Pre-Menopausal Women With Breast Cancers Having High AR/ER Ratios in the Context of Higher Circulating Testosterone Tend to Have Poorer Outcomes

PurposeWomen with breast tumors with higher expression of AR are in general known to have better survival outcomes while a high AR/ER ratio is associated with poor outcomes in hormone receptor positive breast cancers mostly in post menopausal women. We have evaluated the AR/ER ratio in the context of circulating androgens specifically in patients younger than 50 years most of whom are pre-menopausal and hence have a high estrogenic hormonal milieu.MethodsTumor samples from patients 50 years or younger at first diagnosis were chosen from a larger cohort of 270 patients with median follow-up of 72 months. Expression levels of ER and AR proteins were detected by immunohistochemistry (IHC) and the transcript levels by quantitative PCR. Ciculating levels of total testosterone were estimated from serum samples. A ratio of AR/ER was derived using the transcript levels, and tumors were dichotomized into high and low ratio groups based on the third quartile value. Survival and the prognostic significance of the ratio was compared between the low and high ratio groups in all tumors and also within ER positive tumors. Results were further validated in external datasets (TCGA and METABRIC).ResultsEighty-eight (32%) patients were ≤50 years, with 22 having high AR/ER ratio calculated using the transcript levels. Circulating levels of total testosterone were higher in women whose tumors had a high AR/ER ratio (p = 0.02). Tumors with high AR/ER ratio had significantly poorer disease-free survival than those with low AR/ER ratio [HR-2.6 (95% CI-1.02–6.59) p = 0.04]. Evaluation of tumors with high AR/ER ratio within ER positive tumors alone reconfirmed the prognostic relevance of the high AR/ER ratio with a significant hazard ratio of 4.6 (95% CI-1.35–15.37, p = 0.01). Similar trends were observed in the TCGA and METABRIC dataset.ConclusionOur data in pre-menopausal women with breast cancer suggest that it is not merely the presence or absence of AR expression but the relative activity of ER, as well as the hormonal milieu of the patient that determine clinical outcomes, indicating that both context and interactions ultimately influence tumor behavior

Workload Control in Flow Shops with Bottleneck Shifting and Process Time Variability

Manufacturing industries struggle to devise precise planning and scheduling solutions due to unpredictable business situations. Additionally, uncertainties in production such as machine breakdowns, labour absenteeism, cycle time deviations, etc., would further deteriorate production plans and lead to uncertainty in decision-making processes. Flow shops with bottlenecks are particularly susceptible to these disturbances. Moreover, the random variations in cycle time variations can cause the bottleneck to shift between different stages. Literature indicates that conventional job release methods are ineffective in addressing these difficulties. In contrast, workload control methods would provide better solutions. Hence, a flow shop model has been developed and simulated using the variables like process time variations and bottleneck shifting on the discrete-event simulation software. The flow shop model incorporates realistic shop characteristics which are subjected to random process time variations, so as to assess the performance. The outcomes of the experimentation demonstrate that order release methods play a pivotal role in improving the performance of flow shops in more volatile situations

Influence of Farmer demographics and Supply Chain Issues on Organized Retailer Performance

Advances in information technology and increased social networking have increased health awareness among people in this era. The increased health awareness has prompted people to eat healthy and stay fit. In this regard, the food sector has seen tremendous demand in terms of good quality vegetables/fruits, cereals, with hygiene, nutrition, proteins etc. With the consumer willing to pay an extra premium for the quality expected, it has been observed that the producers are still offered low prices for a good quality produce whereas the intermediaries grab a huge share of the price paid by the consumer. This research tried to understand the supply chain with the farmers in focus and explored the influence of farmer demographics and the supply chain issues on the performance of the organized retail. Linear regression analysis was used to test the linear relationship of supply chain issues with organized retailer performance. The outcome of the study implies that independent variables like demographic characteristics and supply chain issues had no control over the retailer’s performance

Pancreatoblastoma masquerading as hepatoblastoma: A diagnostic dilemma

Clinicoradiological and histopathological differentiation of pancreatoblastoma from hepatoblastoma can often be a challenge in clinical practice owing to their peculiar resemblance. We report a case of a 4-year-old boy with a right hypochondriac region mass, which was diagnosed as hepatoblastoma on the basis of imaging, raised tumor marker, and biopsy; however, pancreatic origin of the mass was ascertained on exploration and pancreatoblastoma was confirmed on histopathology

Influence of Farmer demographics and Supply Chain Issues on Organized Retailer Performance

Advances in information technology and increased social networking have increased health awareness among people in this era. The increased health awareness has prompted people to eat healthy and stay fit. In this regard, the food sector has seen tremendous demand in terms of good quality vegetables/fruits, cereals, with hygiene, nutrition, proteins etc. With the consumer willing to pay an extra premium for the quality expected, it has been observed that the producers are still offered low prices for a good quality produce whereas the intermediaries grab a huge share of the price paid by the consumer. This research tried to understand the supply chain with the farmers in focus and explored the influence of farmer demographics and the supply chain issues on the performance of the organized retail. Linear regression analysis was used to test the linear relationship of supply chain issues with organized retailer performance. The outcome of the study implies that independent variables like demographic characteristics and supply chain issues had no control over the retailer’s performance

Bilateral nasolabial cysts - case report and review of literature

Nasolabial cyst is a non-odontogenic, extraosseous, soft tissue cyst, commonly unilateral, located in the nasolabial fold. Bilateral nasolabial cysts are of rare occurrence. This case report describes the multimodality imaging appearance of bilateral nasolabial cysts with a review of literature

A versatile method for enumeration and characterization of circulating tumor cells from patients with breast cancer

Aim: To establish a standardized protocol for the isolation and enumeration of circulating tumor cells (CTCs) from peripheral blood of patients with metastatic breast cancer.Methods: The protocol used tumor cells spiked in a lymphoid cell line with detection by flow cytometry and quantitative reverse transcription polymerase chain reaction (QRT-PCR). Cells of the human mammary cancer subtypes were spiked into Jurkat cells, which served as the lymphocyte designate in numbers from 10 to 500 per 105 Jurkat cells. This mixed population was probed for CD45, EpCAM, and pancytokeratin acquired from flow cytometry and characterized by microscopy. QRT-PCR was done for CK-19, MUC-1, EpCAM, and GAPDH. Validation was attained with blood samples from 22 patients with metastatic breast cancer and 20 healthy individuals.Results: Flow cytometry could detect 1 breast cancer cell per 100,000 Jurkat cells, with similar detection levels in the breast cancer subtypes. Samples from patients with breast cancer showed a range of CTCs from 1-85 per 10 mL of blood. Quantitation of expression for EpCAM, CK-19, Muc-1, and Her2neu confirmed the presence of CTCs in 76% of samples.Conclusion: Density gradient and immunomagnetic enrichment accomplished isolation of CTCs and quantitation was achieved using flow cytometry. Combined QRT-PCR and imaging further validated these findings, rendering a robust methodology

Effect of ranolazine on improvement of left ventricular dysfunction in patients with chronic stable angina: A randomized controlled clinical trial

Objectives: To study the effect of ranolazine on improvement of left ventricular (LV) dysfunction in comparison to trimetazidine in patients with chronic stable angina (CSA). Ranolazine is an anti-anginal agent that acts on the late inward sodium current and prevents pathologic intracellular calcium accumulation that leads to ischemia, myocardial dysfunction, and electrical instability. Methodology: After screening and obtaining informed consent, 29 patients with CSA who have sustained ST-Elevation Myocardial Infarction more than 12 weeks ago with LV ejection fraction (LVEF) ≤40% in a 2:1 ratio to receive ranolazine 500 mg BD (n = 19) or trimetazidine 35 mg BD (n = 10) were enrolled in the study. The patients were evaluated at the end of 8 weeks for the improvement in LV dysfunction by transthoracic echocardiography. Results: No significant difference was found in the baseline characteristics of the patients between the two groups except the increased body mass index among users of trimetazidine (26.3 ± 5.07 vs. 22.1 ± 3.26, P = 0.03). Study patients receiving ranolazine 500 mg BD for 8 weeks significantly improved the LVEF. No improvement was seen in diastolic function. Ranolazine was well tolerated among the patients. Conclusion: Ranolazine at a dose of 500 mg BD given for 8 weeks helps in improving the LVEF in patients with CSA and is a suitable option than trimetazidine among patients with CSA