The CXCR2-dependent role of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as a consequence of the accumulation of genetic mutations like Kras. Oncogenic Kras is known to propagate inflammatory signals such as CXCR2. PDAC is known for the prominent desmoplasia that enables therapy resistance and tumor dissemination, which is mainly mediated through cancer-associated fibroblasts (CAFs). Little is known about the connection between oncogenic Kras, CXCR2 signaling and CAFs. In this study, we show that CAFs can produce CXCR2 ligands and can respond to CXCR2 signaling. We indicated that through paracrine factors such as CXCL8 and FGF-2, CAFs support the survival of the aggressive PDAC cells and enable means for progression. We demonstrate that oncogenic Kras is associated with a subset of CAFs with a prominent secretory function mediated through CXCR2 signaling. Lastly, we exhibit a differential role of CXCR2 in PDAC that was dependent on genetic mutations, which may indicate a temporal context of CXCR2 roles in PDAC. Together, CAFs, as well as CXCR2, could still be worthy targets in PDAC in the III right context. Further studies that investigate the progression and timely roles of CAFs and CXCR2 are warranted

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Cancer-Associated Fibroblasts’ Functional Heterogeneity in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths in the USA. Desmoplasia and inflammation are two major hallmarks of PDAC. Desmoplasia, composed of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and infiltrating immune and endothelial cells, acts as a biophysical barrier to hinder chemotherapy and actively contributes to tumor progression and metastasis. CAFs represent a multifunctional subset of PDAC microenvironment and contribute to tumor initiation and progression through ECM deposition and remodeling, as well as the secretion of paracrine factors. Attempts to resolve desmoplasia by targeting CAFs can render an adverse outcome, which is likely due to CAFs heterogeneity. Recent reports describe subsets of CAFs that assume more secretory functions, in addition to the typical myofibroblast phenotype. Here, we review the literature and describe the relationship between CAFs and inflammation and the role of the secretory-CAFs in PDAC

Tumor-Associated Neutrophils in Cancer: Going Pro

The progression of cancer is not only about the tumor cell itself, but also about other involved players including cancer cell recruited immune cells, their released pro-inflammatory factors, and the extracellular matrix. These players constitute the tumor microenvironment and play vital roles in the cancer progression. Neutrophils—the most abundant white blood cells in the circulation system—constitute a significant part of the tumor microenvironment. Neutrophils play major roles linking inflammation and cancer and are actively involved in progression and metastasis. Additionally, recent data suggest that neutrophils could be considered one of the emerging targets for multiple cancer types. This review summarizes the most recent updates regarding neutrophil recruitments and functions in the tumor microenvironment as well as potential development of neutrophils-targeted putative therapeutic strategies

Hybrid Techniques of Facial Feature Image Analysis for Early Detection of Autism Spectrum Disorder Based on Combined CNN Features

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social communication and repetitive behaviors. The exact causes of ASD remain elusive and likely involve a combination of genetic, environmental, and neurobiological factors. Doctors often face challenges in accurately identifying ASD early due to its complex and diverse presentation. Early detection and intervention are crucial for improving outcomes for individuals with ASD. Early diagnosis allows for timely access to appropriate interventions, leading to better social and communication skills development. Artificial intelligence techniques, particularly facial feature extraction using machine learning algorithms, display promise in aiding the early detection of ASD. By analyzing facial expressions and subtle cues, AI models identify patterns associated with ASD features. This study developed various hybrid systems to diagnose facial feature images for an ASD dataset by combining convolutional neural network (CNN) features. The first approach utilized pre-trained VGG16, ResNet101, and MobileNet models. The second approach employed a hybrid technique that combined CNN models (VGG16, ResNet101, and MobileNet) with XGBoost and RF algorithms. The third strategy involved diagnosing ASD using XGBoost and an RF based on features of VGG-16-ResNet101, ResNet101-MobileNet, and VGG16-MobileNet models. Notably, the hybrid RF algorithm that utilized features from the VGG16-MobileNet models demonstrated superior performance, reached an AUC of 99.25%, an accuracy of 98.8%, a precision of 98.9%, a sensitivity of 99%, and a specificity of 99.1%

Impact of COVID-19 pandemic on transplant laboratories: How to mitigate?

A positive flow cytometry crossmatch (FCXM) due to donor specific antibodies (DSA) constitutes a risk for kidney transplantation; such a finding may indicates an unacceptable donor for this patient. However, positive FCXM in the absence of DSA is considered discordant and need further investigations. During COVID-19 pandemic, we observed 22% discordant results out of 445 FCXM performed during eight months period in our laboratory and another 7% were invalid due to high background negative control (NC). No study has addressed the impact of COVID-19 pandemic on FCXM and the overall pre-kidney transplant workups or described a solution to deal with these non-specific reactivities. Herein, we analyzed all FCXM results in SARS-CoV-2 seropositive patients and addressed how this pandemic affected significantly the pre-kidney transplant workups, highlighting both technical and financial implications. We also shared our modified FCXM procedures using dithiotheritol (DTT) sera treatment or blocking donor cells with negative control human serum (NCS) which we found to be successful to abrogate 98% of all discordant FCXM results and to validate all invalid results due to high background NC.In conclusion, COVID-19 pandemic has affected our HLA laboratory significantly by creating many false positive or invalid crossmatch results. Transplant laboratories must consider this before test interpretations and immune risk assessments. We recommend the use of DTT serum treatment to remove nonspecific bindings in the sera of kidney transplant candidates and the use of NCS-blocked donor cells to correct high background when performing FCXM in transplant candidates or donors with recent history of SARS-CoV-2 immunization respectively

Consumption habits of pregnant women in the Jazan region, Saudi Arabia: a descriptive study

Abstract Objective Maternal nutritional habits are critical for the health of both mother and offspring. Postpartum outcomes for mother and infant are strongly influenced by the mother’s nutritional status. Information about consumption habits among pregnant women in Saudi Arabia is scarce. Thus, this study aims to describe the consumption habits of pregnant women in the Jazan region, Saudi Arabia. Results Meat, fish, and fruits were consumed by 97%, 86%, and 90% of the sample. Sugary desserts, fast food, and canned food were consumed by 90%, 81%, and 71% of the sample. Caffeine, juices, and milk were consumed by 75%, 92%, and 81% of the sample. Previous percentages show general higher consumption habits of food and beverages. Over-the-counter medication was used by only 17%. Folic acid, iron, and calcium use by 77%, 64%, and 58% of the sample, respectively. These percentage shows conservative use of Over-the-counter medication and sub-optimal use of important dietary supplements. Moreover, there was a positive association between caffeine intake and trimesters. Furthermore, there was negative association between education level and fish intake. Finally, canned foods consumption was higher among low income pregnant women

Dilated cardiomyopathy associated with NRAP gene: a case series

Background: The genetic basis of dilated cardiomyopathy (DCM) is highly diverse, with over 100 known genes and several possibilities described. Nebulin-related-anchoring protein (NRAP) is an action-binding cytoskeletal protein that has a role in the myofibrillar assembly in the embryonic heart. It is primarily generated in striated and cardiac muscles. Case Presentation: We described three cases of DCM that were related to NRAP gene mutations [NM_001261463.1: c.3568G > T; p. (Glu1190*)]. Conclusion: Our data imply that biallelic nonsense mutations in the NRAP might be a genetic risk factor with limited penetrance and induce DCM at various ages. [JBCGenetics 2023; 6(1.000): 70-74