Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

Emerging and legacy per- and polyfluoroalkyl substances in house dust from South China: Contamination status and human exposure assessment.

Our study investigated a large variety of per- and polyfluoroalkyl substances (PFASs) in house dust collected from Guangzhou, South China during 2015-2018. The perfluorobutane sulfonic acid (PFBS) exhibited the highest median concentration (17.6 ng/g), followed by linear perfluorooctanoic acid (L-PFOA; 4.8 ng/g), linear perfluorooctane sulfonic acid (L-PFOS; 4.2 ng/g), 6:2 fluorotelomer phosphate diester (6:2 diPAP; 3.4 ng/g), perfluorodecanoic acid (PFDA; 1.2 ng/g) and perfluoroundecanoic acid (PFUdA; 1.2 ng/g), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA; 1.1 ng/g). Total concentrations of PFASs (median: 53 ng/g) were generally within the 25-50 percentile of the concentration range reported in global studies. However, our samples exhibited composition profiles different from those reported in many other regions. Analysis based on this and previous studies revealed that the compositions in house dust from East Asia, North America, and Europe exhibit a region-specific pattern. This may indicate region-specific market demands, application patterns, as well as associated human exposure risks. Exploration of dwelling characterizations suggested that renovation history appeared to be a significant factor influencing PFAS concentrations in house dust, although other factors may exist and play a role. Estimation of daily intakes via dust ingestion and dermal contact indicates low exposure risks from these two pathways. However, the PFAS chemical-specific biological effects, possible mixture effects, as well as additional exposure pathways, imply that the risk from indoor PFAS exposure should not be overlooked.

Reproducibility and relative validity of a semi-quantitative food frequency questionnaire for the Chinese lactating mothers.

BACKGROUND: The dietary nutritional status of the lactating mothers is related to maternal health and has a significant impact on the growth and development of infants through the secretion of breast milk. The food frequency questionnaire (FFQ) is the most cost-effective dietary assessment method that can help obtain information on the usual dietary pattern of participants. Until now, the FFQs have been used for different populations in China, but there are few FFQs available for the lactating mothers. We aimed to develop a semi-quantitative, 156-item FFQ for the Chinese lactating mothers, and evaluate its reproducibility and relative validity. METHODS: A total of 112 lactating mothers completed two FFQs and one 3-d dietary record (3DR). The first FFQ (FFQ1) was conducted during postpartum at 60-65 days and the second FFQ (FFQ2) during subsequent follow-up at 5 weeks. The 3DR was completed with portion sizes assessed using photographs taken by the respondent before and after eating (instant photography) 1 week after FFQ1. RESULTS: For reproducibility, the Spearman's correlation coefficients for food ranged from 0.34 to 0.68, and for nutrients from 0.25 to 0.61. Meanwhile, the intra-class correlation coefficients for food ranged from 0.48 to 0.87, and for nutrients from 0.27 to 0.70. For relative validity, the Spearman's correlation coefficients for food ranged from 0.32 to 0.56, and for nutrients from 0.23 to 0.72. The energy-adjusted coefficients for food ranged from 0.26 to 0.55, and for nutrients from 0.22 to 0.47. Moreover, the de-attenuation coefficients for food ranged from 0.34 to 0.67, and for nutrients from 0.28 to 0.77. The Bland-Altman plots also showed reasonably acceptable agreement between the two methods. CONCLUSIONS: This FFQ is a reasonably reproducible and a relative valid tool for assessing dietary intake of the Chinese lactating mothers.

Colon perforation due to cytomegalovirus infection in a patient with idiopathic hypereosinophilic syndrome: a case report.

BACKGROUND: Hypereosinophilic syndrome (HES) is a very rare disease and usually treated with corticosteroids. Gastrointestinal (GI) cytomegalovirus (CMV) infection is also rare but frequent in patients with immunocompromised status. These two related diseases present with similar manifestations, and may result in a life-threatening complication: perforation. However, the treatment strategies differ greatly. Here, we report a case of colon perforation due to cytomegalovirus infection in a patient with idiopathic HES. CASE PRESENTATION: A 41-year-old man with a history of HES was transferred to our hospital due to an acute onset of abdominal pain. During the treatment course of HES, this patient received CMV-DNA test with a result of < 2000 copies/ml. Computed tomography (CT) suggested colon perforation. An emergency surgery was performed immediately. Pathological diagnosis revealed CMV infection and infiltration of eosinophils. This patient received both anti-CMV therapy and immunosuppression therapy. Subsequently, the patient recovered and was discharged 25 days after the operation. CONCLUSION: During the course of HES treatment, CMV infection should be reconsidered if digestive symptoms relapse.

Does Low Maternal Exposure to Per- and Polyfluoroalkyl Substances Elevate the Risk of Spontaneous Preterm Birth? A Nested Case-Control Study in China.

Previous animal and human studies suggest potential links between maternal exposure to per- and polyfluoroalkyl substances (PFASs) and adverse birth outcomes. As spontaneous preterm birth (SPB) represents a major cause of infant mortality and precursor to future morbidity, we conducted a prospective nested case-control study in Shanxi Province, China to investigate the association between prenatal PFAS exposure and SPB risk, as well as the associations with biomarkers of oxidative stress and systemic inflammation. Among 4229 women enrolled during 2009-2013, 144 SPB cases and 375 controls were included in this study. Seventeen PFASs, as well as monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and heme oxygenase-1 (HO-1), were measured in maternal plasma or serum collected during 4th-22nd gestational weeks. Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and its alternative chlorinated polyfluoroether sulfonic acid (6:2 Cl-PFESA) were detected in more than 90% samples with a median concentration of 0.79, 1.79, and 0.34 ng/mL, respectively. The analyses revealed no significant associations between plasma PFASs and the SPB risk after adjusting for potential confounders. However, concentrations of PFOS and 6:2 Cl-PFESA were both significantly and positively associated with MCP-1 levels, while PFOA was inversely associated with IL-8. Our findings suggested that maternal exposure to the determined low levels of PFAS did not induce an elevated risk of SPB, but the exposure may disturb potential biochemical pathways of inflammation. The latter has important implications for possible birth outcome effects and developmental effects in fetuses and newborns, which warrants close attention.

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation. METHODS: We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing. RESULTS: Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines. CONCLUSIONS: The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines.

PURPOSE: The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group. METHODS: A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results. RESULTS: Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy (P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index. CONCLUSION: New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population.

Diffuse large B cell lymphoma associated with chronic inflammation arising within atrial myxoma: aggressive histological features but indolent clinical behaviour.

AIMS: Primary cardiac lymphoma (PCL) is a rare neoplasm. PCL is fatal, unless it is diagnosed and treated early. Recently, a small number of cases of diffuse large B cell lymphoma (DLBCL) arising within atrial myxoma have been reported in immunocompetent patients and showed aggressive histological features but an indolent clinical behaviour. METHODS AND RESULTS: We present four unusual cases of Epstein-Barr virus (EBV)-positive DLBCL arising within atrial myxoma with detailed clinical, histological, immunophenotypical and genotypical features in immunocompetent patients, and review the literature for 11 similar cases. All the patients appeared to have morphological features of DLBCL, B lineage immunophenotype, high proliferative index and latency type III of EBV infection. They achieved complete tumour resection without chemotherapy or radiotherapy after surgery and were healthy at 3- and 7-month and 7- and 10-year follow-ups, respectively. CONCLUSIONS: We suggest that this lymphoma should be regarded as a unique DLBCL associated with chronic inflammation (DLBCL-CI) because of an indolent clinical behaviour to avoid excessive or unnecessary treatments. In addition, early accurate diagnosis and complete resection of this tumour are crucial for optimal patient outcome.

Intravoxel incoherent motion MRI for the differentiation of benign, intermediate, and malignant solid soft-tissue tumors.

PURPOSE: To determine the diagnostic potential of apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-derived parameters for the differentiation of benign, intermediate, and malignant solid soft-tissue tumors. MATERIALS AND METHODS: The Institutional Review Board approved this prospective study, and informed consent was obtained. IVIM imaging was performed in 64 patients including 44 benign, 6 intermediate, and 14 malignant solid soft-tissue tumors at 1.5T. The IVIM parameters of the soft-tissue tumors were assessed using the Kruskal-Wallis test. The diagnostic performance of the parameters was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The ADC and true diffusion coefficient (D) values of malignancies (1.28 ± 0.31, 1.06 ± 0.23 [×10-3 mm2 /sec]) were significantly lower than those of intermediate (1.49 ± 0.54, 1.30 ± 0.50 [×10-3 mm2 /sec]), or benign soft-tissue tumors (1.62 ± 0.37, 1.36 ± 0.33 [×10-3 mm2 /sec]) (P = 0.007 and P = 0.009, respectively). In the differential diagnosis of malignancies from benign tumors, ADC demonstrated the highest area under the curve (Az) value (Az = 0.793). The perfusion fraction (f) values of intermediate soft-tissue tumors (8.41 ± 2.73) were significantly different from those of benign and malignant tumors (14.70 ± 5.37 [P = 0.002]; 14.44 ± 5.31 [P = 0.021]). f showed the highest Az value in differentiating intermediate from benign, and malignant soft-tissue tumors (Az = 0.90, and Az = 0.833, respectively). The pseudodiffusion coefficient (D*) values of malignant soft-tissue tumors (144.40 ± 24.88 [×10-3 mm2 /sec]) were significantly higher than those of benign tumors (124.96 ± 26.24 [×10-3 mm2 /sec]) (P = 0.019). CONCLUSION: IVIM imaging may be helpful for differentiating benign, intermediate, and malignant solid soft-tissue tumors. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1611-1618.

[Detection of KRAS,NRAS and BRAF gene mutations in colorectal carcinoma].

OBJECTIVE: To investigate mutations frequencies of KRAS,NRAS and BRAF genes in colorectal carcinoma. METHODS: Tissue specimens from 200 colorectal cancer patients at diagnosis were collected and subject to KRAS,NRAS and BRAF mutation analyses by PCR-based direct DNA sequencing targeting exons 2, 3 and 4 of KRAS gene, exons 2, 3 and 4 of NRAS gene and exon 15 of BRAF gene. RESULTS: Activating mutations were detected in KRAS (44%, 88/200), NRAS (2%, 4/200) and BRAF (5%, 10/200) in this study cohort.Among KRAS mutations, 64.8% (57/88) occurred in codon 12 and 12.5% (11/88) occurred in codon 13. KRAS gene mutation in exon 3 mainly involved codons 59 and 61. KRAS gene mutation in exon 4 mainly involved codons 117 and 146. CONCLUSIONS: Mutations at exon 2 of KRAS gene have the highest frequency in colorectal carcinoma. Expanding the detection sites of KRAS gene combined with NRAS and BRAF genes may help to identify patients who will most likely benefit from targeted therapies.

[Clinicopathologic analysis of HIV-negative plasmablastic lymphoma].

OBJECTIVE: To study the clinical, pathologic, immunophenotype, molecular characteristics and prognosis of HIV-negative plasmablastic lymphoma (PBL). METHODS: Twelve cases of HIV-negative PBLs diagnosed between 2005 and 2014 in Guangdong General Hospital were identified according to WHO classification of tumors of haematopoietic and lymphoid tissues (2008). The clinicopathologic features and outcome were analyzed and the relevant literatures were reviewed. RESULTS: The patients were predominantly male (11/12) with a median age of 55.5 years. The tumor cells showed the characteristic combination of immunoblastic/plasmablastic morphology, plasma cell phenotype and high proliferation, no expression of mature B cell markers. 7/10 of the cases were EBER positive. Two cases were positive for C-myc translocation. Four of twelve patients were died. CONCLUSIONS: PBL is a rare, aggressive B-cell lymphoma. HIV-negative PBL has lower rate of oral involvement and EBER expression than HIV-positive patients, the differential diagnosis is very challenging, and the prognosis is worse.

Single-cell RNA sequencing reveals heterogeneity and differential expression of the maternal-fetal interface during ICP and normal pregnancy.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) can cause adverse perinatal outcomes. Previous studies have demonstrated that the placenta of an ICP pregnancy differs in morphology and gene expression from the placenta of a normal pregnancy. To date, however, the genetic mechanism by which ICP affects the placenta is poorly understood. Therefore, the aim of this study was to investigate the differences in main cell types, gene signatures, cell ratio, and functional changes in the placenta between ICP and normal pregnancy. METHODS: Single-cell RNA sequencing (scRNA-seq) technology was used to detect the gene expression of all cells at the placental maternal-fetal interface. Two individuals were analyzed - one with ICP and one without ICP. The classification of cell types was determined by a graph-based clustering algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the R software phyper () function and DAVID website. The differentially expressed genes (DEGs) encoding transcription factors (TFs) were identified using getorf and DIAMOND software. RESULTS: We identified 14 cell types and 22 distinct cell subtypes that showed unique functional properties. Additionally, we found differences in the proportions of fibroblasts 1, helper T (Th) cells, extravillous trophoblasts, and villous cytotrophoblasts, and we observed heterogeneity of gene expression between ICP and control placentas. Furthermore, we identified 263 DEGs that belonged to TF families, including zf-C2H2, HMGI/HMGY, and Homeobox. In addition, 28 imprinted genes were preferentially expressed in specific cell types, such as PEG3 and PEG10 in trophoblasts as well as DLK1 and DIO3 in fibroblasts. CONCLUSIONS: Our results revealed the differences in cell-type ratios, gene expression, and functional changes between ICP and normal placentas, and heterogeneity was found among cell subgroups. Hence, the imbalance of various cell types affects placental activity to varying degrees, indicating the complexity of the cell networks that form the placental tissue system, and this alteration of placental function is associated with adverse events in the perinatal period.

Genomics and tumor microenvironment of breast mucoepidermoid carcinoma based on whole-exome and RNA sequencing.

Mammary mucoepidermoid carcinoma (MEC) is a rare entity. The molecular characteristics of breast MEC have not been fully investigated due to its rarity. We performed a retrospective study among 1000 patients with breast carcinomas and identified four cases of breast MEC. Clinical and demographic data were collected. Immunohistochemistry panels which were used to diagnose salivary gland MEC and breast carcinomas were also performed. MAML2 rearrangements were detected by FISH and fusion partners were identified by RNA sequencing. Whole-exome sequencing (WES) was used to reveal the genomes of these four breast MEC. Then, the biological functions and features of breast MEC were further compared with those of invasive breast carcinomas and salivary gland MEC.According to Ellis and Auclair's methods, these four breast MEC could be classified as low-grade breast MEC. All the patients were alive, and disease-free survival (PFS) ranged from 20 months to 67 months. Among these four breast MEC, two cases were triple-negative, and the other two cases were found to be ER positive, with one also showing HER2 equivocal by immunohistochemical staining, but no amplification in FISH. FISH analysis confirmed the presence of the MAML2 translocation in three of four tumors, and CRTC1-MAML2 fusion was confirmed in two of them by RNA-sequencing. The average coverage size of WES for the tumor mutation burden estimation was 32 Mb. MUC4, RP1L1 and QRICH2 mutations were identified in at least three tumors, and these mutation also existed in breast invasive carcinoma databases (TCGA, Cell 2015; TCGA, Nature 2012). The results showed that there were many genes in breast MEC overlapping with the breast invasive carcinoma databases mentioned above, range from 5 to 63 genes (median:21 genes). Next, we assessed immune cell infiltration levels in these tumors. In all these tumors, M2 macrophages and plasma cell were in the high infiltration group. Our breast MEC showed different results from the salivary gland MEC, whose plasma cells were in the low infiltration group. Overall, we first analyzed the genomics and tumor microenvironment of breast mucoepidermoid carcinoma and proposed our hypothesis that although MECs arising in the breast resemble their salivary gland counterparts phenotypically, our findings indicate that breast MECs probably resemble invasive breast carcinomas at the genetic level and immune cell infiltration levels. More cases and in deep research need to be done to further understand this rare carcinoma.

Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy.

The purpose of this study was to investigate the correlation between tau expression in primary breast cancer and sensitivity to taxanes during neoadjuvant chemotherapy in patients with breast cancer. We used immunohistochemistry to examine tau expression in breast cancer biopsies from 113 primary breast cancer patients and evaluated the correlation between tau expression and taxane sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR, five (12.5 %) were positive for tau expression. In univariate analysis, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and tau were found to be significantly predictive of a pCR (P = 0.001, 0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant for pCR on multivariate analysis (P = 0.025, 0.005, and 0.043, respectively). Tau expression was positively related to ER (P = 0.007) and progestin receptor (P = 0.008). In conclusion, tau protein expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau expression were more likely to achieve pCR.

[B-cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations].

OBJECTIVE: To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit" lymphoma). METHODS: Tissue microarray was constructed from formalin-fixed and paraffin-embedded tissue samples of aggressive B cell lymphomas diagnosed between 2009 and 2012, including 129 cases of diffuse large B cell lymphoma (DLBCL), 5 cases of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU), 7 cases of Burkitt lymphoma and 4 cases of high-grade follicular lymphoma with diffuse large B cell lymphoma component. Interphase fluorescence in-situ hybridization (FISH) was performed with a panel of probes including myc, bcl-2/IgH and bcl-6 to document related gene translocation and copy number changes. Medical record review was performed and follow-up data was recorded. RESULTS: Among 145 cases, 5 cases (3.4%) of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 rearrangements (double-hit lymphomas) were identified, including 2 cases involving myc and bcl-2 translocations (1 DLBCL and 1 BCLU), and 3 cases involving myc and bcl-6 translocations (all DLBCLs). Three cases with concurrent bcl-2/IgH and bcl-6 translocations were found. Single gene translocations or increase of copy numbers were found in 66 cases, representing 51.2% (66/129) of all de novo DLBCLs. Ki-67 index of the 5 "double-hit" lymphomas ranged from 60% to 100%. Clinical follow-up data were available in 4 of the 5 "double-hit" lymphoma patients, three of whom died within 2 years and 1 patient was alive after 36 months of follow-up. CONCLUSIONS: "Double-hit" B-cell lymphomas are rare and can only be identified by molecular detection. They should not be considered synonymous with BCLU morphologically, and may present entities within other morphological spectra. Most of the patients have a poor prognosis. Further in-depth studies of larger case numbers are required to determine the pathologic and genetic variables of the lesion.

MRI findings of benign tumors and tumor-like diseases of the tongue with radiologic-pathologic correlation.

Benign tumors or tumor-like lesions of the tongue are uncommon lesions that comprise a heterogeneous group of neoplasms. Although there are a variety of benign tumors or tumor-like lesions, the imaging appearance of these diseases is not well defined because of a paucity of scientific literature on this topic. Most benign tongue tumors usually appear as submucosal bulges located in the deep portion of the tongue. Their true features and extent may only be identified on cross-sectional images such as CT and MRI. Thus, CT and MRI play an important role in the diagnosis of these unusual lesions. It is important that radiologists be able to identify the characteristic CT and MR imaging features that can be used to narrow the differential diagnosis with increased diagnostic confidence, suggest specific histologic tumor types. In this pictorial essay, we provide insights into the MRI presentations of benign tongue tumors and tumor-like diseases and their radiologic-pathologic correlation. Benign tumors or tumor-like lesions of the tongue described herein include papilloma, lipoma, hemangioma, venous malformations, schwannoma, neurofibroma, epidermoid cyst, and dermoid cyst.

Bimetallic palladium-copper nanoplates with optimized d-band center simultaneously boost oxygen reduction activity and methanol tolerance.

The methanol-poisoning of electrocatalysts at the cathodic part of direct methanol fuel cells (DMFCs) can severely degrade the overall efficiency. Therefore, engineering cathodic catalysts with outstanding oxygen reduction activity, and simultaneously, superior methanol tolerance is greatly desired. Herein, bimetallic palladium-copper (PdCu) nanoplates with the optimized d-band center are designed as promising cathodic catalysts for DMFCs. It shows outstanding oxygen reduction activity with a mass activity (MA) of 0.522 A mgPd-1 in alkaline electrolyte, overwhelming the benchmarked commercial Pt/C and Pd/C. Meanwhile, it has prominent stability with only 4.0 % loss in MA after continuous 20 K cycles. More importantly, the PdCu nanoplates are almost inert toward methanol oxidation and show excellent anti-methanol capability. The theoretical calculations reveal that the downshift of d-band center in PdCu nanoplates and the electronic interaction between Pd and Cu atoms could effectively lower the methanol adsorption energy, thus leading to enhanced methanol tolerance. This work highlights the important role of tuning the electronic structure and optimized geometry of electrocatalysts to simultaneously boost their oxygen reduction activity, stability, and methanol tolerance for their future application in DMFCs.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

BACKGROUND: Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. METHODS: A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. RESULTS: The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). CONCLUSION: A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

The correlation analysis of TERT promoter mutations with IDH1/2 mutations and 1p/19q detected in human gliomas.

BACKGROUND: To investigate the correlations between mutations in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase (IDH) 1 and 2 mutations or 1p/19q deletion in human gliomas. METHODS: TERT promoter gene and IDH gene mutations in 110 glioma specimens were evaluated using first generation Sanger sequencing. The 1p/19q status was determined with fluorescence in situ hybridization. The relationship between TERT promoter mutations and IDH gene mutations as well as 1p/19q deletion was analyzed using the χ2 test and Spearman rank correlation test. RESULTS: The TERT promoter mutation rate in 110 glioma specimens was 39.09% (43/110), with a rate of 32.56% (14/43) for C228T mutation and 67.44% (29/43) for C250T mutation. The IDH gene mutation rate in all specimens was 31.82% (35/110), with a rate of 52.78% (19/36) in low-grade gliomas and 21.62% (16/74) in high grade gliomas. The 1p/19q deletion rate was 28.18% (31/110) in all specimens. Correlation analysis revealed that TERT promoter mutation was positively correlated with 1p/19q deletion (relative precision (rp) = 0.244, P = .015). In lower-grade glioma with IDH mutation, TERT promoter mutation was positively correlated with 1p/19q deletion (rp = 0.856, P = .000). The prognosis for gliomas with IDH mutation/TERT mutation/1p/19qdeletion was good. Mutation of the TERT promoter was negatively correlated with IDH gene mutation (rp = -0.290, P = .004), except in 10 cases of oligodendroglioma and 1 case of anaplastic oligodendroglioma. CONCLUSION: There may be a complex inter-regulatory relationship between the mutations of the TERT promoter and IDH gene as well as 1p/19q abnormalities in human gliomas.

Digital twin key technology on rare earth process.

Digital twin can be defined as a digital equivalent of an object of which it can mirror its behavior and status or virtual replicas of real physical entities in Cyberspace. To an extent, it also can simulate and predict the states of equipment or systems through smart algorithms and massive data. Hence, the digital twin is emerging used in intelligent manufacturing Systems in real-time and predicting system failure and also has introduced into a variety of traditional industries such as construction, Agriculture. Rare earth production is a typical process industry, and its Extraction Process enjoys the top priority in the industry. However, the extraction process is usually characterized by nonlinear behavior, large time delays, and strong coupling of various process variables. In case of failures happened in the process, the whole line would be shut down. Therefore, the digital twin is introduced into the design of process simulation to promote the efficiency and intelligent level of the Extraction Process. This paper proposes the techniques to build the rare earth digital twin such as soft measurement of component content, component content process simulation, control optimization strategy, and virtual workshop, etc. At the end, the validity of the model is verified, and a case study is conducted to verify the feasibility of the whole Digital twin framework.