Sex Differences in All-Cause Inpatient Mortality Risk in Gastric Cancer: Nationwide Inpatient Population-Based Study.

Objective The purpose of this study is to evaluate the differences in demographic characteristics, comorbidities, and hospital outcomes in gastric cancer inpatients by sex and evaluate the risk factors for in-hospital mortality in gastric cancer inpatients by sex. Methods We conducted a cross-sectional study using the nationwide inpatient sample (NIS, 2019). Our sample included 22,415 adult inpatients (age ≥18 years) hospitalized with a primary discharge diagnosis of gastric cancer that was identified by the international classification of diseases, 10th revision (ICD-10) codes of C16.x. Independent univariate binomial logistic regression models were used to evaluate the odds ratio (OR) of predictors associated with all-cause in-hospital mortality in gastric cancer inpatients by sex. Results The total number of patients admitted with gastric cancer was 22,415, out of which 62.7% were males and 37.3% were females, with the mean age at the admission of 65.5 years and 66.4 years, respectively. While studying comorbidities, we found that 41.5% percent of all patients had gastric cancer with metastasis, and there existed a significantly higher prevalence in males (42.2% vs. 40.4% in females). Other important and statistically significant comorbid conditions that were prevalent in these patients include complicated diabetes (12.2%), obesity (12.1%), depression (8%), and alcohol abuse (3.1%). Females between 50-59 years of age were at 2.5 times increased risk of mortality compared to those less than 40 years of age (OR: 2.5; 95% CI: 1.28-4.95). Conclusion Females of the age group 50-59 years are at greater risk of all-cause inpatient mortality due to gastric cancer. Black males are at increased risk of all-cause inpatient mortality compared to White males. Gastric cancer incidence and mortality rates have been down trending with the development of screening and better treatment options, but it still continues to be a major burden on the healthcare system.

Author Correction: Force-exerting perpendicular lateral protrusions in fibroblastic cell contraction.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Force-exerting perpendicular lateral protrusions in fibroblastic cell contraction.

Aligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and achieve elongated shapes. Activated fibroblasts are able to contract, perpetuating the alignment of these fibers. This poorly understood feedback process is critical in chronic fibrosis conditions, including cancer. Here, using fiber networks that serve as force sensors, we identify "3D perpendicular lateral protrusions" (3D-PLPs) that evolve from lateral cell extensions named twines. Twines originate from stratification of cyclic-actin waves traversing the cell and swing freely in 3D to engage neighboring fibers. Once engaged, a lamellum forms and extends multiple secondary twines, which fill in to form a sheet-like PLP, in a force-entailing process that transitions focal adhesions to activated (i.e., pathological) 3D-adhesions. The specific morphology of PLPs enables cells to increase contractility and force on parallel fibers. Controlling geometry of extracellular networks confirms that anisotropic fibrous environments support 3D-PLP formation and function, suggesting an explanation for cancer-associated desmoplastic expansion.

Inositol polyphosphate multikinase is a metformin target that regulates cell migration.

Metformin has been shown to alter cell adhesion protein expression, which is thought to play a role in its observed antitumor properties. We found that metformin treatment down-regulated integrin ß1 concomitant with the loss of inositol polyphosphate multikinase (IPMK) in murine myocytes, adipocytes, and hepatocytes. To determine if IPMK was upstream of integrin ß1 expression, we examined IPMK-/- mouse embryonic fibroblast cells and found that integrins ß1 and ß3 gene expression was reduced by half, relative to wild-type cells, whereas focal adhesion kinase (FAK) activity and Rho/Rac/Cdc42 protein levels were increased, resulting in migration defects. Using nanonet force microscopy, we determined that cell:extracellular matrix adhesion and cell contractility forces were decreased, confirming the functional relevance of integrin and Rho protein dysregulation. Pharmacological studies showed that inhibition of both FAK1 and proline-rich tyrosine kinase 2 partially restored integrin ß1 expression, suggesting negative regulation of integrin ß1 by FAK. Together our data indicate that IPMK participates in the regulation of cell migration and provides a potential link between metformin and wound healing impairment.-Tu-Sekine, B., Padhi, A., Jin, S., Kalyan, S., Singh, K., Apperson, M., Kapania, R., Hur, S. C., Nain, A., Kim, S. F. Inositol polyphosphate multikinase is a metformin target that regulates cell migration.