High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal canrcinoma after radiotherapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of epithelial carcinoma that is common in East and Southeast Asia. Distant metastasis after radiotherapy remains the main cause of treatment failure and preradiotherapy immune system function can influence prognosis. Our study aimed to identify immune-related prognostic factors for NPC after radiotherapy and establish a prognostic model to predict progression-free survival (PFS) and distant metastasis-free survival (DMFS). METHODS: We enrolled NPC patients and divided them into training and validation cohorts with follow-up. We collected clinical information and investigated immune cells, EBV DNA and cytokines in the peripheral blood of NPC patients before radiotherapy and EBV DNA after radiotherapy. Among these immune cells, we included CD8+CD28- T cells, which are a unique T-cell immunosenescent subset that increases in human peripheral blood with increasing age and declining immune function. Based on the detection results and clinical information, we utilized Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen the PFS and DMFS prognostic factors and build nomograms to predict the PFS and DMFS of NPC. We also verified the results in the validation set. RESULTS: Three factors associated with PFS were selected: proportion of CD8+CD28- T cells posttreatment EBV and N stage. Three factors associated with DMFS were screened: proportion of CD8+CD28- T cells, posttreatment EBV and N stage. CD8+CD28- T cells are correlated with systemic inflammation and posttreatment immunosuppression. The C-indexes were 0.735 and 0.745 in the training and validation cohorts for predicting PFS. For DMFS, the C-indexes were 0.793 and 0.774 in the training and validation cohorts. CONCLUSIONS: The pretreatment proportion of CD8+CD28- T cells is a candidate prognostic biomarker for NPC after radiotherapy. The constructed nomogram models based on CD8+CD28- T cells have good predictive value.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae related urinary tract infection in adult cancer patients: a multicenter retrospective study, 2015-2019.

BACKGROUND: The aim of this study was to investigate the prevalence and risk factors of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae related urinary tract infections (UTI) in adult cancer patients. METHODS: We conducted a retrospective study of three cancer hospitals centered on Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2019. The clinical characters, risk factors and antimicrobial susceptibility of ESBL-producing Enterobacteriaceae UTI in adult cancer patients were described and analyzed. RESULTS: A total of 4967 specimens of UTI were evaluated, of which 909 were positive. After excluding multiple infection bacteria, non-conforming strains, inconsistent pathological information, no drug sensitivity test or medical records, 358 episodes remained. Among them, 160 episodes belonged to ESBL-producing Enterobacteriaceae, while 198 were classified into non-ESBL group. The prevalence of ESBL UTI circled around 39.73 to 53.03% for 5 years. Subgroup analysis by tumor type revealed that 62.5% of isolates from patients with urological tumors were ESBL positive. Multivariate analysis showed that tumor metastasis (OR 3.41, 95%CI 1.84-6.30), urological cancer (OR 2.96, 95%CI 1.34-6.53), indwelling catheter (OR 2.08, 95%CI 1.22-3.55) and surgery or invasive manipulation (OR 1.98, 95%CI 1.13-3.50) were the independent risk factors. According to antimicrobial sensitivity, meropenem, imipenem and piperacillin/tazobactam were the most commonly used antibiotics for ESBL-producing Enterobacteriaceae UTI. CONCLUSIONS: In view of the high prevalence, clinicians should be alert to the occurrence of ESBL UTI, especially for patients with urological cancer or metastatic tumors. Regular replacement of urinary catheters, reduction of unnecessary invasive operations and selection of appropriate antibiotics are the necessary conditions to deal with the occurrence of ESBL UTI in adult cancer patients.

LncRNA MIR155HG Overexpression Promotes Proliferation, Migration, and Chemoresistance in Gastric Cancer Cells.

Long non-coding RNAs are thought to play a vital role in a variety of human malignancies. Studies have shown that MIR155 host gene (MIR155HG) acts as an oncogene in several cancers, but the function and its mechanism of MIR155HG in gastric cancer (GC) is still poorly understood. In this study, we determined the biological functions and underlying mechanisms of MIR155HG in GC cells. We found that expression levels of MIR155HG was increased markedly in GC patients' serum. In vitro and in vivo studies demonstrated that MIR155HG modulated the malignant phenotype of GC cells, such as cell proliferation, colony forming ability, cell migration ability, and tumor growth in nude mice. Next, our results revealed that NF-κB and STAT3 signaling pathways could be involved in regulating the malignant behavior of GC cells. Our rescue experiments showed that inhibiting NF-κB and STAT3 signaling pathways attenuated the phenotypes caused by MIR155HG overexpression. Moreover, cytotoxicity and apoptosis assays revealed overexpression of MIR155HG reduced the apotosis of GC cells induced by cisplatin and 5-FU. Together, our studies suggested that MIR155HG overexpression promoted proliferation, migration, and chemoresistance of GC cells. These results might provide a lncRNA-based target for GC treatment in future.

Investigation on reliability of red micro-light emitting diodes with atomic layer deposition passivation layers.

In this study, AlGaInP red light emitting diodes with sizes ranging from 5 to 50 micrometers were fabricated and characterized. The atomic layer deposition technology is applied to coat a layer of silicon dioxide for passivation and protection. The top emission area is covered by ITO layer to maximize the optical output. From the optical measurement, the linewidth and emission peaks shift very little among different current levels (from 30 to 150 A/cm2). High current level lifetests are performed and a 15 µm ALD device can last 27 hours of continuous operation at 100 A/cm2 before their diode junction failed. A much shorter lifetime of 5.32 hours was obtained when the driving current is raised to 400 A/cm2. When the same condition was applied to 15 µm PECVD devices, 25 hours and 4.33 hours are registered for 100 A/cm2 and 400 A/cm2 tests, respectively. The cross-sectional SEM reveals the voids, defects, and dark lines developed during the aging tests, and most of them are caused by top contact failure. The surface layers of ITO and SiO2 were melted and the dark lines which were originated from the top surface propagated through the device and led to the eventual failure of the diode. The optical intensity degradation slopes of different sizes of devices indicate a large device can last longer in this accelerated aging test. The efficiencies of the devices are also evaluated by the ABC model and the fitted bimolecular coefficient ranges from 1.35 to 3.40×10-10 cm3/s.

Evaluation of the SureX HPV genotyping test for the detection of high-risk HPV in cervical cancer screening.

BACKGROUND: The SureX HPV genotyping test (SureX HPV test), which targets the human papillomavirus (HPV) E6/E7 genes was compared with the Cobas 4800 and Venus HPV tests for detecting 14 high-risk HPV (HR-HPV) types in clinical referral and follow-up patients to evaluate its value for cervical cancer screening. METHODS: Two different populations were enrolled in the study. The first population comprised 185 cases and was used for comparing the SureX HPV test (Health, China) with the Cobas 4800 test (Roche, USA). The second population comprised 290 cases and was used for comparing the SureX HPV test (Health, China) with the Venus HPV test (Zhijiang, China). Polymerase chain reaction (PCR) sequencing was performed for further confirmation of discordant results. RESULTS: In the first population, the overall agreement rate was 95.6% for 14 high-risk HPV types. Eight discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 75.0% between the SureX HPV test and PCR sequencing and 25.0% between the Cobas 4800 test and PCR sequencing (P < 0.01). In the second population, the overall agreement rate was 95.5%. Thirteen discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 76.9% between the SureX HPV test and PCR sequencing and 23.1% between the Venus HPV test and PCR sequencing (P < 0.01). With cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the sensitivity values of the SureX HPV test and the Venus HPV test were 93.5% and 92.0%, (P > 0.05), while the specificity values were 43.3% and 46.7%, respectively (P > 0.05). CONCLUSION: The SureX HPV test had good consistency with both the Cobas 4800 and Venus HPV tests for 14 HR-HPV types. In addition, it avoided some false negatives and false positives. Therefore, the SureX HPV test can be used for cervical cancer screening.

A Panel of Serum Noncoding RNAs for the Diagnosis and Monitoring of Response to Therapy in Patients with Breast Cancer.

BACKGROUND The aim of this study was to identify a panel of serum noncoding RNAs (ncRNAs) as potential diagnostic and prognostic biomarkers for breast cancer. MATERIAL AND METHODS Patients with breast cancer (n=30), and normal controls (n=30) were included in the 'training set.' A 'validation set' included cases of breast cancer (n=128) and controls (n=77). All cases provided blood samples for serum analysis. All cases of breast cancer were confirmed histologically and were staged. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of 11 candidate ncRNAs, including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), in the serum. The expression of the panel of ncRNAs was further analyzed following surgery or chemotherapy. RESULTS The four ncRNAs identified in the serum of patients with breast cancer included let-7a, miR-155, miR-574-5p, and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Analysis based on the risk score showed that the panel of these four ncRNAs could effectively distinguish between patients with breast cancer and the control group. For the training set and the validation set, analysis of the receiver-operating characteristic (ROC) curve showed that the areas under the curve (AUCs) were 0.960 and 0.968, respectively. Also, the serum expression levels of the four ncRNAs differed in the pre-treatment and the post-treatment patients with breast cancer, with levels of miR-155 showing a significant decrease following chemotherapy. CONCLUSIONS A panel of serum ncRNAs, including let-7a, miR-155, miR-574-5p, and MALAT1, was shown to be present in patients with breast cancer.

Overexpression of the Ubiquilin-4 (UBQLN4) is Associated with Cell Cycle Arrest and Apoptosis in Human Normal Gastric Epithelial Cell Lines GES-1 Cells by Activation of the ERK Signaling Pathway.

BACKGROUND Ubiquilin-4 (UBQLN4) is a component of the ubiquitin-proteasome system and regulates the degradation of many proteins implicated in pathological conditions. The aim of this study was to determine the role of UBQLN4 in regulating the proliferation and survival of the normal gastric epithelial cell line GES-1. MATERIAL AND METHODS We constructed GES-1 lines stably overexpressing UBQLN4 by lentiviral infection. Cell proliferation, apoptosis, and the cell cycle were analyzed using the MTT assay and flow cytometric assays. Phosphorylation of ERK, JNK, p38, and expression of cyclin D1 were detected by western blot analysis. RESULTS Overexpression of UBQLN4 significantly reduced proliferation and induced G2/M phase arrest and apoptosis in GES-1 cells. Moreover, upregulation of UBQLN4 increased the expression of cyclin D1 and phosphorylated ERK, but not JNK or p38. CONCLUSIONS These data suggest that UBQLN4 may induce cell cycle arrest and apoptosis via activation of the ERK pathway and upregulation of cyclin D1 in GES-1 cells.

Decreased expression of LncRNA SLC25A25-AS1 promotes proliferation, chemoresistance, and EMT in colorectal cancer cells.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in colorectal cancer (CRC); however, only few CRC-related lncRNAs have been characterized. In this study, we aimed to dig out potential dysregulated lncRNAs that are highly involved in CRC development. Using a lncRNA-mining approach, we performed lncRNA expression profiling in a large CRC cohort from Gene Expression Ominus (GEO), GSE39582 test series (N = 585). We identified 31 downregulated lncRNAs and 16 upregulated lncRNAs from the GSE39582 test series patients (566 tumor patients and 19 normal controls). The reliability of lncRNA expression profiles was further confirmed by RT-qPCR in carcinoma tissues and paired adjacent normal tissues from 30 CRC patients, also in the serum from 109 CRC patients, and 99 normal individuals. We demonstrated that the expression of SLC25A25-AS1, which has not been reported previously, was significantly decreased in both the tumor tissues (27 out of 30) and serum of CRC patients. SLC25A25-AS1 overexpression significantly inhibited proliferation and colony formation in colorectal cancer cell lines, and downregulation of SLC25A25-AS1 obviously enhanced chemoresistance and promoted EMT process in vitro associated with Erk and p38 signaling pathway activation. Therefore, SLC25A25-AS1 was determined to play a tumor suppressive role in CRC. Our results might provide a lncRNA-based target for CRC treatment.

Serum microRNA expression profile as a diagnostic panel for gastric cancer.

PURPOSE: Previously, we identified six miRNAs that are differentially expressed in colorectal cancer compared with healthy controls. Here, we tested them in gastric cancer GC. METHODS: We performed quantitative RT-PCR on serum samples from 92 patients with gastric cancer and 89 controls for the six miRNAs, and analyzed their risk scores to evaluate the diagnostic value of the serum miRNA profiling system. RESULTS: After a two-phase selection and validation process, five miRNAs were found to significantly differ in expression between gastric cancer samples and control samples, including miR-21, miR-31, miR-92a, miR-181b, and miR-203. Risk score analysis showed that this miRNA panel could distinguish gastric cancer cases from controls with high sensitivity and specificity. Under receiver operating characteristic curves, areas under the curve for tumor identification were 0.933 (95% confidence interval [CI]: 0.86-1.007) for the training set and 0.919 (95% CI: 0.863-0.975) for the validation set-markedly higher than those of carcinoembryonic antigen (0.624) and carbohydrate antigen 19-9 (0.603). CONCLUSIONS: The signature of these five miRNAs is a novel and noninvasive biomarker for gastric cancer, and could facilitate and simplify its diagnosis.

The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways.

Ubiquitin C-terminal hydrolase-L1 (UCHL1) is a de-ubiquitinating enzyme, which enzymatic activity relies on the C90 site. The function of UCHL1 is controversial in different types of cancer, and its role in gastric cancer progression remains unclear. In this study, immunohistochemistry staining was applied to detect the expression of UCHL1 in primary gastric cancer and liver metastases from gastric cancer. MKN45 and BGC823 cell lines with stable expression of de-ubiquitinase active UCHL1 or inactive UCHL1-variant C90S were established by lentiviral infection. The effect of UCHL1 on cell proliferation was evaluated by MTT and colony formation assays. The abilities of cell migration and invasion were determined by transwell assay. Protein expression levels were determined by Western blot. The results indicated that UCHL1 had a significantly higher positive expression rate in liver metastases from gastric cancer compared with primary gastric cancer. Overexpression of UCHL1 in MKN45 and BGC823 cells promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity. UCHL1 activated Akt and Erk1/2, which process also required enzymatic activity and was necessary for mediating cell migration and invasion. These findings demonstrated that UCHL1 promoted cell proliferation, migration, and invasion depending on its de-ubiquitinase activity by activating Akt and Erk1/2, which may account for its higher positive expression rate in liver metastases from gastric cancer. UCHL1 could be a candidate biomarker and a therapeutic target for gastric cancer metastasis.

Study on the formation mechanism of blackening in damaged lotus rhizome epidermis: Effects of polyphenols and iron.

Lotus rhizome is an important aquatic vegetable, but the blackening of lotus rhizome epidermis (LRE) seriously affects its appearance and quality, which makes lotus rhizome products unmarketable. In this study, the effects of polyphenols and iron on the LRE color were studied to explore the possible mechanism of LRE blackening. Results indicated that the measurable total phenols contents in the mud treatment (MT) group were significantly reduced, and the total iron contents were significantly increased compared with the bruised treatment group (p < 0.05). The high-performance liquid chromatography results showed that the main polyphenols in LRE were dopa, gallocatechin, and catechin, as well as a small amount of catechol, epicatechin, proanthocyanidin B2, and proanthocyanidin C1. Moreover, the results of color difference and ultraviolet adsorption spectroscopy showed that there were obviously black or brown-gray of dopa (525 nm), gallocatechin (504.5 nm), and catechin (550 and 504.5 nm) with FeCl2. The simulated system treatment of LRE further confirmed that the chromaticity effect of dopa and iron in bruised LRE was similar to that of the MT group, whereas 1% (w/w) ascorbic acid, 2% (w/w) EDTA-2Na, or 3% (w/w) citric acid could solely prohibit the blackening. This suggested that the dopa in LRE and FeCl2 in mud may mainly combine into [2(DOPA-2H+)+Fe3+]- through non-covalent interaction, which leads to the blackening of bruised LRE under neutral conditions. These results can guide the storage of lotus rhizomes and improve the development of the lotus rhizome industry.

Knockdown of UBQLN1 Functions as a Strategy to Inhibit CRC Progression through the ERK-c-Myc Pathway.

PURPOSE: Colorectal cancer (CRC) is characterized by the absence of obvious symptoms in the early stage. Due to the high rate of late diagnosis of CRC patients, the mortality rate of CRC is higher than that of other malignant tumors. Accumulating evidence has demonstrated that UBQLN1 plays an important role in many biological processes. However, the role of UBQLN1 in CRC progression is still elusive. METHODS AND RESULTS: we found that UBQLN1 was significantly highly expressed in CRC tissues compared with normal tissues. Enhanced/reduced UBQLN1 promoted/inhibited CRC cell proliferation, colony formation, epithelial-mesenchymal transition (EMT) in vitro, and knockdown of UBQLN1 inhibited CRC cells' tumorigenesis and metastasis in nude mice in vivo. Moreover, the knockdown of UBQLN1 reduced the expression of c-Myc by downregulating the ERK-MAPK pathway. Furthermore, the elevation of c-Myc in UBQLN1-deficient cells rescued proliferation caused by UBQLN1 silencing. CONCLUSIONS: Knockdown of UBQLN1 inhibits the progression of CRC through the ERK-c-Myc pathway, which provides new insights into the mechanism of CRC progression. UBQLN1 may be a potential prognostic biomarker and therapeutic target of CRC.

Cross-Scale Fusion Transformer for Histopathological Image Classification.

Histopathological images provide the medical evidences to help the disease diagnosis. However, pathologists are not always available or are overloaded by work. Moreover, the variations of pathological images with respect to different organs, cell sizes and magnification factors lead to the difficulty of developing a general method to solve the histopathological image classification problems. To address these issues, we propose a novel cross-scale fusion (CSF) transformer which consists of the multiple field-of-view patch embedding module, the transformer encoders and the cross-fusion modules. Based on the proposed modules, the CSF transformer can effectively integrate patch embeddings of different field-of-views to learn cross-scale contextual correlations, which represent tissues and cells of different sizes and magnification factors, with less memory usage and computation compared with the state-of-the-art transformers. To verify the generalization ability of the CSF transformer, experiments are performed on four public datasets of different organs and magnification factors. The CSF transformer outperforms the state-of-the-art task specific methods, convolutional neural network-based methods and transformer-based methods. The source code will be available in our GitHub https://github.com/nchucvml/CSFT.

Central Compartment Atopic Disease and Its Surgical Outcomes: Olfactory Changes and Technical Notes.

Background: Central compartment atopic disease (CCAD) is a recent, novel phenotype of chronic rhinosinusitis. Only a few studies have assessed olfactory function in patients with CCAD. Objectives: We aimed to investigate olfactory function changes after functional endoscopic sinus surgery (FESS) in patients with CCAD and proposed some surgical techniques to enhance the postoperative olfactory outcomes in such patients. Design: A retrospective cohort study. Methods: We collected data from 23 patients (8 men and 15 women) with CCAD who underwent FESS performed by a surgeon in Taiwan, between June 2018 and December 2021. The demographic data, olfactory function, and serum and tissue eosinophil percentages of the included patients were analyzed. The Top International Biotech Smell Identification Test (TIBSIT; Top International Biotech, Taipei, Taiwan) was used to assess olfactory function. Results: Of the 23 patients, most (95%) showed a positive reaction to aeroallergens, and 2 patients (8.7%) had asthma. Ten patients (43.5%) had peripheral eosinophilia, and 9 (39%) had eosinophilic nasal polyps. Moreover, the patients presented with variable olfactory dysfunction; the mean preoperative TIBSIT (pr-TIBSIT) score was 12.8 ± 2.3 (range: 0-43), whereas the mean postoperative TIBSIT (po-TIBSIT) score was 29.2 ± 1.9 (range: 16-44). The po-TIBSIT score was significantly better than the pre-TIBSIT score (paired t test, P < .0001). The improvement in olfactory function was not significantly correlated with the patients' age, serum eosinophil percentages, and nasal polyp eosinophil counts. Conclusion: Our findings indicate that CCAD is significantly associated with olfactory dysfunction and that FESS can effectively improve olfactory function. To optimize postoperative olfactory outcomes, precise removal of polyps from the olfactory cleft without damaging the neuroepithelium is recommended. Our study provides valuable insights into the management of CCAD patients undergoing FESS and can guide surgical decision-making to achieve optimal olfactory function outcomes.

Severinia buxifolia-isolated acridones inhibit lung cancer invasion and decrease HIFα protein synthesis involving 5'UTR-mediated translation inhibition.

BACKGROUND: Lung cancer is one of the most common cancers worldwide and is by far the leading cause of cancer death attributed to its rapid metastasis and poor prognosis. Given that hypoxia-inducible factors (HIFs) are associated with cancer metastasis, discovering agents to inhibit HIF-mediated invasive cancer is highly desired. PURPOSE: This study aimed to investigate the natural acridone compounds isolated from Severinia buxifolia for the potential to delay hypoxia-induced lung cancer invasiveness by HIF inhibition. METHODS: Using a hypoxia-responsive element (HRE) luciferase reporter, cell migration and invasion assays, real-time PCR, Western blot, and DNA recombinant clones, compound effect on HIF activity, cancer metastasis, HIF-1α mRNA transcription, HIFs protein stability, and HIF-1α translation were observed under hypoxia conditions. RESULTS: Atalaphyllidine (Sbs-A) and atalaphyllinine (Sbs-B) were found to show the most potent effects on HIF transcriptional activity and HIF-1α protein expression in NSCLC cell line A549, although Sbs-A and Sbs-B might not attribute decreasing HIF-1α mRNA expression to potent inhibition of HIF activity. HIF-1α protein stability was not affected by Sbs-A; also, prolyl hydroxylase and proteasome inhibitors could not reverse the inhibitory effect from compounds. Furthermore, 3 - 10 µM low concentrations of Sbs-A inhibited HIF target gene expression, gelatin zymography activity, and A549 cancer invasion. Ultimately, Sbs-A inhibited HIF-1α 5'UTR-mediated translation independent of oxygen concentration, underlying the mechanism of compounds inhibiting HIF-1α protein expression. CONCLUSION: Our study proposed Severinia buxifolia-isolated acridone compounds inhibited 5'-mRNA HIFA-mediated translation and provided evidence supporting the ability of acridone compounds in targeting HIFα for delayed lung cancer metastasis.

Genomic bacterial load associated with bacterial genotypes and clinical characteristics in patients with scrub typhus in Hainan Island, Southern China.

Scrub typhus, caused by mite-borne Orientia tsutsugamushi (O. tsutsugamushi), is a major febrile disease in the Asia-Pacific region. The DNA load of O. tsutsugamushi in the blood was previously found to be significantly higher in patients with fatal disease than those with non-fatal disease and correlated with the duration of illness, presence of eschar, and hepatic enzyme levels. In this prospective observation study, we analyzed the association of bacterial DNA load with clinical features, disease severity, and genotype using real-time PCR targeting the 56 kDa TSA gene of O. tsutsugamushi in the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment. The median O. tsutsugamushi DNA load was 3.11×103 copies/mL (range, 44 to 3.3×106 copies/mL). The severity of patients was categorized as mild, moderate, and severe based on the number of dysfunctional organs, and no significant difference in O. tsutsugamushi DNA load was found among these groups. Patients infected with the Karp group showed a significantly higher O. tsutsugamushi DNA load than those in the Gilliam (P < 0.05) and TA763 (P < 0.01) groups. Patients belonging to the Li ethnic group showed a significantly higher DNA load than those in the Han ethnic groups. The blood bacterial DNA load of patients showed no significant difference between groups divided by gender, age, with or without eschar, or the season of disease onset. The highest body temperature recorded during fever onset was positively correlated with O. tsutsugamushi DNA load (ρ = 0.272, P = 0.022). Correlation analyses indicated that the serum total bilirubin level was positively correlated with O. tsutsugamushi DNA load. In conclusion, the findings in this study demonstrated the association of DNA load of O. tsutsugamushi with the severity and genotype in patients with scrub typhus in Hainan, China.

CheXGAT: A disease correlation-aware network for thorax disease diagnosis from chest X-ray images.

Chest X-ray (CXR) imaging is one of the most common diagnostic imaging techniques in clinical diagnosis and is usually used for radiological examinations to screen for thorax diseases. In this paper, we propose a novel computer-aided diagnosis (CAD) system based on a hybrid deep learning model composed of a convolutional neural network (CNN) and a graph neural network (GNN). The system is intended to explore implicit correlations between thorax diseases to aid in the multilabel chest X-ray image classification task, which we term ‶CheXGAT‶. Specifically, the proposed CheXGAT framework comprises two main modules: an image representation learning (IRL) module and a graph representation learning (GRL) module. We employ the IRL module to learn high-level visual representation features from the CXR image. From the GRL module, the self-attention mechanism aggregates neighborhood features from the graphic structure to enhance the implicit correlation between thorax diseases. We adopted a data-driven method to create a disease correlation matrix that works on the message passing and aggregation process for the nodes in the GRL module. After end-to-end training, the GRL module enhances the correlation between thorax diseases to improve diagnosis performance. We performed experiments on the NIH Chest X-ray14 dataset, which contains 112,120 frontal-view radiographs; each image has multiple thorax disease labels. In the experimental results, the average AUC score of our proposed CheXGAT model reached 0.8266, and the AUC scores of Emphysema and Hernia reached 0.9447 and 0.9313, respectively. In addition, we visualized explanations via a gradient-based localization method in our proposed CheXGAT framework. Compared with previous studies, the experimental results show the competitive performance of our framework. Specifically, we propose a CAD system that uses a hybrid model to help radiologists identify CXR images from 14 chest diseases for clinical diagnosis.

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis.

Background: Invasive lobular carcinoma (ILC) is more likely to have bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompanied by bone metastasis. Methods: We evaluated the women with bone-only metastasis of defined IDC or ILC reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson's χ2 test was used to compare the differences of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-specific survival (CSS). Results: Overall, 3,647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older and to have lower histological grade and a higher proportion of the HR*/HER2- subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, patients with ILC showed worse OS (median OS, 36 and 42 months, respectively, p < 0.001) and CSS (median CSS, 39 and 45 months, respectively, p < 0.001), especially in subgroups with HR*/HER2- subtype (OS, hazard ratio: 1.501, 95% CI 1.270-1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281-1.825, p < 0.001), lower histological grade (I-II) (OS, hazard ratio: 1.411, 95% CI 1.184-1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235-1.791, p < 0.001), or tumor burden, such as T0-2 (OS, hazard ratio: 1.693, 95% CI 1.368-2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405-2.205, p < 0.001) and N1-2 (OS, hazard ratio: 1.451, 95% CI 1.171-1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187-1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T3-4 and N3), triple-negative subtype, and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients. Conclusion: Patients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors, new targeted drugs, etc.

L1CAM expression in either metastatic brain lesion or peripheral blood is correlated with peripheral platelet count in patients with brain metastases from lung cancer.

Background: Systemic immune-inflammation states across the heterogeneous population of brain metastases from lung cancer are very important, especially in the context of complex brain-immune bidirectional communication. Previous studies from our team and others have shown that the L1 cell adhesion molecule (L1CAM) is deeply involved in the aggressive phenotype, immunosuppressive tumor microenvironment (TME), and metastasis during multiple malignancies, which may lead to an unfavorable outcome. However, little is known about the relationship between the L1CAM expression and the systemic immune-inflammation macroenvironment beyond the TME in brain metastases from lung cancer. Methods: Two cohorts of patients with brain metastases from lung cancer admitted to the National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, were studied in the present research. The L1CAM expression in cranial metastatic lesions by immunohistochemistry was explored in patients treated with neurosurgical resection, whereas the L1CAM expression in peripheral blood by ELISA was tested in patients treated with non-surgical antitumor management. Furthermore, based on peripheral blood cell counts in the CBC test, six systemic immune-inflammation biomarkers [neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio] were calculated. Then, the relationship between the L1CAM expression and these systemic immune-inflammation biomarkers was analyzed. In addition, these systemic immune-inflammation biomarkers were also used to compare the systemic immune-inflammation states in two cohorts of patients with brain metastases from lung cancer. Results: Positive L1CAM expressions in the metastatic brain lesions were accompanied with significantly increased peripheral platelet counts in patients treated with neurosurgical tumor resection (P < 0.05). Similarly, in patients treated with non-surgical antitumor management, L1CAM expressions in the peripheral blood were positively correlated with peripheral platelet counts (P < 0.05). In addition, patients prepared for neurosurgical tumor resection were presented with poorer systemic immune-inflammation states in comparison with the one with non-surgical antitumor management, which was characterized by a significant increase in peripheral neutrophil counts (P < 0.01), SII (P < 0.05), and NLR (P < 0.05) levels. Conclusion: The L1CAM expression in either the metastatic brain lesion or peripheral blood is positively correlated with the peripheral platelet count in patients with brain metastases from lung cancer. In addition, brain metastases that are prepared for neurosurgical tumor resection show poor systemic immune-inflammation states.