Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer.

Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples.

Contemporary management of major haemorrhage in critical care.

Haemorrhagic shock is frequent in critical care settings and responsible for a high mortality rate due to multiple organ dysfunction and coagulopathy. The management of critically ill patients with bleeding and shock is complex, and treatment of these patients must be rapid and definitive. The administration of large volumes of blood components leads to major physiological alterations which must be mitigated during and after bleeding.

Blood transfusions post kidney transplantation are associated with inferior allograft and patient survival-it is time for rigorous patient blood management.

Background: Patient Blood Management (PBM), endorsed by the World Health Organisation is an evidence-based, multi-disciplinary approach to minimise inappropriate blood product transfusions. Kidney transplantation presents a particular challenge to PBM, as comprehensive evidence of the risk of transfusion is lacking. The aim of this study is to investigate the prevalence of post-transplant blood transfusions across multiple centres, to analyse risk factors for transfusion and to compare transplant outcomes by transfusion status.

Investigation of Risk Factors for Hospitalization of COVID-19 Patients with Diabetes in Najaf, Iraq.

Preliminary findings indicate that patients with diabetes mellitus (DM) are at additional risk of infecting with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is associated with increased mortality in these patients. Hyperglycemia can affect inflammatory and immune responses, which leads patients to severe COVID-19 consequences. The present study investigated risk factors for hospitalized COVID-19 patients with DM in Najaf, Iraq.

Phosphatidylinositol 3-kinase signaling pathway and inflammatory bowel disease: Current status and future prospects.

Inflammatory bowel disease (IBD) is a chronic life-limiting disease of gastrointestinal tract characterized by widespread enteric inflammation. IBD is a multifactorial disease, and different environmental, microbial, and immune-related factors give rise to the development of disease. Among several factors, the preponderance of pro-inflammatory T helper 17 cells over the anti-inflammatory regulatory T cells augments inflammation in the intestinal mucosa.

THE RELEVANCE OF RS6777038 AND RS6444082 OF IGF2BP2 GENE POLYMORPHISM AND TYPE 2 DIABETES MELLITUS: A CASE CONTROL STUDY.

Objective: The aim: We investigate IGF2BP2 gene polymorphisms (rs6777038 and rs6444082) association with T2DM of Iraqi sample.

Patients And Methods: Materials and methods: The study involves 800 participants that divided to a healthy control group (400) and T2DM patients (400). Fasting blood sugar (FBS), triglycerides (Tgs), high-density lipoprotein cholesterol (HDL-Ch), total cholesterol (T-Ch), low-density lipoprotein cholesterol (LDL-Ch), and fasting insulin measured for both participant groups.

The Potential of Artificial Intelligence to Detect Lymphovascular Invasion in Testicular Cancer.

Testicular cancer is the most common cancer in men aged from 15 to 34 years. Lymphovascular invasion refers to the presence of tumours within endothelial-lined lymphatic or vascular channels, and has been shown to have prognostic significance in testicular germ cell tumours. In non-seminomatous tumours, lymphovascular invasion is the most powerful prognostic factor for stage 1 disease.

Nanoparticle-based "Two-pronged" approach to regress atherosclerosis by simultaneous modulation of cholesterol influx and efflux.

Reduction of lipoprotein uptake by macrophages and stimulation of cholesterol efflux are two essential steps required for atherosclerotic plaque regression. We used the optimized mannose-functionalized dendrimeric nanoparticle (mDNP)-based platform for macrophage-specific delivery of therapeutics to simultaneously deliver SR-A siRNA (to reduce LDL uptake) and LXR ligand (LXR-L, to stimulate cholesterol efflux) - a novel "Two-pronged" approach to facilitate plaque regression. mDNP-mediated delivery of SR-A siRNA led to a significant reduction in SR-A expression with a corresponding decrease in uptake of oxLDL.

Long-term safety and efficacy of N8-GP in previously treated adults and adolescents with hemophilia A: Final results from pathfinder2.

Background: N8-GP (turoctocog alfa pegol; Esperoct , Novo Nordisk A/S, Bagsvaerd, Denmark) is a glycoPEGylated human recombinant factor VIII with a half-life of ~1.6-fold of standard FVIII products. pathfinder2 (NCT01480180) was a multi-national, open-label trial of N8-GP in previously treated adolescent and adult patients with severe hemophilia A.

Extracorporeal Life Support Enhances the Forward Pressure Wave to Cause a Mismatch between Cardiac Oxygen Demand and Supply.

Extracorporeal life support (ECLS) is a world-famous life-saving method. Until now, changes in arterial wave properties due to ECLS have remained unexamined. In this study, we determined the effects of ECLS on arterial wave properties and ventricular/arterial coupling in male Wistar rats with the measured aortic pressure alone.

The Relationship Between Air Pollution and Lung Cancer in Nonsmokers in Taiwan.

Introduction: For never-smokers (smoked <100 lifetime cigarettes), lung cancer (LC) has emerged as an important issue. We aimed to investigate the effects of prevalence changes in tobacco smoking and particulate matter (PM) 2.5 (PM) levels on LC in Taiwan, in relation to contrasting PM levels, between Northern Taiwan (NT) and Southern Taiwan (ST).

The impact of low alcohol consumption on the liver and inflammatory cytokines in diabetic rats.

Background: Diabetes mellitus (DM) and alcohol consumption is still one of the important research models that simulate variable clinical conditions and metabolic diseases, such as alcoholic liver diseases.

Objectives: The aim of this study was to evaluate the long-term cumulative effects of low alcohol consumption on the liver tissue, biochemical assays and some inflammatory cytokines in experimentally-induced DM rats.

Material And Methods: Ethanol was administered in the drinking water (3% v/v) for 30 days to adult male Sprague-Dawley rats, with or without DM induced by streptozocin injection.

Intestine-specific expression of human chimeric intestinal alkaline phosphatase attenuates Western diet-induced barrier dysfunction and glucose intolerance.

Intestinal epithelial cell derived alkaline phosphatase (IAP) dephosphorylates/detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen. We have earlier demonstrated that consumption of high-fat high-cholesterol containing western type-diet (WD) significantly reduces IAP activity, increases intestinal permeability leading to increased plasma levels of LPS and glucose intolerance. Furthermore, oral supplementation with curcumin that increased IAP activity improved intestinal barrier function as well as glucose tolerance.

FAM198B Is Associated with Prolonged Survival and Inhibits Metastasis in Lung Adenocarcinoma via Blockage of ERK-Mediated MMP-1 Expression.

The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for lung cancer. FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals.

HOXA5 and p53 cooperate to suppress lung cancer cell invasion and serve as good prognostic factors in non-small cell lung cancer.

Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region.

SPANXA suppresses EMT by inhibiting c-JUN/SNAI2 signaling in lung adenocarcinoma.

SPANXA (Sperm Protein Associated with the Nucleus on the X-chromosome, family members A1/A2) acts as a cancer-testis antigen expressed in normal testes, but dysregulated in various tumors. We found that SPANXA is highly expressed in low-invasive CL1-0 cells compared with isogenous high-invasive CL1-5 cells. SPANXA was preferably expressed in tumor tissues and associated with the prolonged survival of lung adenocarcinomas.

Implementation of POCT in the diabetic clinic in a large hospital.

Aim: Point-of-care testing (POCT) is gaining renewed interest, especially in resource-limiting primary health care, due to rise in prevalence of communicable and non-communicable diseases hence POCT needscontinuous appraisal.

Methods: Random glucose and glycated haemoglobin (HbA1c) were measured in 104 diabetic patients using standard laboratory multichannel analyzer 917. The utility of venous blood compared to capillary blood in measuring HbA1c was evaluated in a subset of 20 patients using a POCT device, DCA Vantage.

Small Molecule T315 Promotes Casitas B-Lineage Lymphoma-Dependent Degradation of Epidermal Growth Factor Receptor via Y1045 Autophosphorylation.

Rationale: Despite the fact that tyrosine kinase inhibitors (TKIs) have been found effective in treating patients harboring activating mutations of epidermal growth factor receptor (EGFR), an acquired secondary mutation, T790M, which lowers the affinity to TKIs, can lead to EGFR TKI resistance after this standard treatment.

Objectives: To evaluate the effect of small molecule T315 on EGFR degradation and its therapeutic efficacy in vitro and in vivo.

Methods: Lung adenocarcinoma cells were treated with T315, and cell proliferation and apoptotic proportion were determined by the CellTiter 96 AQueous MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay and flow cytometry.

Autophagy limits proliferation and glycolytic metabolism in acute myeloid leukemia.

Decreased autophagy contributes to malignancies, however it is unclear how autophagy impacts on tumour growth. Acute myeloid leukemia (AML) is an ideal model to address this as (i) patient samples are easily accessible, (ii) the hematopoietic stem and progenitor population (HSPC) where transformation occurs is well characterized, and (iii) loss of the key autophagy gene in hematopoietic stem and progenitor cells (HSPCs) leads to a lethal pre-leukemic phenotype in mice. Here we demonstrate that loss of results in an identical HSPC phenotype as loss of , confirming a general role for autophagy in HSPC regulation.

Rhodomycin A, a novel Src-targeted compound, can suppress lung cancer cell progression via modulating Src-related pathways.

Src activation is involved in cancer progression and the interplay with EGFR. Inhibition of Src activity also represses the signalling pathways regulated by EGFR. Therefore, Src has been considered a target molecule for drug development.

HOXA5 inhibits metastasis via regulating cytoskeletal remodelling and associates with prolonged survival in non-small-cell lung carcinoma.

Homeobox genes comprise a family of regulatory genes that contain a common homeobox domain and act as transcription factors. Recent studies indicate that homeobox A5 (HOXA5) may serve as a tumour suppressor gene in breast cancers. However, the precise role and the underlying mechanism of HOXA5 in lung cancer remain unclear.

Understanding of genetic inheritance among Xhosa-speaking caretakers of children with hemophilia.

Hemophilia A and B are X-linked recessive inherited bleeding disorders that have a profound impact on the family of affected individuals. Education is vital to enable women to appreciate the implications of being a carrier and the implications for a prospective child. Prior research has shown that cultural, socio-economic and linguistic issues in South Africa are major barriers to communication for first-language Xhosa-speakers.