Raahaugebarber9111
Changes in lipid metabolism pathways play a major role in colon carcinogenesis and development. Hence, we conducted a systematic analysis of lipid metabolism-related genes to explore new markers that predict the prognosis of colon adenocarcinoma (COAD).
The non-negative Matrix Factorization (NMF) algorithm was applied to identify the molecular subtypes based on lipid metabolism-related genes. A weighted correlation network analysis (WCGNA) was used to identify co-expressed genes, and Lasso multivariate Cox analysis was performed to build a risk prognosis model. A timer database was used to analyze the immune infiltration of the gene signature and the GSCALite database was used for genome-wide analysis of the gene signature.
TCGA-COAD samples were divided into 3 subtypes based on lipid metabolism-related genes. 2739 genes were identified by WGCNA analysis. Finally, an 8-gene signature (RTN2, FYN, HEYL, FAM69A, FBXL5, HMGN2, LGALS4, STOX1) was constructed that demonstrated good robustness in different datrapy. The HEYL, FYN, FAM69A, and RTN2 genes' expression was associated with the EMT pathway's activation, while LGALS4 and STOX1 were associated significantly with the EMT pathway's inhibition.
This study constructed an 8-gene signature as a novel marker to predict colon cancer patients' survival.
This study constructed an 8-gene signature as a novel marker to predict colon cancer patients' survival.Lung cancer has become a paradigm for precision medicine in oncology, and liquid biopsy (LB) together with radiomics may have a great potential in this scenario. They are both minimally invasive, easy to perform, and can be repeated during patient's follow-up. Also, increasing evidence suggest that LB and radiomics may provide an efficient way to screen and diagnose tumors at an early stage, including the monitoring of any change in the tumor molecular profile. This could allow treatment optimization, improvement of patients' quality of life, and healthcare-related costs reduction. Latest reports on lung cancer patients suggest a combination of these two strategies, along with cutting-edge data analysis, to decode valuable information regarding tumor type, aggressiveness, progression, and response to treatment. The approach seems more compatible with clinical practice than the current standard, and provides new diagnostic companions being able to suggest the best treatment strategy compared to conventional methods. To implement radiomics and liquid biopsy directly into clinical practice, an artificial intelligence (AI)-based system could help to link patients' clinical data together with tumor molecular profiles and imaging characteristics. AI could also solve problems and limitations related to LB and radiomics methodologies. Further work is needed, including new health policies and the access to large amounts of high-quality and well-organized data, allowing a complementary and synergistic combination of LB and imaging, to provide an attractive choice e in the personalized treatment of lung cancer.An automatic on-line dilution/on-line solid phase extraction (SPE) system has been developed for the detection of metabolites of the arachidonic acid cascade in platelets. The method allows the direct injection of larger quantities of centrifugates from cell suspensions previously treated with an equal volume of an acetonitrile/methanol mixture for protein precipitation. The method was used to study the effect of inhibitors of platelet arachidonic acid cascade enzymes (cytosolic phospholipase A2α, cyclooxygenase-1, thromboxane synthase, 12-lipoxygenase) and related targets (cyclooxygenase-2, microsomal prostaglandin E synthase-1, 5-lipoxygenase) in intact platelets after stimulation with calcium ionophore A23187. In addition to enzyme inhibition, the cell-damaging properties of the test compounds was determined by measuring the release of serotonin from the platelets into the incubation buffer.After decades of experience supporting surgical quality and safety by the American College of Surgeons, the American College of Surgeons Quality Verification Program was developed to help hospitals improve surgical quality, safety, and reliability. This review is the second of a 3-part review aiming to synthesize the evidence supporting the main principles of the American College of Surgeons Quality Verification Program. Evidence was systematically reviewed for 5 principles case review, peer review, credentialing and privileging, data for surveillance, and continuous quality improvement using data. MEDLINE was searched for articles published from inception to January 2019 and 2 reviewers independently screened studies for inclusion in a hierarchical fashion, extracted data, and summarized results in a narrative fashion. A total of 9,098 studies across the 5 principles were identified. After exclusion criteria, a total of 184 studies in systematic reviews and primary studies were included for assessment. The identified literature supports the importance of standardized processes and systems to identify problems and improve quality of care.
Acromegaly is associated with increased morbidity and mortality. Limited data are available on the utilization and costs of healthcare by these patients. This study assessed the impact of acromegaly on employees' health benefit (direct and indirect) costs and absenteeism.
A retrospective analysis was conducted of drug and medical claims and employer data (from January 2010 to April 2019) of patients with an acromegaly diagnosis and matched controls from a US employee database. Patient claims were tracked for 12 months post-diagnosis (or matched) date. Outcomes were analyzed using separate 2-part regression models, controlling for clinical, demographic, and job-related variables.
Forty-seven patients with acromegaly and 940 controls were identified. Cohorts were similar in most demographic and job-related variables. Patients with acromegaly had a significantly higher Charlson Comorbidity Index score, and higher incidence of claims for several comorbidities. Acromegaly drugs represented 16.3% of the acromegaly cohort's total costs. Total health benefit costs were $54,821 higher (P<0.05) for patients compared with controls, with direct costs representing 79.8% of the difference. Total indirect costs were higher for patients with acromegaly ($12,378 vs. $1,229 for controls), with short-term and long-term disability comprising most of the difference between the acromegaly and control groups. Patients with acromegaly had significantly more short-term disability days than controls (9.6 vs. 0.6 days, P=0.0117), but total sick days were similar for the two groups (1.6 vs. 1.1 days).
The presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.
The presence of acromegaly was associated with increased direct and indirect employee health benefit costs and increased work absenteeism.The unique fast spiking (FS) phenotype of cortical parvalbumin-positive (PV) neurons depends on the expression of multiple subtypes of voltage-gated potassium channels (Kv). PV neurons selectively express Kcns3, the gene encoding Kv9.3 subunits, suggesting that Kcns3 expression is critical for the FS phenotype. check details KCNS3 expression is lower in PV neurons in the neocortex of subjects with schizophrenia, but the effects of this alteration are unclear, because Kv9.3 subunit function is poorly understood. Therefore, to assess the role of Kv9.3 subunits in PV neuron function, we combined gene expression analyses, computational modeling, and electrophysiology in acute slices from the cortex of Kcns3-deficient mice. Kcns3 mRNA levels were ~ 50% lower in cortical PV neurons from Kcns3-deficient relative to wildtype mice. While silent per se, Kv9.3 subunits are believed to amplify the Kv2.1 current in Kv2.1-Kv9.3 channel complexes. Hence, to assess the consequences of reducing Kv9.3 levels, we simulated the effects of decreasing the Kv2.1-mediated current in a computational model. The FS cell model with reduced Kv2.1 produced spike trains with irregular inter-spike intervals, or stuttering, and greater Na+ channel inactivation. As in the computational model, PV basket cells (PVBCs) from Kcns3-deficient mice displayed spike trains with strong stuttering, which depressed PVBC firing. Moreover, Kcns3 deficiency impaired the recruitment of PVBC firing at gamma frequency by stimuli mimicking synaptic input observed during cortical UP states. Our data indicate that Kv9.3 subunits are critical for PVBC physiology and suggest that KCNS3 deficiency in schizophrenia could impair PV neuron firing, possibly contributing to deficits in cortical gamma oscillations in the illness.
Huntington's disease (HD) starts its pathology long before clinical manifestation, however, there is no therapy to cure it completely and only a few studies have been reported for delaying the progression of HD. Recently, it has been shown that heterochronic parabiosis can modulate the neurodegenerative diseases. Despite the importance of the transportation process of positive factors during heterochronic parabiosis, there were limited understandings because the transportation process is nanoscale, which makes it difficult to identify the messenger unit. We demonstrated that heterochronic parabiosis could modulate HD in R6/2 mice model, and identified the messenger unit for transferring positive factors in the young blood serum.
R6/2 mice were surgically connected with young wild-type mice (n=13), old wild-type mice (n=8), or R6/2 mice (n=6) to examine the effect of heterochronic parabiosis. Parabionts composed of 5- to 6-week-old transgenic and wild-type mice were observed for 6weeks in a single cage. Thhared blood circulation through heterochronic parabiosis, furthermore, we demonstrated that the exosomes could be messengers for transferring positive factors, showing the potential of exosomes from young blood for the amelioration of HD.
We found that the overall pathology of HD could be improved by the shared blood circulation through heterochronic parabiosis, furthermore, we demonstrated that the exosomes could be messengers for transferring positive factors, showing the potential of exosomes from young blood for the amelioration of HD.The completion-of-tumor hypothesis involved in the dynamic interplay between the initiating oncogenic event and progression is essential to better recognize the foundational framework of tumors. Here we review and extend the gametogenesis-related hypothesis of tumors, because high embryonic/germ cell traits are common in tumors. The century-old gametogenesis-related hypothesis of tumors postulated that tumors arise from displaced/activated trophoblasts, displaced (lost) germ cells, and the reprogramming/reactivation of gametogenic program in somatic cells. Early primordial germ cells (PGCs), embryonic stem (ES) cells, embryonic germ cells (EGCs), and pre-implantation embryos at the stage from two-cell stage to blastocysts originating from fertilization or parthenogenesis have the potential to develop teratomas/teratocarcinomas. In addition, the teratomas/teratocarcinomas/germ cells occur in gonads and extra-gonads. Undoubtedly, the findings provide strong support for the hypothesis. However, it was thought that these tumor types were an exception rather than verification.