available for 16 ND (66.7%), 299 NFM (90%), 15 AUS (71%), 5 SFM (45.5%), and 30 MAL cases (36.6%). The ROM was 0% for ND, 1.3% for NFM (4 of 332), 20% for AUS (3 of 15), and 100% for both SFM (5 of 5) and MAL (27 of 27). The diagnostic performance was as follows: sensitivity, 87% (27 of 31); specificity, 100% (292 of 292); positive predictive value (PPV), 100% (27 of 27); negative predictive value (NPV), 98.6% (292 of 296); and diagnostic accuracy, 98.8% (319 of 323). CONCLUSIONS: The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, PPV, NPV, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting.

Diagnosis of acinic cell carcinoma of the salivary gland on cytology specimens: Role of NOR-1 (NR4A3) immunohistochemistry.

OBJECTIVES: Acinic cell carcinoma (AcCC) is often a challenging diagnosis on cytology. Recently, NOR-1 (NR4A3) has been demonstrated as a sensitive and specific marker for AcCC. Therefore, we conducted this study to evaluate NOR-1 expression in AcCC cytology specimens and to compare its reactivity in other salivary gland tumours (non-AcCC). METHODS: We retrospectively reviewed our database and selected cytology cases with available cell blocks, including 10 AcCC and 24 non-AcCC tumours (12 benign tumours and 12 malignant tumours). NOR-1 (1:50 dilution; SC393902 [H-7]; Santa Cruz Biotech) immunohistochemistry (IHC) was performed on all cases. RESULTS: All AcCC cases except two (2/10, 80%) showed positive nuclear staining of variable intensity for NOR-1, with the majority of cases (75%) demonstrating at least moderately intense nuclear expression. All non-AcCC cases were negative for NOR-1, demonstrating a specificity of 100%. CONCLUSION: We conclude that NOR-1 IHC is sensitive and very specific on cytology specimens and is able to distinguish AcCC from its mimickers reliably and classify them appropriately for further management.

GATA3 expression in primary lung carcinomas: correlation with histopathologic features and TTF-1, napsin A, and p40 expression.

This study assessed the expression of GATA3 in primary lung carcinomas and correlated it with tumor histology and immunostains routinely utilized in the work up of primary lung cancers. Tissue microarrays (TMAs) were constructed from a cohort of 184 non-small cell carcinomas, stained with GATA3, p40, TTF-1, and napsin A, and analyzed semi-quantitatively. All TMA cases with GATA3 expression were further analyzed using corresponding whole slide sections. Positive GATA3 staining was present in 16 cases (9%), including 7 squamous cell carcinomas (SqCCs) (4%), 4 adenocarcinomas (AdCs) (2%), 2 adenosquamous carcinomas (AdSqCs) (1%), 2 large cell carcinomas (LCCs) (1%), and 1 sarcomatoid carcinoma (SC) (<1%). Among tumor histotypes, SqCC was more likely to stain with GATA3 (7/49, 14%), while AdC was less likely (4/111, 4%) (p = 0.04). In GATA3-positive cases, high-level expression was observed in 9 cases (56%), including 5 p40-positive SqCCs (3 were nonkeratinizing), 1 p40-positive AdSqC (negative for TTF-1 and napsin A), and 1 AdC (solid), 1 LCC, and 1 SC, each negative for p40, TTF-1, and napsin A). Low-level GATA3 expression was found in 3 AdCs (1 was lepidic and 2 were acinar predominant), 2 SqCCs (keratinizing), 1 AdSqC, and 1 LCC. These findings indicate that GATA3 expression occurs in a minor but significant proportion of primary non-small cell lung carcinomas, most often involves SqCC, and tends to show increasing levels of expression in more poorly differentiated subtypes. Caution should be exercised when interpreting GATA3 expression, and a panel of immunostains should be utilized when assigning tumor origin.

CCL20/CCR6 Mediated Macrophage Activation and Polarization Can Promote Adenoid Epithelial Inflammation in Adenoid Hypertrophy.

Background: Adenoid hypertrophy (AH) is a chronic or acute obstruction-related ailment of the upper respiratory tract that arises as an inflammatory response to exposure of bacteria, viruses or allergies. Activation and polarization of macrophages are key processes in inflammation-related disorders like AH and CCL20/CCR6 axis is a critical therapeutic target. Purpose: To determine that CCL20/CCR6 mediated macrophage activation and polarization can promote adenoid epithelial inflammation in AH. Methods: To support this claim, CCL20 and CCR6 expressions were studied in clinical AH samples. In addition, the expressions of cytokines such as TNF-α, IL-1ß, IL-6, IL-17, IL-10 and TGF-ß were analysed. In vitro, human adenoid epithelial cells were co-cultured with polarized THP-1 and T lymphocyte H9 cells to study the expressions of several inflammatory markers. Results: The expressions of M1 macrophage markers CD86 and IL-17 were significantly increased, whereas the expressions of M2 macrophage markers CD206 and FOXP3 were significantly decreased. The THP-1 cells were successfully polarized to M0, M1 and M2 macrophages. The survival of macrophages improved after 24 hr of induction and enhanced TGF-ß expression was observed. The expressions of the inflammatory cytokines IL-6, TNF-α, IL-1ß and CCL20 increased significantly. Conclusion: Collectively, these results suggest that the CCL20/CCR6 mediated macrophage activation and polarization into M1-type macrophages can promote adenoid epithelial inflammation in AH. Further studies are warranted to determine the roles of inflammatory markers in the pathophysiology of AH and identifying potential targets.

Study on the Microclimate Effect of Water Body Layout Factors on Campus Squares.

Quantifying the water layout factors in a campus square helps to lay out water bodies more scientifically and utilize the microclimate effect to alleviate the heat and humidity of campus squares in summer. The West Gate Square of Fujian Agriculture and Forestry University in China has been used as the primary theoretical model, and the landscape pattern index from landscape ecology has been used to quantify the scale, shape, and dispersion of water bodies. Consider the typical weather, the summer solstice, as the experiment time. The relationship between the water body layout factors and cooling effect, the humidification effect, and the wind speed is clarified from both temporal and spatial perspectives. The data were analyzed with ENVI-met and Arcgis software. Then, the optimum campus square water body layout mode was concluded. The results show that: (1) The scale, dispersion, and shape of the water body has a significant effect on the campus temperature and humidity, while the effect on wind speed is not significant. (2) From the cooling and humidifying effect, the ranking of the regulating ability of the water body layout factors is scale > shape > dispersion; the ranking of the influence range is shape > scale > dispersion. (3) When the boundary of the square is determined, the optimum water body layout mode is that the water body area accounts for 36% of the total square area. The shape of the water body is concentrated and not dispersed square. When the water body layout is determined, the optimum layout mode of the boundary is length:width = 1:2.

Research Progress and Hotspot Evolution Analysis of Landscape Microclimate: Visual Analysis Based on CNKI and WOS.

With the increasing requirements of healthy habitat environments, landscape microclimates have been widely concerned. To comprehensively grasp the development history and research status of the landscape microclimates in China and other countries, CiteSpace software was used to comparatively analyze and visually present the literature related to landscape microclimates in CNKI and WOS databases for the past 20 years. The results show that: (1) The number of publications on landscape microclimate research shows an increasing trend in China and other countries, and the number of publications increased significantly after 2016. Although the number of publications by Chinese scholars is less than that of foreign scholars, they have developed rapidly in recent years, and their international influence has increased significantly. (2) A positive exchange has been formed among international scholars, and the number of collaborative studies has been increasing. China's microclimate research has formed relatively stable teams that have conducted numerous studies in the fields of urban communities, street greening, and plant communities, respectively. Although the links between research teams and institutions in China and other countries are relatively close, they still need to be further strengthened. (3) In the past decade, the theoretical system of landscape microclimates has been improved, and the research themes have become more concentrated, but it still has remained close to the early basic research. (4) Future research will remain centered on "mitigating the urban heat island effect" and "optimizing human heat perception". New topics such as "biodiversity", "carbon cycle", and "climate change" have been added. In conclusion, the research needs to continue to explore the evaluation system of microclimates and verify the evaluation index of outdoor thermal comfort for human thermal adaptation in different regions. The standards and systems of human habitat adapted to different regional characteristics should be formed.

The Clinical Manifestation of p.Asp50Asn Heterozygous Mutation of GJB2 Gene in 3 Members of a Family Is Similar to That of Clouston Syndrome.

Keratitis-ichthyosis-deafness (KID) syndrome has genetic heterogeneity, and the clinical manifestations of some patients may overlap with Clouston syndrome. A 34-year-old female patient came to our department with a complain of "sparse hair, rough skin, photophobia and deafness for more than 30 years." We found that the proband and two other family members (57-year-old mother and 4-year-old daughter) had similar clinical manifestations: systemic hair loss, generalized skin hyperkeratosis, especially in the metacarpophalangeal area. Subungual hyperkeratosis, finger/toenail dystrophy, as well as photophobia and epiphora. According to the investigation, one of the family members also had similar clinical manifestations (grandfather of the proband) and he's died. The other three members of the family had no hearing impairment, and all patients had typical nail dystrophy, hair loss and palmoplantar hyperkeratosis, similar like as seen in Clouston syndrome, so we suspected to diagnose the case as Clouston syndrome. However, after genetic testing, it was found that the proband, his mother and daughter all had p.Asp50Asn heterozygous mutations in the GJB2 gene, and no mutation was detected in GJB6. The modified diagnosis was KID syndrome.

Histology segmentation using active learning on regions of interest in oral cavity squamous cell carcinoma.

In digital pathology, deep learning has been shown to have a wide range of applications, from cancer grading to segmenting structures like glomeruli. One of the main hurdles for digital pathology to be truly effective is the size of the dataset needed for generalization to address the spectrum of possible morphologies. Small datasets limit classifiers' ability to generalize. Yet, when we move to larger datasets of whole slide images (WSIs) of tissue, these datasets may cause network bottlenecks as each WSI at its original magnification can be upwards of 100 000 by 100 000 pixels, and over a gigabyte in file size. Compounding this problem, high quality pathologist annotations are difficult to obtain, as the volume of necessary annotations to create a classifier that can generalize would be extremely costly in terms of pathologist-hours. In this work, we use Active Learning (AL), a process for iterative interactive training, to create a modified U-net classifier on the region of interest (ROI) scale. We then compare this to Random Learning (RL), where images for addition to the dataset for retraining are randomly selected. Our hypothesis is that AL shows benefits for generating segmentation results versus randomly selecting images to annotate. We show that after 3 iterations, that AL, with an average Dice coefficient of 0.461, outperforms RL, with an average Dice Coefficient of 0.375, by 0.086.

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Risk of malignancy assessment of the International System for Reporting Serous Fluid Cytopathology: Experience in a community hospital setting and comparison with other studies.

BACKGROUND: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was published recently to provide standard reporting terminology for serous fluid. To date, several ISRSFC reclassification studies have reported a wide range of diagnostic category frequency and the associated risk of malignancy (ROM). Herein, the authors applied the ISRSFC to report pleural and peritoneal effusions retrospectively in a community hospital setting. METHODS: With Internal Review Board approval, 446 peritoneal effusion specimens and 299 pleural fluid specimens from 576 patients in three community hospitals over a 12-month period were reviewed and reclassified according to the ISRSFC. RESULTS: After reclassification, in pleural effusions, 18 (5.0%) were nondiagnostic (ND), 273 (76.0%) were negative for malignancy (NFM), 18 (5.0%) were atypia of undetermined significance (AUS), 6 (1.7%) were suspicious for malignancy (SFM), and 44 (12.3%) were malignant (MAL). In peritoneal effusions, after reclassification, 11 (5.5%) were ND, 168 (77.1%) were NFM, 9 (4.1%) were AUS, 2 (0.9%) were SFM, and 27 (12.4%) were MAL. The calculated ROM was 0.0% for ND, 1.8% for NFM, 37.5% for AUS, 83.3% for SFM, and 100.0% for MAL in peritoneal effusions; and the ROM was 8.3% for ND, 1.2% for NFM, 44.4% for AUS, and 100.0% for both SFM and MAL in pleural effusions. Further analysis demonstrated notable heterogeneity among published ISRSFC reclassification studies, although the overall ROMs did not differ significantly from the ISRSFC-determined ROMs (all p values were > .05 for mean ROM comparisons). CONCLUSIONS: The findings suggested the necessity for each laboratory to perform its own ROM analysis based on its statistics for ISRSFC-tiered classification terminology.

Evaluation of TRPS1 Expression in Pleural Effusion Cytology Specimens With Metastatic Breast Carcinoma.

OBJECTIVES: Recent studies have shown that trichorhinophalangeal syndrome type 1 (TRPS1) is a sensitive and specific marker that shows positive staining in breast carcinoma. We conducted this study to evaluate the role of TRPS1 immunohistochemistry (IHC) in differentiating breast primary vs tumors from other primary sites in malignant pleural effusion cytology specimens (MPECSs). METHODS: We selected 61 MPECS cases with cell block material available to analyze TRPS1 IHC staining. Of these 61 cases, 38 cases were metastatic carcinoma (MC) from a breast primary. We primarily selected MC cases confirmed as breast origin based on GATA binding protein 3 IHC positivity, except in two of the cases. The remaining 23 MPECS cases were from various primary sites, including urothelial (n = 6), Müllerian (n = 6), lung adenocarcinoma (n = 6), malignant melanoma (MM; n = 3), and squamous cell carcinoma (SqCC; n = 2). RESULTS: TRPS1 expression was observed in 35 (92%) of 38 MCs of breast origin. The staining intensity was variable, with 18 (47%) cases showing strong nuclear expression. In comparison, no TRPS1 expression was seen in any cases of urothelial carcinoma, MM, and SqCC. However, four of six Müllerian MC cases demonstrated TRPS1 expression. CONCLUSIONS: TRPS1 is a new marker that can be used in an IHC panel to investigate breast origin in MPECS.

Comprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens.

BACKGROUND: Molecular testing to identify molecular alterations in pancreatic ductal adenocarcinoma (PDAC) has been increasingly requested because of potential therapeutic implications. In this study, we compared the performance of PDAC fine-needle aspiration (FNA), fine-needle biopsy (FNB), and resection specimens for comprehensive molecular analysis. METHODS: A next-generation sequencing-based Oncomine Comprehensive Assay (OCA) was used to analyze molecular alterations in FNA, FNB, or resection specimens. We examined adequacy and success rates for completion of molecular testing and catalogued molecular alterations in these specimen types. RESULTS: The cohort included 23 FNA, 20 FNB, and 27 resection cases. Gene mutation or amplification analysis was successful in 18 (78%) FNA and 16 (80%) FNB specimens, whereas gene fusion assessment succeeded in 12 (52%) FNA and 12 (60%) FNB samples. All 27 (100%) resection specimens were adequate for complete OCA. There were significant differences in success rates for mutation and amplification analysis between resection and FNA or FNB specimens (P < .01) but not between FNA and FNB samples (P > .05). Manual microdissection was less likely to be performed for FNA specimens than FNB or resection specimens (P < .01). KRAS mutation was the most common mutation identified (90%), followed by mutations in TP53 (64%), CDKN2A (25%), and SMAD4 (15%) genes. CONCLUSIONS: Our study demonstrated similar success rates for comprehensive molecular analysis using FNA and FNB specimens of PDAC, suggesting that FNA material could serve as an alternative source for comprehensive molecular testing. The molecular alterations identified in these specimens may have potential diagnostic and therapeutic implications.

Tourist Landscape Preferences in a Historic Block Based on Spatiotemporal Big Data-A Case Study of Fuzhou, China.

Historic blocks are valuable architectural and landscape heritage, and it is important to explore the distribution characteristics of tourists to historic blocks and their landscape preferences to realize the scientific construction and conservation of historic blocks and promote their sustainable development. At present, few studies combine the analysis of tourist distribution characteristics with landscape preferences. This study takes the historic block of Three Lanes and Seven Alleys in Fuzhou as an example, combines field research and questionnaires to construct a landscape preference evaluation indicator system for the historic block, measures the distribution characteristics of tourists in the block through the heat value of tourist flow obtained from the Tencent regional heat map, and analyses the influence of landscape preference indicators on the heat value of tourist flow in the block through stepwise multiple linear regression. The research shows that: (1) the spatial and temporal variation in the heat value of tourist flow tends to be consistent throughout the block, from 7 a.m. to 6 p.m., showing a "rising, slightly fluctuating and then stabilizing" state, both on weekdays and on weekends. (2) The factors influencing the heat value of tourist flow in the different spatial samples are various, with commercial atmosphere, plant landscape, accessibility of the road space, architecture, and the surrounding environment having a significant impact on the heat value of tourist flow. Based on the analysis of the landscape preferences of tourists in the historic block, a landscape optimization strategy is proposed to provide a reference for the management and construction of the block.

Somatic Mutation of BAP1 Can Lead to Expression Loss in Non-Small Cell Lung Carcinoma: Next Generation Sequencing and IHC Analysis in A Large Single Institute Cohort.

Introduction. As a tumor suppressor, germline and somatic inactivation of BRCA1 associated protein 1 gene (BAP1) is a common finding in mesothelioma, melanocytic tumors, clear cell renal cell carcinoma and several other epithelial, mesenchymal and neural tumors. Incidence of BAP1 genetic alterations and subsequent expression loss has not been well established in non-small cell lung carcinoma (NSCLC) by large-scale studies. Design. After IRB approval, a total of 356 NSCLC cases of our institution between July 2016 and June 2020 were reviewed. The study cohort consisted of 214 (60%) adenocarcinomas, 89 (25%) squamous cell carcinomas, and 53 (15%) diagnosed as "non-small cell lung carcinoma" without specified subtype. All tumors underwent comprehensive target cancer gene next generation sequencing (Oncomine Assay). The protein expression status of BAP1 was subsequently evaluated by immunohistochemistry. Results. BAP1 somatic mutations were detected in 8 NSCLC tumors (incidence: 2.2%). Tumors harboring BAP1 mutations were all diagnosed at advanced stage and carried at least one additional genetic alteration. Immunohistochemically, four tumors showed complete loss of BAP1 protein expression, including two adenocarcinomas which harbored different missense BAP1 mutations and another two with bioinformatically predicated deleterious frameshifting mutations. Conclusion. Compared with known BAP1 loss associated other malignancies, such as mesothelioma, inactivation of BAP1 by somatic mutation is a rare occurrence in NSCLC. BAP1 mutations and loss of expression in NSCLC are accompanied by other complex genetic alternations, suggesting BAP1 mutation maybe a late event NSCLC carcinogenesis.