Characterization of sub-nanosecond pulse compression based on frequency-detuning SBS.

High-frequency, high-power picosecond lasers have important and wide-ranging applications in laser ranging, optoelectronic countermeasures, and ultrafine industrial processing. Pulse compression based on stimulated Brillouin scattering (SBS) can achieve a highly efficient picosecond laser output, while improving the peak power and beam quality of the laser. In this paper, a generator-amplifier two-cell structure with frequency-detuning was proposed to achieve a pulse output that combines high compression ratio and high energy reflectivity. The experiment proved that under a pump pulse width of 15 ns and repetition frequency of 10 Hz, when the generator cell and amplifier cell media were selected as HT-230, the highest energy reflectivity of 46% and narrowest compression pulse width of 1.1 ns were achieved, and the pulse compression ratio was 13.6. When the amplifier cell was selected as FC-770 and the generator cell was selected as HT-230, an energy reflectivity of 52% and a compression pulse width of 840 ps could be achieved simultaneously, and the pulse compression ratio was 18.

High-repetition-rate, quarter acoustic wave oscillation period pulse compression using transient stimulated Brillouin scattering.

In this work we demonstrate the compression of laser pulses at a high repetition rate, using transient stimulated Brillouin scattering (SBS). Output pulses with pulse durations close to the quarter-acoustic wave oscillation period (τf) was obtained. We find that the primary factors which limit the compression of pulses under high repetition-rate, transient conditions are the inherently low gain in the transient regime, thermal accumulation within the SBS medium and optical breakdown. We show that short phonon lifetimes can suppress the trailing edge amplification of the output pulse, while also reducing the threshold and improve energy efficiency. In this work, we demonstrate the generation of output laser pulses with a repetition-rate of 200 Hz and an average pulse duration of 1.08τf using the electronic-fluorinated liquid FC-43. Due to the fast decay of the acoustic field, compressed pulses with duration <τf were also observed. We also demonstrate efficient output of pulses with repetition-rate of 200 Hz and energy efficiency of up to 40% using the heat transfer fluid HT-230.

Tumor location as an indicator of survival in T1 resectable pancreatic ductal adenocarcinoma: a propensity score-matched analysis.

BACKGROUND: The latest 8th edition of the AJCC staging system emphasizes the importance of tumor size however, the clinical significance of the combination of tumor location with tumor size remains unknown. METHODS: We conducted this study to investigate the prognostic role of tumor location in T1 resectable pancreatic ductal adenocarcinoma (PDAC). Resectable PDAC patients from Surveillance, Epidemiology, and End Results (SEER) database (2004-2014) were selected for the propensity score matching analysis. We used matched cohort to analyze the relationship between clinicopathologic features and survival of patients. RESULT: Eight thousand, four hundred nine patients were included in the propensity score matching analysis and 4571 patients were selected for final analysis. In T1 patients, the patients with pancreatic head tumor had worse prognosis compared to the patients with body/tail tumors. Multivariate analysis result showed that pancreatic body/tail location was an independent indicator for better chances of survival in T1 PDAC patients (hazard ratio, 0.69; 95%CI, 0.52-0.93; P = 0.01). The modified staging system was more efficient than the AJCC 8th staging system. CONCLUSION: Modified staging system exhibited a good assessment of the survival rate. The tumor location is a good prognostic indicator for T1 resectable PDAC patients. Modification of T1 subgroup according to tumor location exhibited favorable survival prediction effects.

Intra-Ampullary Papillary-Tubular Neoplasm: A Population-Based Analysis.

BACKGROUND Intra-ampullary papillary-tubular neoplasm (IAPN) is recognized as a precancerous lesion with a great tendency to evolve into pancreatic cancer. The Surveillance, Epidemiology, and End Results (SEER) database is now large enough to study unusual cancers. Based on pathologic and epidemiologic characteristics of IAPN available in SEER, important clinicopathological correlations can be made. MATERIAL AND METHODS Cases of IAPN and other intraductal papillary mucinous neoplasms of the bile duct (OBIPMN) diagnosed between 1973 and 2014 were searched in the SEER database. The analysis was carried out with respect to patient clinical characteristics, tumor characteristics, incidence, and survival. RESULTS In total, 685 patients with IAPN were identified compared with 2465 patients with OBIPMN in the same period. The incidence rate of IAPN was decreased, with a 4.882% annual percent change. The patient characteristics of IAPN were quite different from OBIPMN in many characteristics, including age, gender, marital status, and survival. Compared with OBIPMN, the tumor characteristics of IAPN indicated that more patients were diagnosed at an earlier stage in multiple stage systems such as pathological grade (P<0.001), sixth American Joint Committee on Cancer stage (P<0.001), TNM stage (P<0.001), and SEER historic stage (P<0.001). In the survival analysis, the cancer-specific survival of IAPN was significantly better than OBIPMN (P<0.001) and the cancer-specific survival get worse at higher stages (P<0.001). Moreover, the 5-year cancer-specific survival rate of IAPN was also significantly better than that of OBIPMN (36.5% versus 25.4%, P<0.001). Finally, the multivariate analysis showed a correlation between cancer-specific survival and age of diagnosis and N stage (P<0.001). CONCLUSIONS Analysis of the SEER database clearly demonstrated that IAPN was a precancerous lesion tend to be diagnosed earlier compared with OBIPMN, which contributed to the better prognosis, and surgery was suggested if possible.

Prognostic value of progesterone receptor in solid pseudopapillary neoplasm of the pancreas: evaluation of a pooled case series.

BACKGROUND: The role of progesterone receptor (PR) has been reported in a series of pancreatic cysts. However, the relationship between PR and prognosis of solid pseudopapillary neoplasm of the pancreas (SPNP) has not been elucidated so far. The aim of our study was to evaluate the prognostic value of PR in SPNP. METHODS: A total of 76 patients with SPNP treated in our institution from January 2012 to December 2017 were included. Demographic parameters, laboratory data, pathologic information and clinical outcomes were analyzed by the use of survival analysis. In addition, a pooled case series was performed to evaluate the results. RESULTS: The institutional data included 76 patients (17 male and 59 female) ranging from 8 to 90 years (median, 30 years) in age. Kaplan-Meier survival analysis confirmed negative PR result was significantly associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) (both P < 0.001). In the pooled analysis, a total of 62 studies comprising 214 patients with SPNP were included. After multivariable cox analysis, negative PR result remained an independent prognostic factor for SPNP (DFS HR: 14.50, 95% CI: 1.98-106.05, P = 0.008; DSS HR: 9.15, 95% CI: 1.89-44.17, P = 0.006). CONCLUSION: Our results indicated the role of PR in predicting adverse outcome of patients with SPNP and negative PR result may serve as a potential prognostic factor.

T-Cell-Based Platform for Functional Screening of T-Cell Receptors Identified in Single-Cell RNA Sequencing Data Sets of Tumor-Infiltrating T-Cells.

The advent of single-cell RNA sequencing (scRNAseq) has enabled in-depth gene expression analysis of several thousand cells isolated from tissues. We recently reported the application of scRNAseq toward the dissection of the tumor-infiltrating T-cell repertoire in human pancreatic cancer samples. In this study, we demonstrated that combined whole transcriptome and T-cell receptor (TCR) sequencing provides an effective way to identify tumor-reactive TCR clonotypes on the basis of gene expression signatures. An important aspect in this respect was the experimental validation of TCR-mediated anti-tumor reactivity by means of an in vitro functional assay, which is the subject of the present protocol. This assay involves the transient transfection of mRNA gene constructs encoding TCRα/ß pairs into a well-defined human T-cell line, followed by co-cultivation with the tumor cells of interest and detection of T-cell activation by flow cytometry. Due to the high transfectability and the low background reactivity of the mock-transfected T-cell line to a wide variety of tumor cells, this assay offers a highly robust and versatile platform for the functional screening of large numbers of TCR clonotypes as identified in scRNAseq data sets. Whereas the assay was initially developed to test TCRs of human origin, it was more recently also applied successfully for the screening of TCRs of murine origin. Key features • Efficient functional screening of-and discrimination between-TCRs isolated from tumor-reactive vs. bystander T-cell clones. • Applicable to TCRs from CD8+ and CD4+ tumor-infiltrating T-cells originating from patient-derived tumor samples and syngeneic mouse tumor models. • Rapid flow cytometric detection of T-cell activation by means of TNFα and CD107a expression after a 5 h T-cell/tumor cell co-cultivation.

ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation.

Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention, but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP-signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As a proof-of-concept, we targeted the immune checkpoint protein, programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1. The R2PD1 chimeric protein binds to PD-L1 and at picomolar concentration induces its lysosomal degradation. In three melanoma cell lines, R2PD1 induced between 50 and 90% PD-L1 protein degradation. PD-L1 degradation was strictly dependent on ZNRF3/RNF43. Moreover, R2PD1 reactivates cytotoxic T cells and inhibits tumor cell proliferation more potently than Atezolizumab. We suggest that signaling-disabled ROTACs represent a paradigm to target cell surface proteins for degradation in a range of applications.

Transcriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8+ T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells. On the basis of a comprehensive dataset including 93 tumor-reactive and 65 bystander TCR clonotypes, we delineated a gene signature that effectively distinguishes between these T cell subsets in PDAC, as well as in other tumor indications. This revealed a high frequency of tumor-reactive TCR clonotypes in three genetically unstable samples. In contrast, the T cell repertoire in six genetically stable PDAC tumors was largely dominated by bystander T cells. Nevertheless, multiple tumor-reactive TCRs were successfully identified in each of these samples, thereby providing a perspective for personalized immunotherapy in this treatment-resistant indication.

Point Adversarial Self-Mining: A Simple Method for Facial Expression Recognition.

In this article, we propose a simple yet effective approach, called point adversarial self mining (PASM), to improve the recognition accuracy in facial expression recognition (FER). Unlike previous works focusing on designing specific architectures or loss functions to solve this problem, PASM boosts the network capability by simulating human learning processes: providing updated learning materials and guidance from more capable teachers. Specifically, to generate new learning materials, PASM leverages a point adversarial attack method and a trained teacher network to locate the most informative position related to the target task, generating harder learning samples to refine the network. The searched position is highly adaptive since it considers both the statistical information of each sample and the teacher network capability. Other than being provided new learning materials, the student network also receives guidance from the teacher network. After the student network finishes training, the student network changes its role and acts as a teacher, generating new learning materials and providing stronger guidance to train a better student network. The adaptive learning materials generation and teacher/student update can be conducted more than one time, improving the network capability iteratively. Extensive experimental results validate the efficacy of our method over the existing state of the arts for FER.

Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway.

BACKGROUND & AIMS: Accumulating evidence strongly suggests that hyperglycemia promotes the progression of pancreatic cancer (PC). Approximately 80% of patients with PC are intolerant to hyperglycemic conditions. In this study, we define the role of Bmi1, a stemness-related oncogene, in controlling the Warburg effect, and immune suppression under hyperglycemia conditions. METHODS: The diabetes mellitus model was established by intraperitoneal injection of streptozotocin. The role of the hyperglycemia-Bmi1-HK2 axis in glycolysis-related immunosuppression was examined in both orthotopic and xenograft in vivo models. Evaluation of immune infiltrates was carried out by flow cytometry. Human PC cell lines, SW1990, BxPC-3, and CFPAC-1, were used for mechanistic in vitro studies. RESULTS: Through bioinformatics analysis, we found that hyperglycemia was strongly related to aerobic glycolysis, immunosuppression, and cancer cell stemness. High glucose condition in the tumor microenvironment promotes immune suppression by upregulating glycolysis in PC cells, which can be rescued via knockdown Bmi1 expression or after 2-deoxy-D-glucose treatment. Through gain-/loss-of-function assessments, we found that Bmi1 upregulated the expression of UPF1, which enhanced the stability of HK2 mRNA and thereby increased the expression of HK2. The role of the hyperglycemia-Bmi-HK2 pathway in the inhibition of antitumor immunity was further verified via the immune-competent and immunodeficient mice model. We also demonstrated that hyperglycemia promotes the expression of Bmi1 by elevating the intracellular acetyl-CoA levels and histone H4 acetylation levels. CONCLUSIONS: Our results suggest that the previously unreported Bmi1-UPF1-HK2 pathway contributes to PC progression and immunosuppression, which may bring in new targets for developing effective therapies to treat patients with PC.

Discovery of a Series of 5-Amide-1H-pyrazole-3-carboxyl Derivatives as Potent P2Y14R Antagonists with Anti-Inflammatory Characters.

UDPG/P2Y14R signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2Y14R antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds. The optimized compound 16 (1-(4-fluorobenzyl)-5-(4-methylbenzamido)-1H-pyrazole-3-carboxylic acid, P2Y14R IC50 = 1.93 nM) showed strong binding ability to P2Y14R, high selectivity, notably improved solubility, and more favorable pharmacokinetic profiles. Moreover, compound 16 possessed extremely low cytotoxicity and anti-inflammatory effect in vitro. In an acute peritonitis model, compound 16 could effectively reduce the levels of inflammatory factor IL-6, IL-1ß, and TNF-α of mice induced by LPS. Compound 16, with potent in vitro and in vivo efficacy and favorable druggability, can be a promising candidate for further research.

Design, synthesis and evaluation of 3-amide-5-aryl benzoic acid derivatives as novel P2Y14R antagonists with potential high efficiency against acute gouty arthritis.

P2Y14 nucleotide receptor plays important roles in series of physiological and pathologic events especially associated with immune and inflammation. Based on the 3-amide benzoic acid scaffold reported by our group previously, a series of 5-aryl-3-amide benzoic acid derivatives were designed as novel P2Y14 antagonists with improved pharmacokinetic properties. Among which compound 11m showed most potent P2Y14 antagonizing activity with an IC50 value of 2.18 nM, furnishing greatly improved water solubility and bioavailability compared with PPTN. In MSU-induced acute gouty arthritis model in mice, 11m exerted promising in vivo efficacy in alleviating mice paw swelling and inflammatory infiltration. Mechanistically, compound 11m notably blocked pyroptosis of macrophages through inhibiting NLRP3 inflammasome activation. This work may contribute to the identification of potential therapeutic agents to intervene in acute gouty arthritis.

Using ESTIMATE algorithm to establish an 8-mRNA signature prognosis prediction system and identify immunocyte infiltration-related genes in Pancreatic adenocarcinoma.

OBJECTIVE: The tumour microenvironment is one of the significant factors driving the carcinogenesis of Pancreatic adenocarcinoma (PAAD). However, the underlying mechanism of how the tumour microenvironment impacts the prognosis of PAAD is not completely clear. RESULTS: The transcriptome and clinical data of 182 PAAD program cases were downloaded from the TCGA database. Three hundred thirty-three differentially expressed genes (DEGs) between high and low stromal groups and 314 DEGs between high and low immune score groups were identified using ESTIMATE score. Based on the 203 genes differentially expressed simultaneously in two score-related comparisons, we established an 8-mRNA signature to evaluate the prognosis of PAAD patients. Kaplan-Meier curves showed significantly worse survival for patients with high-risk scores in both the training and validation groups. The risk score was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. By searching the TCGA database, we showed that CA9, CXCL9, and GIMAP7 from the 8-mRNA signature were associated with the infiltration levels of immunocytes by regulating FOXO1 expression in PAAD. CONCLUSIONS: Unlike traditional methods of screening for differential genes in cancer and healthy tissues, we constructed a novel 8-mRNA signature to predict the prognosis of PAAD patients by applying ESTIMATE scoring to RNA-seq-based transcriptome data. Most importantly, we identified CA9, CXCL9, and GIMAP7 from the above eight genes as regulators of immunocyte infiltration by adjusting the expression of FOXO1 in PAAD. Thus, CA9, CXCL9, and GIMAP7 might be the ideal targets of immune therapy of PAAD. METHODS: ESTIMATE scoring was used to determine the stromal and immune scores of transcriptome datasets downloaded from the TCGA database. An mRNA-based prognostic signature was built for the training cohort via the LASSO Cox regression model. The signature was verified using a validation cohort. Kaplan-Meier curves and log-rank analysis were used to identify survival differences. Western blot analysis and RT-qPCR analysis were carried out to analyze the expression of specific proteins and mRNAs. IHC was performed to assess the protein levels of Forkhead box-O 1 (FOXO1), Carbonic anhydrase 9 (CA9), C-X-C motif chemokine ligand 9 (CXCL9), and GTPase, IMAP family member 7 (GIMAP7) in the tissue microarray of PAAD.

Lymph node ratio predicts prognosis in patients with surgically resected invasive pancreatic cystic neoplasms.

BACKGROUND: In current days, the prevalence of pancreatic cystic neoplasms (PCN) is on the rise. Lymph node ratio (LNR) has emerged as a promising prognostic factor in pancreatic adenocarcinoma (PDAC). However, the prognostic value of LNR in patients with invasive PCN remains unknown. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) database to retrieve the baseline characteristics and clinical tumor variables of patients diagnosed with PCN between 1988 and 2014. Survival analyses were performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with patient prognosis. RESULTS: A total of 10,656 PCN cases were initially identified. Based on our exclusion criteria, our analyses included data from 1246 cases, of which 479 were patients with lymph node involvement. Patients with high LNR had shorter overall survival (OS) than patients with low LNR (median OS, 13 vs. 21 months; P=0). Our univariate and multivariate analyses identified LNR (P=0) and grade (P=0.010) as independent prognostic factors in patients with invasive PCN. CONCLUSIONS: Our findings suggest that LNR is a reliable, independent prognostic factor in patients with invasive PCN, strongly associated with OS and cancer-specific survival (CSS). LNR may represent a promising prognostic factor alternative to the AJCC (the American Joint Committee on Cancer) N stage in patients with node-positive PCN.

The aberrant expression of ADAR1 promotes resistance to BET inhibitors in pancreatic cancer by stabilizing c-Myc.

Pancreatic cancer is a malignant tumor with the worst prognosis worldwide. This cancer type requires new insight to help with diagnosis and, eventually, treatment. Adenosine deaminases acting on RNA 1 (ADAR1) is reportedly overexpressed in many types of tumors, such as lung, liver, breast, and esophageal cancers. However, the biological significance and specific mechanism of ADAR1 in pancreatic cancer have not been explored. In this study, we reveal that the expression level of ADAR1 is significantly up-regulated in pancreatic cancer tissues. We also find that highly expressed ADAR1 is closely associated with poor prognosis in pancreatic cancer specimens. Overexpressed ADAR1 equally increased the growth activity of pancreatic cancer cells in vivo and in vitro. We further demonstrate that ADAR1 stabilizes c-Myc through AKT signaling, which contributes to cancer cell resistance to BET inhibitors in pancreatic cancer cells. Moreover, we reveal that EZH2 regulates ADAR1 expression, and EZH2 and BET inhibitors show synergistic inhibition in pancreatic cancer. Collectively, these findings suggest that ADAR1 could serve as a new diagnostic and prognostic marker for the treatment of pancreatic cancer.

FGD1 promotes tumor progression and regulates tumor immune response in osteosarcoma via inhibiting PTEN activity.

Rationale: Mesenchymal cell-derived osteosarcoma is a rare malignant bone tumor affecting children and adolescents. PTEN down-regulation or function-loss mutation is associated with the aggressive of osteosarcoma. Explicating the regulatory mechanism of PTEN might highlight new targets for improving the survival rate of osteosarcoma patients. Methods: The clinical relevance of FGD1 was examined by the TCGA data set, Western blotting and immunohistochemistry of osteosarcoma microarray slides. Functional assays, such as the MTS assay, colony formation assay and xenografts, were used to determine the biological role of FGD1 in osteosarcoma. The protein-protein interaction between FGD1 and PTEN was detected via co-immunoprecipitation. The relationship between FGD1 and PD-L1 was examined by Western blot analysis, RT-qPCR and immunohistochemistry. Results: In this study, analysis of the TCGA data set of sarcomas revealed that FGD1 was over-expressed with the highest P values. Then, we demonstrated that FGD1 was also abnormally up-regulated in osteosarcoma with unfavorable prognosis. Aberrant expressed FGD1 promoted the osteosarcoma tumor cell proliferation and invasion. Moreover, we found that FGD1 was participated in activating PI3K/AKT signaling pathway by interacting with PTEN. Finally, we showed that FGD1 was capable of regulating the tumor immune response via the PTEN/PD-L1 axis in osteosarcoma. Conclusions: Our data suggested that abnormally over-expressed FGD1 functions as an oncogenic protein to promote osteosarcoma progression through inhibiting PTEN activity and activating PI3K/AKT signaling. Notably, FGD1 increased PD-L1 expression in a PTEN dependent manner and modulated the sensitivity of immune checkpoint-based immunotherapy in osteosarcoma. Thus, FGD1 might be a potential target for improving the survival rate of osteosarcomas.

FBP1 binds to the bromodomain of BRD4 to inhibit pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumour that is characteristically unresponsive to most chemotherapeutic regimens. Bromodomain and extra terminal domain (BET) inhibitors that specifically repress the function of BET family proteins, such as BRD4, are under evaluation in clinical trials for their activity in repressing cancer growth. However, resistance to BET inhibitors has hindered their further clinical application in pancreatic cancer. We previously reported that FBP1 contributes to the resistance to BET inhibitors, but the underlying mechanism of this resistance remains unclear. Herein, we demonstrate that FBP1 is a binding partner of BRD4 in pancreatic cancer cells. We reveal that FBP1 binds to the BD2 domain of BD4 in an acetylation-dependent manner. Moreover, we found that Tip60 and HDAC3 were key to the acetylation and de-acetylation of FBP1 at K110 and K113, which are critical for mediating FBP1-BRD4 binding in pancreatic cancer cells. Furthermore, our data indicate that FBP1 decreases the expression of genes downstream of BRD4 to inhibit pancreatic cancer cell progression. Our results, therefore, provide evidence of the novel anti-tumour effect of FBP1 via its blockade of BRD4 function in pancreatic cancer cells.

The m6A-Related mRNA Signature Predicts the Prognosis of Pancreatic Cancer Patients.

N6-methyladenosine (m6A) has an important epitranscriptomic modification that controls cancer self-renewal and cell fate. The addition of m6A to mRNA is a reversible modification. The deposition of m6A is encoded by a methyltransferase complex involving three homologous factors, jargonized as "writers," "erasers," and "readers." However, their roles in pancreatic adenocarcinoma (PAAD) are underexploited. With the use of The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we provided an mRNA signature that may improve the prognostic prediction of PAAD patients based on the genetic status of m6A regulators. PAAD patients with genetic alteration of m6A regulators had worse disease-free and overall survival. After comparing PAAD groups with/without genetic alteration of m6A regulators, we identified 196 differentially expressed genes (DEGs). Then, we generated a 16-mRNA signature score system through least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Multivariate cox regression analysis demonstrated that a high-risk score significantly correlates with poor prognosis. Moreover, time-dependent receiver operating characteristic (ROC) curves revealed it was effective in predicting the overall survival in both training and validation sets. PAH, ZPLD1, PPFIA3, and TNNT1 from our signature also exhibited an independent prognostic value. Collectively, these findings can improve the understanding of m6A modifications in PAAD and potentially guide therapies in PAAD patients.

Pulmonary papillary squamous cell carcinoma: a population-based analysis of incidence, treatment, and prognosis.

BACKGROUND: Pulmonary papillary squamous cell carcinoma (PSCC) is a rare variant of pulmonary squamous cell carcinoma (SCC). This study aims to improve relevant understanding and demonstrate the incidence, treatment, and prognosis of pulmonary PSCC using a population-based database. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to extract data of cases diagnosed with PSCC from 1973 to 2015 and analyze the incidence, treatment, and prognosis. RESULTS: A total of 151 pulmonary PSCC cases were identified. The incidence of pulmonary PSCC cases in 2015 was 0.009 per 100,000 persons. The tumor grade of pulmonary PSCC cases was significantly lower than that of SCC cases (P<0.001). Both cancer-specific (CSS) and overall survival (OS) of pulmonary PSCC were significantly higher than those of other pulmonary SCCs (P<0.001). The outcomes of pulmonary PSCC cases receiving surgery were significantly better than cases without surgery (P<0.001). On the contrary, patients with radiotherapy had a worsened prognosis compared with those without radiotherapy (P<0.05). As expected, the prognosis of pulmonary PSCC cases receiving surgery was significantly better than that of pulmonary PSCC cases receiving chemotherapy and radiotherapy (both P<0.05). CONCLUSIONS: Our population-based evidence shows that pulmonary PSCC, as a rare cancer, has a better prognosis compared with other pulmonary SCCs. Surgery was the only effective treatment to improve CSS and OS, while chemotherapy was ineffective and radiotherapy worsened prognosis.

Improving Speech Related Facial Action Unit Recognition by Audiovisual Information Fusion.

It is challenging to recognize facial action unit (AU) from spontaneous facial displays, especially when they are accompanied by speech. The major reason is that the information is extracted from a single source, i.e., the visual channel, in the current practice. However, facial activity is highly correlated with voice in natural human communications. Instead of solely improving visual observations, this paper presents a novel audiovisual fusion framework, which makes the best use of visual and acoustic cues in recognizing speech-related facial AUs. In particular, a dynamic Bayesian network is employed to explicitly model the semantic and dynamic physiological relationships between AUs and phonemes as well as measurement uncertainty. Experiments on a pilot audiovisual AU-coded database have demonstrated that the proposed framework significantly outperforms the state-of-the-art visual-based methods in terms of recognizing speech-related AUs, especially for those AUs whose visual observations are impaired during speech, and more importantly is also superior to audio-based methods and feature-level fusion methods, which employ low-level audio features, by explicitly modeling and exploiting physiological relationships between AUs and phonemes.