An hp hp -version spectral collocation method for fractional Volterra integro-differential equations with weakly singular kernels

We present a multi-step spectral collocation method to solve Caputo-type fractional integro-differential equations (FIDEs) involving weakly singular kernels. We reformulate the problem as the second type Volterra integral equation (VIE) with two different weakly singular kernels. Based on these integral equations, we construct a multi-step Legendre-Gauss spectral collocation scheme for the problem. The $hp$-version convergence is established rigorously. To demonstrate the effectiveness of the suggested method and the validity of the theoretical results, the results of some numerical experiments are presented

The role played by ailanthone in inhibiting bone metastasis of breast cancer by regulating tumor-bone microenvironment through the RANKL-dependent pathway

Introduction: Bone metastasis of breast cancer (BC) is a process in which the disruption of the bone homeostatic microenvironment leads to an increase in osteoclast differentiation. Ailanthus altissima shows an inhibitory effect on osteoclast differentiation. Ailanthone (AIL) refers to a natural compound isolated from Ailanthus altissima, a Chinese herbal medicine, and has effective anti-tumor activity in numerous cell lines. Its impact on bone metastases for BC is yet unclear.Methods: We measured the effect of AIL on MDA-MB-231 cells by wound healing experiments, Transwell and colony formation experiment. Using the Tartrate-resistant Acid Phosphatase (TRAP) staining tests, filamentous (F-actin) staining and bone resorption test to detect the effect of AIL on the osteoclast cell differentiation of the Bone Marrow-derived Macrophages (BMMs), activated by the MDA-MB-231 cell Conditioned Medium (MDA-MB-231 CM) and the Receptor Activator of Nuclear factor-κB Ligand (RANKL),and to explore its possibility Mechanisms. In vivo experiments verified the effect of AIL on bone destruction in breast cancer bone metastasis model mice.Results:In vitro, AIL significantly decrease the proliferation, migration and infiltration abilities of MDA-MB-231 cells at a safe concentration, and also reduced the expression of genes and proteins involved in osteoclast formation in MDA-MB-231 cells. Osteoclast cell differentiation of the BMMs, activated by MDA-MB-231 CM and RANKL, were suppressed by AIL in the concentration-dependent manner. Additionally, it inhibits osteoclast-specific gene and protein expression. It was noted that AIL inhibited the expression of the osteoclast differentiation-related cytokines RANKL and interleukin-1β (IL-1β) that were secreted by the MDA-MB-231 cells after upregulating the Forkhead box protein 3 (FOXP3) expression. Furthermore, AIL also inhibits the expression of the Mitogen-Activated Protein Kinase (MAPK), Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), and Nuclear factor-κB Ligand (NF-κB) signaling pathways, which then suppresses the MDA-MB-231CM-induced development of Osteoclasts.Conclusion: Our study shows that AIL blocks osteoclast differentiation in the bone metastasis microenvironment by inhibiting cytokines secreted by BC cells, which may be a potential agent for the treatment of BC and its secondary bone metastasis

Case report: Peroral endoscopic myotomy for acute pandysautonomia-associated distal esophageal spasm in a child

Acute pandysautonomia-associated distal esophageal spasm is a rare disease with an unclear etiology. Here, we describe a 12-year-old boy with an acute pandysautonomia-associated distal esophageal spasm who was treated using a peroral endoscopic myotomy (POEM). The patient's clinical features included recurrent dysphagia, nausea, vomiting, growth retardation, and signs of autonomic nerve dysfunction (e.g., a decreased production of tears and sweat, and an increased production of saliva). Signs of the distal esophageal spasm were visible in upper gastrointestinal radiography, endoscopy, and high-resolution esophageal manometry. After the POEM, the patient exhibited improvements in nausea and vomiting, and his dysphagia symptoms were relieved by the 6-month follow-up visit. However, the patient's neurological problems persisted. The satisfactory short-term clinical responses in our patient suggest that POEM is feasible, safe, and effective for the treatment of acute pandysautonomia-associated distal esophageal spasms in children

LncRNA LCPAT1 Mediates Smoking/ Particulate Matter 2.5-Induced Cell Autophagy and Epithelial-Mesenchymal Transition in Lung Cancer Cells via RCC2

Background/Aims: Ecological studies have shown that air pollution and prevalence of cigarette smoking are positively correlated. Evidence also suggests a synergistic effect of cigarette smoking and PM2.5 exposure (Environmental Particulate Matter ≤ 2.5 µm in diameter) on lung cancer risk. We aimed to evaluate the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality and determine its underlying mechanisms in vitro. Methods: “MOVER” method was used to analyze the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality. Cell autophagy and malignant behaviors induced by cigarette smoke extract (CSE) and PM2.5 exposure were examined in vitro. Gene expression was examined by qRT-PCR and western blot. RNA and protein interaction was determined using a RNA binding protein immunoprecipitation assay. Results: An increased risk for lung cancer death (RERI (the relative excess risk) =0.28) was observed with a synergistic interaction between cigarette smoking and PM2.5 pollution. Cell migration, invasion, EMT (epithelial-mesenchymal transition) and autophagy were elevated when lung cancer cells were treated with CSE and PM2.5 in combination. A lncRNA, named lung cancer progression-association transcript 1 (LCPAT1), was up-regulated after the treatment of CSE and PM2.5, and knocking down the lncRNA impaired the effect of CSE and PM2.5 on lung cancer cells. In addition, LCPAT1 was shown to bind to RCC2, and RCC2 mediated the effect of LCPAT1 on cell autophagy, migration, invasion and EMT in lung cancer. Conclusions: Our results suggest that combined exposure to CSE and PM2.5 induces LCPAT1 expression, which up-regulates autophagy, and promotes lung cancer progression via RCC2

Pengaruh sense of school belonging terhadap student's misbehavior

Penelitian ini bertujuan untuk mengetahu pengaruh sense of school belonging terhadap student’s misbehavior. Penelitian ini merupakan penelitian korelasional dengan menggunakan teknnik pengumpulan data berupa skala likert yaitu skala sense of school belonging dan skala student’s misbehavior masing masing terdiri dari 30 aitem yang sudah melalui uji coba. Skala sense of school belonging memiliki reabilitas sebesar 0,899 sedangkan skala student’s misbehavior memiliki reabilitas sebesar 0,924. Subjek penelitian berjumlah 144 siswa dari jumlah populasi sebesar 576 siswa. Pengambilan data menggunakan simple random sampling. Hasil penelitian menujukkan bahwa terdapat pengaruh sense of school belonging terhadap student’s misbehavior dengan nilai signifikansi 0,000 < 0,05. Dalam table model summary pada analisis regresi linier sederhana, sense of school belonging memberikan pengaruh sebesar 17,7% terhadap student’s misbehavior. Pada table correlation, terdapat nilai koerfisien korelasi sebesar -0,420 yang berarti semakin tinggi sense of school belonging maka semakin rendah student’s misbehavior yang dilakukan oleh siswa

Prognostic and predictive value of clinical and biochemical factors in breast cancer patients with bone metastases receiving "metronomic" zoledronic acid

<p>Abstract</p> <p>Background</p> <p>To assess prognostic and predictive effects of clinical and biochemical factors in our published randomized study of a weekly low dose (metronomic arm) versus a conventional dosage of zoledronic acid (conventional arm) in breast cancer patients with bone metastases.</p> <p>Methods</p> <p>Treatment outcome of 60 patients with bone metastases were used to assess impacts of following potential prognostic factors, estrogen receptor status, lymph node status, 2 year-disease free interval (DFI), numbers of chemotherapy regimens administered, interventions, and serum levels of VEGF, N-telopeptide of type I collagen (NTx), CEA, and CA 15-3.</p> <p>Results</p> <p>In univariate analyses, patients pretreated with 2 or fewer chemotherapy regimens, ER-positive tumors, 3 or fewer lymph nodes, DFI of more than 2 years, serum VEGF of less than 500 pg/mL after 3 months of intervention, serum CEA and CA 15-3 of less than ULN, and baseline serum NTx of less than 18 nM BCE had significantly longer progression free survival (PFS). The multivariate analysis showed that ER positivity (hazard ratio [HR], 0.295; 95% confidence interval [CI], 0.141-0.618; P = 0.001), serum VEGF of less than 500 pg/mL after 3 months of intervention (HR, 2.220; 95% CI, 1.136-4.338; P = 0.020), baseline serum NTx of less than 18 nM BCE (HR, 2.842; 95% CI, 1.458-5.539; P = 0.001), and 2 or fewer chemotherapy regimens received (HR, 7.803; 95% CI, 2.884-21.112; P = 0.000) were associated with a better PFS. When evaluating the predictive effect of the biochemical factors, an interaction between NTx and zoledronic acid intervention was shown (P = 0.005). The HR of weekly low dose versus a conventional dosage of zoledronic acid was estimated to be 2.309 (99% CI, 1.067-5.012) in patients with baseline serum NTx of more than 18 nM BCE, indicating a superiority of weekly low dose of zoledronic acid.</p> <p>Conclusions</p> <p>ER, serum VEGF level after intervention, and numbers of chemotherapy regimens administered are prognostic but not predictive factors in breast cancer patients with bone metastases. Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid.</p> <p>Trial registration</p> <p>ClinicalTrials.gov unique identifier: ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00524849">NCT00524849</a></p