SOX2 Determines Lineage Restriction: Modeling Lung Squamous Cell Carcinoma in the Mouse.

In this issue of Cancer Cell, Ferone et al. demonstrate that SOX2 not only drives lung tumor formation but also restricts tumor lineage to squamous cell carcinoma (LSCC), regardless of cell of origin. This novel LSCC model should facilitate identification of key oncogenic drivers and treatment strategies for this lung cancer subtype.

Effect of Anti-TNF Agents on Postoperative Outcomes in Inflammatory Bowel Disease Patients: a Single Institution Experience.

Background: Anti-tumor necrosis factor (TNF) agents have been an integral part in the treatment of inflammatory bowel disease. However, a subset of inflammatory bowel disease patients ultimately requires surgery and up to 30 % of them have undergone treatment with anti-TNF agents. Studies assessing the effect of anti-TNF agents on postoperative outcomes have been inconsistent.

PKCι regulates nuclear YAP1 localization and ovarian cancer tumorigenesis.

Atypical protein kinase Cι (PKCι) is an oncogene in lung and ovarian cancer. The PKCι gene PRKCI is targeted for frequent tumor-specific copy number gain (CNG) in both lung squamous cell carcinoma (LSCC) and ovarian serous carcinoma (OSC). We recently demonstrated that in LSCC cells PRKCI CNG functions to drive transformed growth and tumorigenicity by activating PKCι-dependent cell autonomous Hedgehog (Hh) signaling.

Targeting oncogenic protein kinase Cι for treatment of mutant KRAS LADC.

Lung cancer is the leading cause of cancer death in the US with ∼124,000 new cases annually, and a 5 y survival rate of ∼16%. Mutant KRAS-driven lung adenocarcinoma (KRAS LADC) is a particularly prevalent and deadly form of lung cancer. Protein kinase Cι (PKCι) is an oncogenic effector of KRAS that activates multiple signaling pathways that stimulate transformed growth and invasion, and maintain a KRAS LADC tumor-initiating cell (TIC) phenotype.

Surgical Management of the Primary Tumor in Stage IV Colorectal Cancer: A Confirmatory Retrospective Cohort Study.

Background: Observational studies have suggested that patients with stage IV colorectal cancer who undergo surgical resection of the primary tumor (SRPT) have better survival. Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control prognostic variables such as performance status are major critiques to the findings of the observational studies.

Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model.

Stabilin-1 is a multifunctional scavenger receptor expressed on alternatively-activated macrophages. Stabilin-1 mediates phagocytosis of "unwanted-self" components, intracellular sorting, and endocytic clearance of extracellular ligands including SPARC that modulates breast cancer growth. The expression of stabilin-1 was found on tumor-associated macrophages (TAM) in mouse and human cancers including melanoma, lymphoma, glioblastoma, and pancreatic insulinoma.

Implementation of Nationwide Real-time Whole-genome Sequencing to Enhance Listeriosis Outbreak Detection and Investigation.

Listeria monocytogenes (Lm) causes severe foodborne illness (listeriosis). Previous molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE), were critical in detecting outbreaks that led to food safety improvements and declining incidence, but PFGE provides limited genetic resolution. A multiagency collaboration began performing real-time, whole-genome sequencing (WGS) on all US Lm isolates from patients, food, and the environment in September 2013, posting sequencing data into a public repository.

Perioperative adverse events in distal femur fractures treated with intramedullary nail versus plate and screw fixation.

Background: To compare 30-day outcomes in patients treated for a distal femur (DF) fracture with plate fixation (PF) or intramedullary nail (IMN).

Methods: Differences in rates of any adverse events (AAE), serious adverse events (SAE), infectious complications, and mortality were explored between groups in the ACS-NSQIP database.

Results: There were 511 PF and 44 IMN patients.

Language Matters: Race, Trust, and Outcomes in the Pediatric Emergency Department.

Objective: Trust in physicians and health care system has been positively associated with health care outcomes. The purpose of this study is to explore the relationships among race, ethnicity, language, trust, and health care outcomes.

Methods: This prospective cross-sectional study took place in the pediatric emergency department of an intercity hospital.

Regional Lymph Nodes Status and Ratio of Metastatic to Examined Lymph Nodes Correlate with Survival in Stage IV Colorectal Cancer.

Background: Although lymph nodes status and the ratio of metastatic to examined lymph node (LNR) are important prognostic factors in early-stage colorectal cancer (CRC), their significance in patients with metastatic disease remains unknown. The study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC.

Methods: A cohort of 1109 eligible patients who were diagnosed with synchronous metastatic CRC in Saskatchewan during 1992-2010 and underwent primary tumor resection was evaluated.

Protein Kinase Cι Drives a NOTCH3-dependent Stem-like Phenotype in Mutant KRAS Lung Adenocarcinoma.

We report that the protein kinase Cι (PKCι) oncogene controls expression of NOTCH3, a key driver of stemness, in KRAS-mediated lung adenocarcinoma (LADC). PKCι activates NOTCH3 expression by phosphorylating the ELF3 transcription factor and driving ELF3 occupancy on the NOTCH3 promoter. PKCι-ELF3-NOTCH3 signaling controls the tumor-initiating cell phenotype by regulating asymmetric cell division, a process necessary for tumor initiation and maintenance.

Comparison of Clinical Risk Factors Among Pediatric Patients With Single Admission, Multiple Admissions (Without Any 7-Day Readmissions), and 7-Day Readmission.

Background And Objective: Readmissions have received increasing attention. The goal of this study was to identify demographic and clinical factors associated with hospital utilization and 7-day readmissions.

Methods: This retrospective case-control study of inpatient and observation encounters was conducted at a freestanding children's hospital.

Discharge Destination After Total Joint Arthroplasty: An Analysis of Postdischarge Outcomes, Placement Risk Factors, and Recent Trends.

Background: This study aimed to compare risk of postdischarge adverse events in elective total joint arthroplasty (TJA) patients by discharge destination, identify risk factors for inpatient discharge placement and postdischarge adverse events, and stratify TJA patients based on these risk factors to identify the most appropriate discharge destination.

Methods: Patients who underwent elective primary total hip or knee arthroplasty from 2011 to 2013 were identified in the National Surgical Quality Improvement Program database. Bivariate and multivariate analyses were assessed using perioperative variables.

Innovation in Healthcare Delivery: Commentary on an Evolutionary Approach.

Zwarenstein (2015) proposes a novel approach to healthcare innovation that parallels biological evolution, based on stimulation and reward of multiple small competing innovation projects conducted in the field by decentralized teams. Projects would be designed with explicit outcome targets and results would be widely disseminated and publicly available. More successful projects would be grown and spread.

Chromosome-scale shotgun assembly using an in vitro method for long-range linkage.

Long-range and highly accurate de novo assembly from short-read data is one of the most pressing challenges in genomics. Recently, it has been shown that read pairs generated by proximity ligation of DNA in chromatin of living tissue can address this problem, dramatically increasing the scaffold contiguity of assemblies. Here, we describe a simpler approach ("Chicago") based on in vitro reconstituted chromatin.

The chromosome 3q26 OncCassette: A multigenic driver of human cancer.

Recurrent copy number variations (CNVs) are genetic alterations commonly observed in human tumors. One of the most frequent CNVs in human tumors involves copy number gains (CNGs) at chromosome 3q26, which is estimated to occur in >20% of human tumors. The high prevalence and frequent occurrence of 3q26 CNG suggest that it drives the biology of tumors harboring this genetic alteration.

Surgical outcomes in patients with chronic obstructive pulmonary disease undergoing abdominal operations: An analysis of 331,425 patients.

Background: Chronic obstructive pulmonary disease (COPD) affects >15 million individuals in the United States and is a common comorbidity in patients undergoing surgery; therefore, the association between COPD in patients and postoperative surgical outcomes was investigated. The objective of this study was to assess the associations between COPD and postoperative morbidity, mortality, and hospital duration of stay.

Methods: Patients who underwent cholecystectomy, appendectomy, small bowel resection, partial colectomy, hepatic resection, gastrectomy, pancreatectomy, and ventral hernia repair with and without COPD (n = 331,425) in the National Surgical Quality Improvement Program database from 2007 to 2010 were studied.

Comparison of Short-Term Outcomes of Geriatric Distal Femur and Femoral Neck Fractures: Results From the NSQIP Database.

Purpose: To compare and contrast postoperative complications in the geriatric population following open reduction and internal fixation (ORIF) for (DF) fractures relative to femoral neck (FN) fractures.

Methods: Patients aged 65 years and older in the American College of Surgeons National Surgical Quality Improvement Program database who underwent ORIF for FN fractures or DF fractures from 2005 to 2012 were identified. Differences in rates of any adverse events (AAEs), serious adverse events (SAEs), infectious complications, and mortality between groups were explored using univariate and multivariate analyses.

Resolving Uncertainty About the Intolerance of Uncertainty Scale-12: Application of Modern Psychometric Strategies.

In this study, we evaluated the factor structure, reliability estimates, item parameters, and differential correlates of the short form of the Intolerance of Uncertainty Scale (Carleton, Norton, & Asmundson, 2007 ) in samples of undergraduate women (n = 387) and men (n = 276) ranging in age from 18 to 49 years (M = 20.20, SD = 3.91).

Safety of Tourniquet Use in Total Knee Arthroplasty in Patients With Radiographic Evidence of Vascular Calcifications.

Tourniquets are often used in total knee arthroplasty (TKA) to improve visualization of structures, shorten operative time, reduce intraoperative bleeding, and improve cementing technique. Despite these advantages, controversy remains regarding the safety of tourniquet use. Tourniquets have been associated with nerve palsies, vascular injury, and muscle damage.

Heart rate variability as a potential indicator of positive valence system disturbance: A proof of concept investigation.

One promising avenue toward a better understanding of the pathophysiology of positive emotional disturbances is to examine high-frequency heart rate variability (HRV-HF), which has been implicated as a potential physiological index of disturbances in positive emotional functioning. To date, only a few psychopathology relevant studies have systematically quantified HRV-HF profiles using more ecologically valid methods in everyday life. Using an experience-sampling approach, the present study examined both mean levels and intra-individual variability of HRV-HF - as well as comparison measures of cardiovascular arousal, sympathetic activity, and gross somatic movement - in everyday life, using ambulatory psychophysiological measurement across a six-day consecutive period among a spectrum of community adult participants with varying degrees of positive valence system disturbance, including adults with bipolar I disorder (BD; n=21), major depressive disorder (MDD; n=17), and healthy non-psychiatric controls (CTL; n=28).

Laparoscopic-Assisted Transversus Abdominis Plane Block for Postoperative Pain Control in Laparoscopic Ventral Hernia Repair: A Randomized Controlled Trial.

Background: Laparoscopic ventral hernia repair (LVHR) is associated with considerable postoperative pain. Transversus abdominis plane (TAP) blocks have proven effective in controlling postoperative pain in a variety of laparoscopic abdominal operations. To date, no studies have focused on TAP blocks in LVHR.