A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning.

Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image-based histopathologic images and identifies Silva patterns with high accuracy. Initially, a total of 202 patients with EACs and histopathologic slides were obtained from Qilu Hospital of Shandong University for developing and internally testing the Silva3-AI model. Subsequently, an additional 161 patients and slides were collected from seven other medical centers for independent testing. The Silva3-AI model was developed using a vision transformer and recurrent neural network architecture, utilizing multi-magnification patches, and its performance was evaluated based on a class-specific area under the receiver-operating characteristic curve. Silva3-AI achieved a class-specific area under the receiver-operating characteristic curve of 0.947 for Silva A, 0.908 for Silva B, and 0.947 for Silva C on the independent test set. Notably, the performance of Silva3-AI was consistent with that of professional pathologists with 10 years' diagnostic experience. Furthermore, the visualization of prediction heatmaps facilitated the identification of tumor microenvironment heterogeneity, which is known to contribute to variations in Silva patterns.

Direct modulation of firing activity by dopamine D2 like receptors in the globus pallidus of both normal and parkinsonian rats.

The globus pallidus occupies a critical position in the indirect pathway of the basal ganglia circuit, which regulates movement under both normal and pathological conditions. Previous studies have shown that the globus pallidus receives dopaminergic innervation from the axonal collaterals of nigrostriatal fibers. Both dopamine D1 and D2 like receptors are expressed in the globus pallidus. The present study was aimed to investigate the direct in vivo electrophysiological effects of dopamine D2 like receptors in the globus pallidus of both normal and parkinsonian rats. Extracellular recordings of multi-barreled microelectrode were used in the present study. In normal rats, micro-pressure ejection of dopamine D2 like receptor agonist quinpirole induced different effects on the firing rate of globus pallidus neurons. In 24 out of the 61 pallidal neurons, quinpirole significantly increased the firing rate by (62.7 ± 11.2)%. In another 16 neurons, quinpirole decreased the spontaneous firing rate by (37.5 ± 2.9)%. Furthermore, co-application of dopamine D2 like receptor antagonist, sulpride, blocked quinpirole-induced modulation of the firing rate of pallidal neurons. On the 6-hydroxydopamine (6-OHDA) lesioned side of parkinsonian rats, quinpirole increased the firing rate in 25 out of the 47 pallidal neurons by (64.2 ± 10.1)%, while decreased the firing rate in 11 neurons by (51.9 ± 6.2)%. Our findings suggest that activation of pallidal dopamine D2 like receptors may bidirectionally modulate the spontaneous firing of globus pallidus neurons in both normal and parkinsonian rats.

MicroRNA­153 may act as a potential biomarker and prognostic indicator of patients with gastric cancer.

MicroRNA (miR/miRNA)-153, as a novel tumor-related miRNA, has been found to be aberrantly expressed in different types of cancer; however, to the best of our knowledge, the role of miR-153 in gastric cancer (GC) remains unclear. The present study demonstrated that miR-153 expression was markedly decreased in GC, including GC cell lines and culture medium, GC tissues, and serum samples, based on reverse transcription-quantitative PCR, and this was further confirmed by fluorescence in situ hybridization. Transfection with miR-153 mimics inhibited proliferation and migration, and promoted apoptosis in GC cells. The serum expression levels of miR-153 were decreased in 59 patients with GC compared with those of 9 healthy controls, and more decreased in advanced GC compared with early-stage GC, suggesting that miR-153 was associated with tumor progression. Furthermore, serum miR-153 was expressed at significantly lower levels in patients with GC with larger tumor size (≥4 cm; P=0.013), poor differentiation and signet histology (P=0.013), lymph node metastasis (P=0.025) and advanced tumor stage (TNM stage III and IV; P=0.048) compared with patients with a smaller tumor size (<4 cm), well and moderate differentiation, no lymph node metastasis, and TNM stage I and II, respectively. In conclusion, the present study revealed that low miR-153 expression was associated with poor prognosis in GC and miR-153 may potentially act as a tumor biomarker and therapeutic target in GC.

RETRACTED: KDM4A promotes the growth of non-small cell lung cancer by mediating the expression of Myc via DLX5 through the Wnt/ß-catenin signaling pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors as they "found major problems in the data and conclusions through their later research". 1. When the authors performed flow cytometry to detect apoptosis, the Annexin-V-coupled fluorophore they used was Fluor 647 (as described in the Methods section), which was incorrectly labelled as the Annexin-V-coupled fluorophore as FITC in their Figures (Fig. 5E, 7C and Fig. S1D). The excitation wavelengths of Alexa Fluor 647 (594/633 nm) are different from that of FITC (490 nm/520 nm), this mistake would lead to unreliability of their data. 2. The authors discovered a major error during the traceability of the antibodies used in the experiments. The primary antibody they used to detect KDM4A was actually a primary antibody for KDM6B, as evidenced by the western blots. KDM6B is a 177-kDa protein (consistent with the kDa shown in Fig. 1K and Fig. 2B), while KDM4A is a 150-kDa protein. 3. Lastly, the authors carelessly mislabeled KDM4A as KDM4B in Fig. 7. The authors and the Editors believe that the conclusions of the paper are not dependable, so we have decided to retract the paper. Apologies are offered to readers of the journal that this was not detected during the submission process.

MiR-382 targets GOLM1 to inhibit metastasis of hepatocellular carcinoma and its down-regulation predicts a poor survival.

Accumulating evidences have illuminated that an amount of microRNAs are involved in human diseases including hepatocellular carcinoma (HCC). In this study, we found that the expression of miR-382 in HCC tissues was down-regulated compared with the non-cancerous tissues. Over-expression of miR-382 could significantly inhibit the migration and invasion of HCC cells in vitro and in vivo. Bioinformatic algorithms and luciferase reporter assays suggested that Golgi Membrane Protein 1 (GOLM1) was a direct target of miR-382. Interestingly, we found the down-regulation of GOLM1 in HCC cells could rescue these cells from miR-382-mediated suppression of migration and invasion. Our findings might demonstrate that miR-382 inhibited the metastasis of HCC by targeting GOLM1. Furthermore, cox proportional hazards analyses suggested that low expression of miR-382 was an independent prognostic factor for the HCC patients. In conclusion, our results highlighted that miR-382, a novel prognostic factor, target GOLM1 to inhibit metastasis of hepatocellular carcinoma.

Mismatch repair-deficient status associates with favorable prognosis of Eastern Chinese population with sporadic colorectal cancer.

The present study aimed to investigate the expression level of DNA mismatch repair gene (MMR) in in sporadic colorectal cancer (SCRC) in eastern China, and to investigate the association between MMR status and prognosis of patients with SCRC. Patient archives from the Department of Gastrointestinal Surgery of Weihai Municipal Hospital (Weihai, China) were retrospectively collected between January 2011 and January 2012. Of the 221 consecutive patients identified, 192 patients who met the criterion were deemed eligible for inclusion. Immunohistochemistry (IHC) was conducted to detect the expression of MMR proteins MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2, mismatch repair system component (PMS2) expression and mutation in sporadic colorectal cancer (SCRC). Kaplan-Meier plots and log-rank tests were performed to conduct survival analysis and Cox proportional hazard regression models were conducted to determine independent prognostic factors. The total rate of deficient MMR (dMMR) was 14.58% (28/192): MSH6, 0.52% (1/192); PMS2, 4.17% (8/192); MSH2/MSH6, 3.65% (7/192); and MLH1/PMS2, 6.25% (12/192). The dMMR group had a significantly longer overall survival time compared with proficient MMR (pMMR) group (P=0.017). Disease-free survival time of dMMR group was also longer than pMMR group (P=0.027). Multivariate analysis using the Cox regression model confirmed that MMR status was an independent prognostic factor for SCRC. Loss of MMR expression was indicative of a favorable outcome for patients with SCRC, and MMR status could be viewed as an independent prognostic factor.