On Improving an Integrated Inventory Model for a Single Vendor and Multiple Buyers with Ordering Cost Reduction

In this paper, we propose a new model for improving lot size as obtained on applying the model given in “An integrated inventory model for a single vendor and multiple buyers with ordering cost reduction” (Int. J. Production Economics 73 203-215) proposed by Woo, Hsu, and Wu (2001) and our model provides a lower or equal joint total relevant cost as compared to Woo, Hsu, and Wu’s model. And a numerical study based on the example used by Woo, Hsu, and Wu is presented

Effectiveness of early rhythm control in improving clinical outcomes in patients with atrial fibrillation:a systematic review and meta-analysis

BackgroundCurrent guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients.MethodsWe systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model.ResultsA total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86-0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71-0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69-0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70-0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88-0.92), and ACS (HR = 0.86, 95% CI: 0.76-0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results.ConclusionsOur current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year.RegistrationThe study protocol was registered to PROSPERO (CRD42021295405)

Amino Acid Deprivation Promotes Tumor Angiogenesis through the GCN2/ATF4 Pathway

AbstractAs tumors continue to grow and exceed their blood supply, nutrients become limited leading to deficiencies in amino acids (AAD), glucose (GD), and oxygen (hypoxia). These alterations result in significant changes in gene expression. While tumors have been shown to overcome the stress associated with GD or hypoxia by stimulating vascular endothelial growth factor (VEGF)-mediated angiogenesis, the role of AAD in tumor angiogenesis remains to be elucidated. We found that in human tumors, the expression of the general control non-derepressible 2 (GCN2, an AAD sensor) kinase is elevated at both protein and mRNA levels. In vitro studies revealed that VEGF expression is universally induced by AAD treatment in all five cell lines tested (five of five). This is in contrast to two other angiogenesis mediators interleukin-6 (two of five) and fibroblast growth factor 2 (two of five) that have a more restricted expression. Suppressing GCN2 expression significantly decreased AAD-induced VEGF expression. Silencing activating transcription factor 4 (ATF4), a downstream transcription factor of the GCN2 signaling pathway, is also associated with strong inhibition of AAD-induced VEGF expression. PKR-like kinase, the key player in GD-induced unfolded protein response is not involved in this process. In vivo xenograft tumor studies in nonobese diabetic/severe combined immunodeficient mice confirmed that knockdown of GCN2 in tumor cells retards tumor growth and decreases tumor blood vessel density. Our results reveal that the GCN2/ATF4 pathway promotes tumor growth and angiogenesis through AAD-mediated VEGF expression and, thus, is a potential target in cancer therapy

Isospin dependence of projectile-like fragment production at intermediate energies

The cross sections of fragments produced in 140 $A$ MeV $^{40,48}$Ca + $^9$Be and $^{58,64}$Ni + $^9$Be reactions are calculated by the statistical abration-ablation(SAA) model and compared to the experimental results measured at the National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University. The fragment isotopic and isotonic cross section distributions of $^{40}$Ca and $^{48}$Ca, $^{58}$Ni and $^{64}$Ni, $^{40}$Ca and $^{58}$Ni, and $^{48}$Ca and $^{64}$Ni are compared and the isospin dependence of the projectile fragmentation is studied. It is found that the isospin dependence decreases and disappears in the central collisions. The shapes of the fragment isotopic and isotonic cross section distributions are found to be very similar for symmetric projectile nuclei. The shapes of the fragment isotopic and isotonic distributions of different asymmetric projectiles produced in peripheral reactions are found very similar. The similarity of the distributions are related to the similar proton and neutron density distributions inside the nucleus in framework of the SAA model.Comment: 7 pages, 4 figures; to be published in Phys Rev

The role of N-terminal pro-B-type natriuretic peptide in prognostic evaluation of heart failure

Heart failure (HF) is a growing challenge in the Asia Pacific region. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established tool for diagnosis of HF; however, it is relatively underutilized in predicting adverse outcomes in HF. Multiple studies have demonstrated the prognostic role of NT-proBNP in HF. A single value of NT-proBNP >5000 pg/mL predicts a worse outcome in hospitalized patients with HF with reduced ejection fraction (HFrEF). In stable outpatients with HFrEF, NT-proBNP > 1000 pg/mL predicts a poorer prognosis. NT-proBNP provides the same prognostic information in patients with HF with preserved ejection fraction (HFpEF) as in those with HFrEF. An expert panel composed of cardiologists mainly from Asia Pacific region was convened to discuss the utility of NT-proBNP in HF prognostication. This article summarizes available scientific evidence and consensus recommendations from the meeting

Role of miR-182 in response to oxidative stress in the cell fate of human fallopian tube epithelial cells

High grade serous ovarian carcinoma (HGSC) is a DNA instable tumor and its precursor is commonly found originating from the fimbriated end of the fallopian tube secretory epithelial (FTSE) cells. The local stresses via ovulation and related inflammation are risks for HGSC. In this study, we examined the cellular and molecular responses of FTSE cells to stress. We found that excess intracellular reactive oxygen species (ROS) in normal FTSE cells upregulated a subset of microRNA expression (defined as ROSmiRs). Most ROSmiRs' expression and function were influenced and regulated by p53, and together they drove the cells into stress-induced premature senescence (SIPS). However, ROS-induced miR-182 is regulated by β-catenin, not by p53. In normal FTSE cells, miR-182 overexpression triggers cellular senescence by p53-mediated upregulation of p21. Conversely, in cells with p53 mutations, miR-182 overexpression no longer enhances p21 but functions as an “Onco-miR”. p53 dysfunction is a prerequisite for miR-182-mediated tumorigenesis. In addition, we found that human follicular fluid could significantly induce intracellular ROS in normal FTSE cells. These findings suggest that ROS and p53 mutations may trigger a series of events, beginning with overexpressing miR-182 by ROS and β-catenin, impairing the DNA damage response, promoting DNA instability, bypassing senescence and eventually leading to DNA instable tumors in FTSE cells

Prognostic Significance of Serum Cysteine-Rich Protein 61 in Patients with Acute Heart Failure

Background/Aims: Cyr61-cysteine-rich protein 61 (CCN1/CYR61) is a multifunctional matricellular protein involved in the regulation of fibrogenesis. Animal experiments have demonstrated that CCN1 can inhibit cardiac fibrosis in cardiac hypertrophy. However, no study has been conducted to assess the relation between serum CCN1 and prognosis of acute heart failure (AHF). Methods: We measured the serum CCN1 levels of 183 patients with AHF, and the patients were followed up for 6 months. The associations between CCN1 levels and some clinical covariates, especially left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), atrial fibrillation and age, were estimated. The AHF patients were followed up for 6 months. The endpoint was all-cause mortality. Kaplan-Meier curve analysis and multivariable Cox proportional hazards analysis were employed to evaluate the prognostic ability of CCN1. We used calibration, discrimination and reclassification to assess the mortality risk prediction of adding CCN1. Results: Serum CCN1 concentrations in AHF patients were significantly increased compared with those in individuals without AHF (237 pg/ml vs. 124.8 pg/ml, p< 0.001). CCN1 level was associated with the level of NT-proBNP (r=0.349, p< 0.001) and was not affected by LVEF, eGFR, age or atrial fibrillation in AHF patients. Importantly, Kaplan-Meier curve analysis illustrated that the AHF patients with serum CCN1 level > 260 pg/ ml had a lower survival rate (p< 0.001). Multivariate Cox hazard analysis suggests that CCN1 functions as an independent predictor of mortality for AHF patients (LgCCN1, hazard ratio 5.825, 95% confidence interval: 1.828-18.566, p=0.003). In addition, the inclusion of CCN1 in the model with NT-proBNP significantly improved the C-statistic for predicting death (0.758, p< 0.001). The integrated discrimination index was 0.019 (p< 0.001), and the net reclassification index increased significantly after addition of CCN1 (23.9%, p=0.0179). Conclusions: CCN1 is strongly predictive of 6-month mortality in patients with AHF, suggesting serum CCN1 as a promising candidate prognostic biomarker for AHF patients