A real-world analysis of second-line treatment option, Gemcitabine plus Anlotinib and anti-PD1, in advanced pancreatic cancer.

BACKGROUND: In the second-line treatment of advanced pancreatic cancer (APC), there is only one approved regimen based on the phase III NAPOLI-1 trial. However, for patients progressing after Nab-paclitaxel and Gemcitabine (Nab-P/Gem) or Nab-P combinations, second-line treatment were very limited. METHODS: This is a retrospective single-center analysis of patients. Our aim was to determine the effectiveness and tolerability of a novel regimen, gemcitabine plus Anlotinib and anti-PD1, in APC patients and to compare it with oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX) in the second-line setting who have failed on the first-line Nab-P combinations. RESULTS: In total, twenty-three patients received Gemcitabine plus Anlotinib and anti-PD1 in the second-line, 28 patients were treated with FOLFORINOX. There was no significant difference in overall survival (OS) or progression free survival (PFS) for either of the two sequences (p > 0.05). Patients who received Gemcitabine plus Anlotinib and anti-PD1 had a median PFS of 4.0 months (95% CI: 1.1-6.9) versus 3.5 months (95% CI 1.8-5.2) in FOLFORINOX group (p = 0.953). The median OS of Gemcitabine plus Anlotinib and anti-PD1 was 9.0 months (95% CI: 4.0-13.7) and 8.0 months (95% CI: 5.5-10.5) in FOLFORINOX group (p = 0.373). Grade ≥3 treatment-emergent adverse events (AEs) occurred for 13% of patients with Gemcitabine plus Anlotinib and anti-PD1 and 40% for FOLFORINOX. CONCLUSION: Our data confirms the effectiveness of Gemcitabine plus Anlotinib and anti-PD1 as a well-tolerated regimen in the second-line treatment of APC and extends available data on its use as a second-line treatment option when compared with FOLFIRINOX.

Survival outcome of different treatment sequences in patients with locally advanced and metastatic pancreatic cancer.

BACKGROUND: Despite some therapeutic advances, improvement in survival rates of unresectable and/or metastatic pancreatic ductal adenocarcinoma (PDAC) has been minimal over recent decade. We aimed to evaluate the impact of different treatment sequences on clinical outcomes of advanced PDAC at our academic institution. METHODS: In this single institution retrospective analysis, we assessed characteristics and survival rates of unresectable and/or metastatic pancreatic PDAC patients who started a systemic treatment between 01/2015 and 12/2021. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model. RESULTS: The number of 285 patients received at least two lines of treatment, but only 137 patients were suitable for third-line treatment. Subgroup analysis showed that thirty-seven patients received A line (gemcitabine/nab-paclitaxel or nab-paclitaxel combined therapy to FOLFIRINOX) therapy, 37 patients received B line (nab-paclitaxel combined therapy to gemcitabine combined therapy to FOLFIRINOX) therapy, 21 patients received C line (nab-paclitaxel combined therapy to gemcitabine combined therapy to oxaliplatin or irinotecan combined therapy) therapy. Survival rates for different treatment lines were significantly different and median overall survival (OS) was 14.00, 18.00, and 14.00 months, respectively (p<0.05). CONCLUSION: Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the treatment sequences on survival outcome when considering the entire management in advanced PDAC.

The effects of errorless psychomotor training in the Y balance lower limb reaching task.

This study investigated the training effect of errorless psychomotor training, a motor training method with perceptual, attentional, and psychological manipulation, in a balance-related, lower limb reaching task (Y balance reaching task) on dynamic balance by young adults. Thirty-nine participants (Mean age = 27.03 years, SD = 2.64 years) were trained with different psychomotor training methods in the Y balance reaching task. Results illustrate that errorless psychomotor training significantly improved the participants' dynamic balance and proprioceptive abilities. Additionally, gaze fixation duration on target during reaching decreased after errorless psychomotor training, suggesting that errorless psychomotor training could decrease visual information demand and be concurrently compensated by up-weighting on proprioception. This multisensory reweighting and cross-modal attention could contribute to the improvement of dynamic balance ability in sports.

Association between Dietary Vitamin E Intake and Human Papillomavirus Infection among US Adults: A Cross-Sectional Study from National Health and Nutrition Examination Survey.

Persistent high-risk human papillomavirus (HPV) infection is responsible for most genital, anal, and oropharyngeal cancers, in which men contribute significantly to infection and subsequent tumorigenesis in women. Vitamin E has been shown to be associated with vaginal HPV infection and cervical cancer. However, the association of vitamin E consumption with HPV infection among the overall population remains unclear. We investigate the association between vitamin E consumption and genital and oral HPV infection in both men and women. We used cross-sectional data from the National Health and Nutrition Examination Survey between 2013 and 2016 to collect details on their dietary vitamin E intake, genital and oral HPV infection status, and other essential variables. In total, 5809 participants aged 18-59 years were identified, with overall prevalence of high-risk and low-risk HPV infection of 23.7% and 21.1%, respectively. Compared with the lowest vitamin E group Q1 (<5.18 mg/day), the adjusted OR for vitamin E consumption and overall high-risk HPV infection in Q2 (5.18-7.54 mg/day), Q3 (7.55-10.82 mg/day), and Q4 (>10.82 mg/day) were 0.91 (95% CI: 0.81-1.03, p = 0.134), 0.77 (95% CI: 0.69-0.87, p < 0.001), and 0.72 (95% CI: 0.65-0.80, p < 0.001), respectively. Restricted cubic spline regression showed a linear relationship between vitamin E consumption and overall high-risk HPV infection. This linear relationship also existed for vitamin E consumption and overall low-risk HPV infection. After being stratified by gender and site, vitamin E consumption was inversely related to vaginal low- and high-risk HPV infection, penile high-risk HPV infection, and male oral low-risk HPV infection. In conclusion, we identified inverse linear relationships between dietary vitamin E intake and overall high- and low-risk HPV infection. Future well-designed longitudinal studies are still required to validate the impact of vitamin E on HPV carcinogenesis.

Functional identification and prediction of lncRNAs in esophageal cancer.

Esophageal cancer is a highly lethal malignancy with poor prognosis, and the identification of molecular biomarkers is crucial for improving diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the development and progression of esophageal cancer. However, due to the time cost of biological experiments, only a small number of lncRNAs related to esophageal cancer have been discovered. Currently, computational methods have emerged as powerful tools for identifying and characterizing lncRNAs, as well as predicting their potential functions. Therefore, this article proposes a transformer-based method for identifying esophageal cancer-related lncRNAs. Experimental results show that the AUC and AUPR of this method are superior to other comparison methods, with an AUC of 0.87 and an AUPR of 0.83, and the identified lncRNA targets are closely associated with esophageal cancer. We focus on the role of esophageal cancer-related lncRNAs in the immune microenvironment, and fully explore the functions of the target genes regulated by lncRNAs. Enrichment analysis shows that the predicted target genes are related to multiple pathways involved in the occurrence, development, and prognosis of esophageal cancer. This not only demonstrates the effectiveness of the method but also indicates the accuracy of the prediction results.

Immune function of colon cancer associated miRNA and target genes.

Introduction: Colon cancer is a complex disease that involves intricate interactions between cancer cells and theimmune microenvironment. MicroRNAs (miRNAs) have recently emerged as critical regulators of gene expression in cancer, including colon cancer. There is increasing evidence suggesting that miRNA dysregulation plays a crucial role in modulating the immune microenvironment of intestinal cancer. In particular, miRNAs regulate immune cell activation, differentiation, and function, as well as cytokine and chemokine production in intestinal cancer. It is urgent to fully investigate the potential role of intestinal cancer-related miRNAs in shaping the immune microenvironment. Methods: Therefore, this paper aims to identify miRNAs that are potentially associated with colon cancer and regulate a large number of genes related to immune function. We explored the role of these genes in colon cancer patient prognosis, immune infiltration, and tumor purity based on data of 174 colon cancer patients though convolutional neural network, survival analysis and multiple analysis tools. Results: Our findings suggest that miRNA regulated genes play important roles in CD4 memory resting cells, macrophages.M2, and Mast cell activated cells, and they are concentrated in the cytokinecytokine receptor interaction pathway. Discussion: Our study enhances our understanding of the underlying mechanisms of intestinal cancer and provides new insights into the development of effective therapies. Additionally, identification of miRNA biomarkers could aid in diagnosis and prognosis, as well as guide personalized treatment strategies for patients with intestinal cancer.

Alloying nickel and cobalt with iron on ZSM-5 for tuning competitive hydrogenation reactions for selective one-pot conversion of furfural to gamma-valerolactone.

One-pot conversion of furfural, a biomass-derived platform chemical, to gamma-valerolactone (GVL), a fuel additive and green solvent, involves multiple steps of hydrogenation. Among these reactions, the deep hydrogenation of the furan ring in furfural interrupts GVL formation over Ni or Co-based catalysts. In this study, a method of alloying Ni and Co with Fe over a ZSM-5 support was proposed for tackling excessive activity of the catalyst for hydrogenation. The results indicated that the formation of binary NiFe and CoFe alloys in Ni-Co-Fe/ZSM-5 enhanced the dispersion of metallic species, reduction of metal oxides, formation of more Lewis acidic sites, and the adsorption of the C-O functionality of the furan ring, while lowering the capability for adsorption/activation of H2 and the adsorption of the CC group of the furan ring. These factors together reduced the activity for the hydrogenation of the furan ring in furfural, but enhanced the hydrogenation of the CO in ethyl levulinate (EL). The kinetic study confirmed that the hydrogenation of EL was the rate-determining step. The coordination of the dual alloys, NiFe and CoFe, in the bifunctional Ni-Co-Fe/ZSM-5 catalyst rendered superior activity for selective one-pot conversion of furfural to GVL with a yield of 85.7%.

A composite indicator of derived neutrophil-lymphocyte ratio and lactate dehydrogenase correlates with outcomes in pancreatic carcinoma patients treated with PD-1 inhibitors.

Background: There are currently no established biomarkers that can predict whether advanced pancreatic carcinoma (PC) patients would benefit from immune checkpoint inhibitors (ICIs). Our study investigated whether the pretreatment composite biomarker of derived neutrophil-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) can be used as a reliable prognostic factor for the survival of PC patients receiving PD-1 inhibitor therapy. Methods: Patients with advanced PC treated with PD-1 inhibitors at a single center from September 2015 to September 2020 were included. The high levels of dNLR (≥3) and LDH (≥250 U/L) were considered to be risk factors. Based on these two risk factors, patients in this study were categorized into two risk groups: the good dNLR-LDH group, without risk factors, and the intermediate/poor dNLR-LDH group, with one to two risk factors. Overall survival (OS) and progression-free survival (PFS) served as this study's primary and secondary endpoints. Cox regression models were used to identify independent prognostic factors for survival benefit. Results: There were 98 patients in our study. The good group included 61 (62.2%) patients and the intermediate/poor group included 37 (37.8%). The overall patients with PC who received immunotherapy had a median OS of 12.1 months, and the good dNLR-LDH group had a significantly longer OS compared with the intermediate/poor dNLR-LDH group (44.2 vs. 6.4 months; p < 0.010); median PFS was 3.7 and 2.5 months (p = 0.010). The number of metastatic sites >2 and immunotherapy as third-line or later was associated with worse PFS, and the line of immunotherapy and the dNLR-LDH indicator were independent prognostic factors for OS, according to multivariate analysis. Conclusion: The pretreatment composite biomarker of dNLR and LDH can be used as a prognostic biomarker in patients with advanced PC treated with PD-1 inhibitors.

FAM117A Is a New Prognostic Marker of Lung Adenocarcinoma and Predicts Sensitivity to PD0332991.

Lung cancer is the second most common cancer and the leading cause for cancer mortality worldwide. Accelerated cell cycle progression is a well-characterized hallmark for cancer. The present study aims to identify biomarkers for clinical outcomes of lung cancer patients and their sensitivity to CDK inhibitors. To this end, bioinformatics analysis of transcriptome datasets from the Cancer Genome Atlas (TCGA) was first performed to identify survival-related genes; cell proliferation assay, colony formation assay, flow cell cytometry, western blot, EDU labelling, and xenograft models were then used to confirm the potential roles of the identified factors. Our results identified the decreased FAM117A expression as the most significant survival related factor for poor outcome. The cell cycle transition from G1 to S phase was suppressed upon FAM117A overexpression and was promoted upon FAM117A knockdown. Accordingly, the tumor cell growth induced by FAM117A depletion was completely blocked by treatment with PD0332991, which has been approved for cancer therapy. In summary, our work identified FAM117A as a new prognostic marker for poor outcomes of lung cancer patients, predicting sensitivity to PD0332991 treatment.

Pyrolysis of cellulose: Correlation of hydrophilicity with evolution of functionality of biochar.

Biochar is a carbonaceous material from pyrolysis of biomass, the application of which is governed by its various properties such as the distribution of the functionalities and the associated hydrophilic/hydrophobic nature. This study particularly focused on the correlation of functionalities of biochar with its polarities by conducting the pyrolysis of cellulose from 200 to 700 °C and the characterization of the biochar. The results demonstrated that -OH, instead of CO or C-O-C, played decisive roles in formation of the biochar with hydrophilic surface. The results showed that the maximum of -OH abundance and the aliphatic CH was reached at 440 °C. The significant transition of oxygen-rich functionalities to carbon-rich functionalities occurred in the temperature from 460 to 700 °C. The dominance of aromatization process above this temperature range resulted in the significant increase of hydrophobicity of the biochar. The hydrophilic surface was of importance for the use of biochar as support for promoting the dispersion of Cu in Cu/biochar by generating the bonding sites for chelating with Cu2+.

Response to olaparib in metastatic lung adenocarcinoma with germline BRCA2 mutation: a case report.

Mutation of BRCA2, a breast cancer susceptibility gene, is associated with the development of breast and ovarian cancer. Olaparib is an oral poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor, which has been proven to treat BRCA-mutated tumors effectively, especially breast and ovarian cancer. Here, we report a case of a germline BRCA2-mutated metastatic lung adenocarcinoma, non-small-cell lung cancer, responded well to olaparib. A 41-year-old man with no history of smoking was diagnosed with advanced lung adenocarcinoma. The patient was treated with bevacizumab, pemetrexed disodium, and cis-platinum in the first-line therapy of 6 months, followed by bevacizumab, Abraxane, and sintilimab treatments for another 6 months. As disease progression was confirmed and the presence of germline BRCA2 mutation, the combinational treatment of olaparib/anlotinib was applied to achieve partial response 1 month later, and the progression-free survival was extended for another 5 months. This study shows metastatic lung adenocarcinoma with BRCA2 mutation could also respond well to PARP inhibitor, broadening the spectrum of BRCA-mutated cancers suitable for olaparib therapy. With acquired resistance to chemotherapy, bevacizumab, and immunotherapy, the patient still gained significant benefits from the targeted therapy.

In situ characterization of functional groups of biochar in pyrolysis of cellulose.

Heating rate, an important parameter in pyrolysis, not only impacts distribution of pyrolysis products, but also affects evolution of functionality of biochar and further application of the biochar. In this study, an in situ Diffuse Reflection Infrared Fourier Transform Spectra (DRIFTS) technique was used to probe transformation of functional groups of the biochar derived from pyrolysis of cellulose at varied heating rate of 5, 10, 15 and 20 °C/min, aiming to draw an overall picture for the change of functional groups of the biochar versus the heating rate and pyrolysis temperature. The results showed the abundance of -OH, CH and CO experienced a maximum in 410 to 450 °C, depending on the specific heating rates, and then decreased with further increasing temperature via the conversion routes including dehydration, dehydrogenation and cracking. This led to carbonization of the biochar with monotonous increase of abundance of =C-H and CC functionality. Formation of the =C-H had a very close correlation with the removal of -C-H and -OH, especially the -C-H. Cracking of CO was one of the decisive factors for formation of CC. Nevertheless, cracking of C-O-C was much more difficult to be removed than that of CO and -OH, deterring the carbonization and leading to the retainment oxygen in the biochar.

Hyperprogressive Disease Caused by PD-1 Inhibitors for the Treatment of Pan-Cancer.

BACKGROUND: Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. RESULTS: In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0-4.2) vs. 7.3 months (95% CI, 5.9-8.7); P < 0.01). Factors related to HPD include more than 2 metastatic sites, ECOG performance status ≥ 2, hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors' analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. CONCLUSIONS: HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.

An IoT-Based Motion Tracking System for Next-Generation Foot-Related Sports Training and Talent Selection.

Motion tracking in different fields (medical, military, film, etc.) based on microelectromechanical systems (MEMS) sensing technology has been attracted by world's leading researchers and engineers in recent years; however, there is still a lack of research covering the sports field. In this study, we propose a new AIoT (AI + IoT) paradigm for next-generation foot-driven sports (soccer, football, takraw, etc.) training and talent selection. The system built is cost-effective and easy-to-use and requires much fewer computational resources than traditional video-based analysis on monitoring motions of players during training. The system built includes a customized wireless wearable sensing device (WWSDs), a mobile application, and a data processing interface-based cloud with an ankle attitude angle analysis model. Eleven right-foot male participators wore the WWSD on their ankle while each performed 20 instances of different actions in a formal soccer field. The experimental outcome demonstrates the proposed motion tracking system based on AIoT and MEMS sensing technologies capable of recognizing different motions and assessing the players' skills. The talent selection function can partition the elite and amateur players at an accuracy of 93%. This intelligent system can be an emerging technology based on wearable sensors and attain the experience-driven to data-driven transition in the field of sports training and talent selection and can be easily extended to analyze other foot-related sports motions (e.g., taekwondo, tumble, and gymnastics) and skill levels.

Divergent expression of DCLK1 in gastrointestinal neuroendocrine tumors and primary hepatic, gallbladder, and pancreatic neuroendocrine tumors.

Doublecortin-like kinase 1 (DCLK1) is reported to be a negative prognostic marker in colorectal cancer and is involved in tumorigenesis and progression through several miRNA pathways. In this study, We analyzed its expression in neuroendocrine tumor (NET) and explored its relation with survival outcome. 122 patients were enrolled in the study, including 60 cases of GI-NETs, 24 cases of primary hepatic NETs (PHNETs), 16 cases of gallbladder NETs (GBNETs) and 22 cases of pancreatic NETs (pNETs). IHC was performed for DCLK1 on tumor tissue. All patients underwent a baseline visit, histologic determination, and a follow-up for survival. In the 60 cases of GI-NETs, DCLK1 showed diffuse cytoplasmic expression. The positive rates of DCLK1, Syn and CgA were 100% (60/60), 100% (60/60) and 36.7% (22/60), respectively. However, DCLK1 showed negative staining in all of the 62 cases of PHNETs, GBNETs, and pNETs. The mean score of DCLK1, Syn, and CgA were (5.77±2.012), (5.13±2.078) and (2.68±2.797), respectively. DCLK1 was correlated with primary site (P<0.001) and Syn expression (P = 0.045). Additionally, in GI-NETs, we found that DCLK1 expression was associated with worse OS (log-rank = 5.212, P = 0.022). The divergent expression of DCLK1 in NETs suggests different functional roles of DCLK1 in different locations of NET within the digestive system. However, with the limited number of tumor samples, its outcome prediciton still needs further investigation. DCLK1 expression may aid in the diagnosis and prognosis of GI-NETs.

Expression and prognostic significance of doublecortin-like kinase 1 in patients with hepatocellular carcinoma.

Doublecortin-like kinase 1 (DCLK1), a putative cancer stem cell marker in intestinal and pancreatic tumors, is associated with tumor pathogenesis and progression, and poor survival outcomes in numerous types of cancer. However, DCLK1 expression and its prognostic value remain unclear in hepatocellular carcinoma (HCC). In the present study, the expression of DCLK1 was assessed using immunohistochemistry in 96 resected HCC and 68 adjacent tissue specimens. The staining intensity and the percentage of stained cells were scored on a scale of 0-3 and 0-4, respectively. Tissue was defined as positive for DCLK1 if the composite multiple score was >3. Cytoplasmic expression of DCLK1 was observed in HCC and adjacent tissue specimens with an expression rate of 81% (78/96) and 74% (50/68), respectively; the median score was 4.6 and 3.9, respectively, and no statistically significant difference was observed between HCC and adjacent tissues (P=0.087). DCLK1 expression was positively associated with intrahepatic metastasis (P=0.035). Furthermore, univariate analysis revealed that DCLK1 expression was significantly associated with poor disease-free survival (DFS) and overall survival (P=0.024 and 0.034). Multivariate analysis also demonstrated that DCLK1 expression was an independent prognostic factor for DFS in HCC (P=0.019; hazard ratio, 1.546; 95% confidence interval, 1.330-1.725). Stratified Kaplan-Meier survival curves revealed that DCLK1 expression predicted poorer DFS with respect to positivity for three characteristics: Portal venous metastasis, intrahepatic metastasis, and cirrhosis (P=0.020, P=0.007 and P=0.017, respectively). Collectively, the results of the present study suggested that DCLK1, functioning as a tumor promoter, is frequently overexpressed in HCC, and that DCLK1 expression is associated with poor DFS in patients with HCC. DCLK1 may represent a promising therapeutic target in HCC and requires further study.

1,2,4,5-Tetra-phenyl-1H-imidazole.

The asymmetric unit of the title compound, C(27)H(20)N(2), contains two independent mol-ecules, A and B. In both mol-ecules, the N atom in the 1-position and the C atom in the 5-position are statistically disordered [as 0.571 (8):0.429 (8) in A and 0.736 (9):0.264 (9) in B]. The phenyl rings in the 1-, 2-, 4- and 5-positions in A are twisted from the central imidazole ring by 84.3 (2), 21.6 (2), 21.5 (2) and 75.7 (2)°, respectively. The corresponding dihedral angles in B are 85.5 (2), 3.8 (2), 2.4 (2) and 81.7 (2)°, respectively.