WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of lung, breast, and ovarian adenocarcinomas in serous effusions

The distinction between metastatic adenocarcinomas of lung (LAC), breast (BAC), and ovary (OAC) in serous effusions can be very difficult since they all can present as tight cell clusters. This is particularly challenging when the malignant effusion is the patient's initial presentation or when the patient has a history of more than one primary. The aim of this study is to evaluate the usefulness of WT1, monoclonal CEA (mCEA), TTF1, and CA125 antibodies in the differential diagnosis of metastatic adenocarcinoma from the lung, breast and ovary in serous effusions. Forty-six samples of serous effusions with their corresponding cell blocks were retrieved from our hospital computer system, including 13 BACs, 13 LACs, and 20 OACs. The diagnoses were confirmed by the surgical resection. Formalin-fixed and paraffin-embedded cell block sections were immunostained for WT1, mCEA, TTF1, and CA125. Two observers blindly reviewed the immunostained slides without knowledge of the previous clinical or histologic diagnoses. The staining intensity was graded semiquantitatively as negative, 0; weak, 1+; moderate, 2+; and strong, 3+. The percentage of positively staining cells was estimated. The distribution patterns of reactivity for WT1 and TTF1 were recorded as nuclear, and mCEA and CA125 as membranous stain. Metastatic OACs showed positive immunoreactivity to WT1 in 19/20 (95%) cases, CA125 in 20/20 (100%), and all showed negative reaction for both mCEA (0/20, 0%) and TTF1 (0/20, 0%). BAC showed positive reaction in 6/13 (46%) cases to CA125 and mCEA. Staining pattern was diffuse for CA125 and focal for mCEA. Only 2/13 (15%) were positive for WT1, while all of 13 BAC cases (0/13, 0%) were negative for TTF1. LAC showed positive immunoreactivity for TTF1 in 9/13 (69%) with a characteristic nuclear staining pattern, but only 3/13 (23%) were focally stained for WT1. In addition, 8/13 (62%) of LAC cases were positive for both CA125 and mCEA. Our results demonstrate that the WT1 stain is specific for metastatic carcinoma of ovarian primary, showing a high sensitivity. In addition, CA125 stain is very sensitive for OACs, but could be positive in about a half of LAC and BAC cases. An immunostaining pattern of positive mCEA as well as negative WT1 rules out OACs, raising the possibility of LACs and BACs. A positive TTF1 staining supports the diagnosis of metastatic carcinoma originating from lung rather than breast, while a negative TTF1 favors the diagnosis of a breast primary. Immunohistochemical studies with WT1, TTF1, and mCEA antibodies are useful in the differential diagnosis of metastatic adenocarcinomas of lung, breast, and ovary. Diagn. Cytopathol. 2007;35:370–375. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56105/1/20643_ftp.pd

Experimental study on secondary bearing mechanism of weakly cemented broken rock mass

In order to study the secondary bearing mechanism of weakly cemented broken surrounding rock, the surface of granite, limestone and mudstone broken rock samples were poured by cement slurry, and the weakly cemented rock mass was formed by static pressure infiltration method, and then an uniaxial loading test was carried out. The results show that the weakly cemented broken rock mass has a certain bearing capacity, but the bearing capacity is low, and the dispersion is high. The secondary bearing capacity of weakly cemented rock mass is affected by factors such as broken rock strength, rock particle size and rock gradation. The larger the rock particle size and strength are, the higher the secondary bearing capacity of the weakly cemented rock mass is. The average bearing capacity of the mudstone weak cementation specimen is 18.77 kN, and the residual bearing capacity is 1.46 kN, and a dispersion coefficient is 0.34. The average bearing capacity of granite is 343.65 kN, and the residual carrying capacity is 25.81 kN, and a dispersion coefficient is 0.11. The average bearing capacity of limestone is 367.22 kN, and the residual carrying capacity is 22.78 kN, and a dispersion coefficient is 0.3. After a certain grading, the average residual secondary bearing capacity of the weakly cemented rock mass is obviously improved, and the dispersion coefficient of peak bearing capacity is reduced. The grading scheme 1 has an average peak carrying capacity of 330.06 kN, a residual carrying capacity of 34.56 kN, and a dispersion coefficient is 0.07. The averaging scheme 2 has an average peak carrying capacity of 297.8 kN, a residual carrying capacity of 29.86 kN, and a dispersion coefficient is 0.14. The cementation regeneration mechanism of the broken rock mass mainly includes the cement-bonding effect of the cement slurry inside and on the broken rock mass. Under the loaded condition, the internal load-bearing network of the broken rock mass is the main mechanism for the secondary load of the broken rock mass, and the stability of the force-chain network is affected by the constraint. After the loss of the confinement, the force chain network fails, and the residual secondary bearing mechanism of the weakly cemented broken rock mass is transformed into the friction between the broken rock masses in the residual core rock pillar

Remote Medication Status Prediction for Individuals with Parkinson's Disease using Time-series Data from Smartphones

Medication for neurological diseases such as the Parkinson's disease usually happens remotely away from hospitals. Such out-of-lab environments pose challenges in collecting timely and accurate health status data. Individual differences in behavioral signals collected from wearable sensors also lead to difficulties in adopting current general machine learning analysis pipelines. To address these challenges, we present a method for predicting the medication status of Parkinson's disease patients using the public mPower dataset, which contains 62,182 remote multi-modal test records collected on smartphones from 487 patients. The proposed method shows promising results in predicting three medication statuses objectively: Before Medication (AUC=0.95), After Medication (AUC=0.958), and Another Time (AUC=0.976) by examining patient-wise historical records with the attention weights learned through a Transformer model. Our method provides an innovative way for personalized remote health sensing in a timely and objective fashion which could benefit a broad range of similar applications.Comment: Accepted to ICDH-2023. Camera ready with supplementary materia

hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue

Telomerase plays a role in the immortalization of cells and carcinogenesis. Previous studies have yielded conflicting results on whether human telomerase RNA (hTER) expression differs in nevi, atypical nevi and melanomas using polymerase chain reaction-based telomeric repeat amplification protocol or in situ hybridization assays. The aim of this study was to evaluate human telomerase reverse transcriptase (hTERT) staining in melanocytic lesions on paraffin-embedded tissues. Methods:  Paraffin-embedded sections from 12 acquired nevi, seven dysplastic nevi, 11 Spitz nevi, eight primary invasive melanomas, and three metastatic melanomas were studied for staining intensity (0–3+) and percentage of labeled cells with anti-hTERT. Results:  hTERT staining was observed in most cells (>75%), in all but three lesions, and was of greater intensity in the nucleus, especially the nucleolus, compared with the cytoplasm. Spitz nevi tended to have weaker hTERT staining (mean = 1.7) compared with acquired nevi (mean = 2.2), dysplastic nevi (mean = 2.4), primary melanomas (mean = 2.4), or metastatic melanomas (mean = 3). Conclusions:  Although telomerase activity was weaker in Spitz nevi, there was overlap with other nevi and primary invasive melanomas in our small series. Thus, hTERT expression does not appear to be a reliable adjunct to the histological diagnosis of primary melanocytic lesions. Fullen DR, Zhu W, Thomas D, Su LD. hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75519/1/j.0303-6987.2005.00403.x.pd

Case Report Primary thyroid spindle cell tumors: spindle cell variant of papillary thyroid carcinoma?

Abstract: Primary thyroid spindle cell tumors or spindle cell component in the thyroid tumors are very rare. The spindle tumor cells were positive for thyroid papillary carcinoma markers. So these tumors were diagnosed as spindle cell variant of papillary thyroid carcinoma (PTC). To further delineate clinico-pathological features of primary thyroid spindle cell tumors and discuss differential diagnosis, we reported a 67-year-old man with a mass in the right thyroid without clinical symptom. Microscopy revealed that an encapsulated tumor with lot criss spindle cells arranged in bundles. Nuclear grooves were easy to see and rare displayed pseudoinclusions. Immunohistochemical studied showed that the spindle cells were all strong positive for TTF-1, Pax-8, thyroglobulin. Rare follicular were seen in the periphery of the tumor near the thyroid tissue. The cells formed follicular but the spindle tumor cells were positive for pan-keratins. The pathological diagnosis was primary thyroid spindle cell tumors, suspected spindle cell variant of PTC. Primary thyroid spindle cell tumors were presence and without the unified name. The further reports and more discussion were need about these tumors

Two Novel AGXT Mutations Cause the Infantile Form of Primary Hyperoxaluria Type I in a Chinese Family: Research on Missed Mutation

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype–genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family

HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis

Nasopharyngeal carcinoma (NPC), as one of the most prevalent malignancies in the head and neck region, still lacks a complete understanding of its pathogenesis. Presently, radiotherapy, concurrent chemoradiotherapy, and targeted therapy stand as the primary modalities for treating NPC. With advancements in medicine, the cure rates for nasopharyngeal carcinoma have been steadily increasing. Nevertheless, recurrence and metastasis persist as the primary reasons for treatment failure. Consequently, a profound exploration of the molecular mechanisms underlying the occurrence and progression of nasopharyngeal carcinoma, along with the exploration of corresponding therapeutic approaches, becomes particularly imperative in the quest for comprehensive solutions to combat this disease. High mobility group AT-hook 2 (HMGA2) is a pivotal protein capable of altering chromatin structure, regulating gene expression, and influencing transcriptional activity. In the realm of cancer research, HMGA2 exhibits widespread dysregulation, playing a crucial role in nearly all malignant tumors. It is implicated in various tumorigenic processes, including cell cycle regulation, cell proliferation, epithelial-mesenchymal transition, angiogenesis, tumor invasion, metastasis, and drug resistance. Additionally, HMGA2 serves as a molecular marker and an independent prognostic factor in certain malignancies. Recent studies have increasingly unveiled the critical role of HMGA2 in nasopharyngeal carcinoma (NPC), particularly in promoting malignant progression, correlating with tumor resistance, and serving as an independent adverse prognostic factor. This review focuses on elucidating the oncogenic role of HMGA2 in NPC, suggesting its potential association with chemotherapy resistance in NPC, and proposing its candidacy as an independent factor in nasopharyngeal carcinoma prognosis assessment

Application of particle swarm optimization-based least square support vector machine in quantitative analysis of extraction solution of yangxinshi tablet using near infrared spectroscopy

A particle swarm optimization (PSO)-based least square support vector machine (LS-SVM) method was investigated for quantitative analysis of extraction solution of Yangxinshi tablet using near infrared (NIR) spectroscopy. The usable spectral region (5400–6200 cm-1) was identified, then the first derivative spectra smoothed using a Savitzky–Golay filter were employed to establish calibration models. The PSO algorithm was applied to select the LS-SVM hyperparameters (including the regularization and kernel parameters). The calibration models of total flavonoids, puerarin, salvianolic acid B and icariin were established using the optimum hyperparameters of LS-SVM. The performance of LS-SVM models were compared with partial least squares (PLS) regression, feed-forward back-propagation network (BPANN) and support vector machine (SVM). Experimental results showed that both the calibration results and prediction accuracy of the PSO-based LS-SVM method were superior to PLS, BP-ANN and SVM. For PSO-based LS-SVM models, the determination coefficients (R2) for the calibration set were above 0.9881, and the RSEP values were controlled within 5.772%. For the validation set, the RMSEP values were close to RMSEC and less than 0.042, the RSEP values were under 8.778%, which were much lower than the PLS, BP-ANN and SVM models. The PSO-based LS-SVM algorithm employed in this study exhibited excellent calibration performance and prediction accuracy, which has definite practice significance and application value