Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer.

Despite advances in the diagnosis and treatment of colorectal cancer (CRC), it remains a major cause of cancer related death globally. There are currently no chemotherapeutic agents that have been found to eradicate the disease without adverse effects. A defect in the death receptor signaling pathway is a feature of CRC. The ligand of these receptors belongs to the tumor necrosis factor family, and that are particularly expressed by cells of the immune system, and that induce apoptosis in a caspase dependent manner. The fact that malignant cells are particularly sensitive to these ligands, compared to normal cells, has led to work on the assessment of compounds that activate this pathway in the treatment of CRC. Phase I trials have shown that these death receptor agonists are safe. Phase II and III trials are currently investigating the efficacy of these therapeutic agents in the treatment of CRC. In this review, we describe the biochemical death receptor signaling pathway and its relationship to CRC. We also summarize the current clinical studies that are targeting this signaling pathway in CRC treatment.

Comparative analysis of risk factors for retinopathy of prematurity in single and multiple birth neonates.

AIM: To conduct a comparative analysis of risk factors for retinopathy of prematurity (ROP) in single- and multiple-born neonates. METHODS: In a retrospective evaluation of 521 premature neonates, encompassing singletons, twins, and triplets born at or before 34 weeks of gestational age with a birthweight of less than 2000 g and who completed the ROP screening program, between 2020 and 2023, in outpatient referral ROP screening clinic affiliated by Shiraz University of Medical Sciences, were included. Neonates with the eligibility criteria were enrolled in the screening program from 28 days old age and followed up to discharge or treatment based on national ROP screening guideline. Data on ROP severity, outcome, treatment modality, and risk factors, including gestational age (GA), birth weight (BW), sex, duration of neonatal intensive care unit (NICU) admission, oxygen supplementation, mechanical ventilation, blood transfusion, method of delivery, and maternal and neonatal comorbidities, were extracted and compared between premature neonates from singleton and multiple births. RESULTS: The analysis of the ROP severity distribution revealed 238 neonates (45.7%) with low-risk (type 2 prethreshold ROP or less severe) ROP and 16 (3.1%) with high-risk (type I prethreshold ROP or more severe) ROP who underwent treatment. According to the comparative analysis of risk factors in neonates with ROP requiring treatment, multiple birth neonates exhibited significantly greater GA (27.50 ± 3.27 vs. 30.00 ± 2.00 vs. 31.14 ± 0.38 weeks, p = 0.032 for singletons, twins and triplets, respectively); greater BW (861.67 ± 274.62 vs. 1233.33 ± 347.75 vs. 1537.14 ± 208.86 g, p = 0.002); and shorter duration of NICU admission (60.17 ± 21.36 vs. 34.00 ± 12.17 vs. 12.00 ± 6.32 days, p = 0.001) and oxygen supplementation (47.33 ± 16.57 vs. 36.00 ± 8.49 vs. 4.60 ± 2.41 days, p = 0.001). There was no significant difference between single-born neonates and multiple-born neonates regarding the prevalence of other risk factors. Multiple-born neonates with no ROP and low risk ROP showed significantly lower GA and BW compared to singletons (p < 0.001). CONCLUSION: Multiple gestation neonates may develop high-risk ROP requiring treatment at a greater gestational age and birth weight and at a lower duration of oxygen supplementation and NICU admission compared to the single birth neonates. This pattern prompts a reevaluation of screening criteria, suggesting a potential need to consider multiple birth neonates with lower traditional risk factors in screening programs. This pattern should be further evaluated in larger populations of multiple born premature neonates.

Congenital narrowing of a pulmonary vein: slit-like pulmonary vein ostium.

We report the case of a 60-year-old female with a history of refractory paroxysmal atrial fibrillation. Preablation contrast enhanced pulmonary vein computed tomography (CT) scan demonstrated a slit-like narrowing of the left inferior pulmonary vein ostium. The narrowing measured approximately 3 mm, with poststenotic dilation. The patient had no prior history of ablation. The patient subsequently underwent segmental antral isolation of all four pulmonary veins and cavo-tricuspid isthmus ablation with bidirectional block. The diagnosis of preexisting congenital pulmonary vein stenosis had an impact on the type of ablation procedure performed (antral rather than ostial) and will affect the interpretation of postablation CT scans.

A Bayesian-based classification framework for financial time series trend prediction.

Financial time series have been extensively studied within the past decades; however, the advent of machine learning and deep neural networks opened new horizons to apply supercomputing techniques to extract more insights from the underlying patterns of price data. This paper presents a tri-state labeling approach to classify the underlying patterns in price data into up, down and no-action classes. The introduction of a no-action state in our novel approach alleviates the burden of denoising the dataset as a preprocessing task. The performance of our labeling algorithm is experimented with using machine learning and deep learning models. The framework is augmented by applying the Bayesian optimization technique for the selection of the best tuning values of the hyperparameters. The price trend prediction module generates the required trading signals. The results show that the average annualized Sharpe ratio as the trading performance metric is about 2.823, indicating the framework produces excellent cumulative returns.

Lower iodine load in routine contrast-enhanced CT: an alternative imaging strategy.

OBJECTIVE: To demonstrate an alternative imaging strategy for routine thoracic computed tomography using low intravenous contrast volume. METHODS: Based on radiologists' clinical judgment, 61 thoracic computed tomographic examinations were performed using 15 mL of iohexol intravenous contrast. Indications included patients with relative con traindications to contrast, American College of Radiology appropriateness rating of 1 to 6 for contrast, rating of 7 or greater for contrast with a modifying condition, and cases without specific rating in which contrast may have been useful although not mandatory. Images were retrospectively reviewed to determine adequacy as part of an American Board of Radiology Practice Quality Improvement project. Ascending aorta and right and left pulmonary artery enhancement was measured and compared to most recent routine contrast protocol examination if available. RESULTS: All studies were adequate for evaluation of the given indication. Degree of vascular opacification was sufficient for discriminating between mediastinal structures. Computed tomography number (Hounsfield units) ± standard deviation using 15 mL of contrast compared to routine protocol was 134 ± 47.8 and 240.8 ± 86.6 in ascending aorta, 109.6 ± 47.6 and 185 ± 59.3 in right pulmonary artery, and 112 ± 50 and 186 ± 56.3 in left pulmonary artery, respectively. Mean difference in computed tomography number was significant. Low contrast dose studies demonstrated relatively decreased soft tissue enhancement. CONCLUSIONS: The 15-mL protocol results in reduced vascular and soft tissue enhancement; however, reasonable-quality images are obtained that are diagnostic for a wide range of indications, namely, those involving thoracic inlet, mediastinal, and hilar structures.

Spatio-temporal analysis and determination of the ecological niche model of Giardia Lamblia (Lambl, 1859) in Ardabil province, northwestern Iran.

Intestinal parasites have a serious health problem and frequently infect children in poor urban areas in developing countries. Some types of Cryptosporidium, Entamoeba and Giardia are amongst the most prevalent ones. The aim of this study was explore the distribution pattern of intestinal parasites and the ecological niche of Giardia lamblia in Ardabil Province. This was retrospective cross-sectional study, the officially registered statistics of health centers and hospitals in Ardabil University of Medical Sciences from January 2017 to December 2019 were used. The Kriging interpolation analysis was run to detect the high-risk areas of the disease in the province (P < 0.05) by ArcGIS10.4.1 and to construct the ecological niche model of the G.lamblia parasite, analyzed by Maxent3.3 software. Totally of 238 cases of intestinal parasite were reported during the study period, 77.7% of which were males and 22.3% females. Seven types of intestinal parasites were prevalent with G.lamblia species (79.4%) being the most and Entamoeba histolytica species (4%) the least prevalent one. There was one hotspot in the province in the center with an incidence risk of 41-45.5%. The most important climate and environmental factors affecting the ecological niche of G.lamblia are Bio16, Bio3, and the NDVI. G.lamblia is the most prevalent intestinal parasite in Ardabil Province; moreover, one important hotspots was also detected in the province that can provide useful information regarding the management and control of this parasite.

A quantitative approach to sequence and image weighting.

Weighting is the term most frequently used to describe magnetic resonance pulse sequences and the concept most commonly used to relate image contrast to differences in magnetic resonance tissue properties. It is generally used in a qualitative sense with the single tissue property thought to be most responsible for the contrast used to describe the weighting of the image as a whole. This article describes a quantitative approach for understanding the weighting of sequences and images, using filters and partial derivatives of signal with respect to logarithms of tissue property values. Univariate and multivariate models are described for several pulse sequences including methods for maximizing weighting and calculating both sequence and image weighting ratios. The approach provides insights into difficulties associated with qualitative use of the concept of weighting and a quantitative basis for assessing the signal, contrast, and weighting of commonly used sequences and images.

Comparison of amoxicillin and metronidazole effect on three-drug regimen for the treatment of Helicobacter pylori infection in children.

Helicobacter pylori is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Three-drug regimen is the first-line treatment for this infection, but the response rate to treatment varies in different geographical regions. This study was conducted to comparatively determine the effect of amoxicillin and metronidazole on three-drug regimen to treat H. pylori infection in 1-15-year-old children. This clinical trial was conducted on 82 patients aged 1-15 years with convenience sampling referring to the Endoscopy Unit of Hajar Hospital, Shahrekord. Group 1 was administered with clarithromycin, amoxicillin, and omeprazole (CAO), and Group 2 with, clarithromycin, metronidazole, and omeprazole (CMO). One month after completion of the treatment, stool antigen test was used to study the eradication of H. pylori. Data were analyzed using SPSS software by Chi-square test. Three of the 82 patients were excluded from the study because of side effects caused by drugs. Nearly 87.2% of the patients in CAO-treated group and 92.5% in CMO-treated group had response to treatment. There was no significant difference in eradication rate between the two regimens (P = 0.43). The two regimens displayed no superiority over each other for eradicating H. pylori infection and response rate to treatment in children aged 1-15 years.

Prevalence of hepatitis B virus precore stop codon mutations in chronically infected children.

AIM: To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS: We investigated a large pediatric population of 155 European children (mean age 10.9 years) with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS: Seventy-four (48%) of the sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A. In the group of 90 HBeAg positive patients, 2 (2.2%) 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants. The difference was not statistically significant (P = 0.13). CONCLUSIONS: HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.

Anatomy and pathology of the eye: role of MR imaging and CT.

Since the development of CT and MR imaging, significant progress has been made in ophthalmic imaging. As the technology advanced and MR imaging units improved their ability in term of spatial resolution, the role of MR imaging in ophthalmic imaging has increased accordingly. This article considers the role of MR and CT imaging in the diagnosis of selected pathologies of the eye.

Dorsal Scapular Artery Variations and Relationship to the Brachial Plexus, and a Related Thoracic Outlet Syndrome Case.

Rationale Knowledge of the relationship of the dorsal scapular artery (DSA) with the brachial plexus is limited. Objective We report a case of a variant DSA path, and revisit DSA origins and under-investigated relationship with the plexus in cadavers. Methods The DSA was examined in a male patient and 106 cadavers. Results In the case, we observed an unusual DSA compressing the lower plexus trunk, that resulted in intermittent radiating pain and paresthesia. In the cadavers, the DSA originated most commonly from the subclavian artery (71%), with 35% from the thyrocervical trunk. Nine sides of eight cadavers (seven females) had two DSA branches per side, with one branch from each origin. The most typical DSA path was a subclavian artery origin before passing between upper and middle brachial plexus trunks (40% of DSAs), versus between middle and lower trunks (23%), or inferior (4%) or superior to the plexus (1%). Following a thyrocervical trunk origin, the DSA passed most frequently superior to the plexus (23%), versus between middle and lower trunks (6%) or upper and middle trunks (4%). Bilateral symmetry in origin and path through the brachial plexus was observed in 13 of 35 females (37%) and 6 of 17 males (35%), with the most common bilateral finding of a subclavian artery origin and a path between upper and middle trunks (17%). Conclusion Variability in the relationship between DSA and trunks of the brachial plexus has surgical and clinical implications, such as diagnosis of thoracic outlet syndrome.

Orbital and ocular imaging using 3- and 1.5-T MR imaging systems.

The goal of this article is to familiarize general radiologists and clinicians (particularly ophthalmologists, neuro-ophthalmologists, neurologists, and neurosurgeons) with the recent introduction of clinical MR imaging scanners operating at a magnetic field strength of 3-T and to compare them with the more common standard scanners operating at 1.5-T. In this study, MR imaging at 3-T was found to offer superior depiction of orbital and intracranial anatomy and pathologic findings. Spin echo, high spatial resolution, T2-weighted, thin-section MR imaging sequences are especially useful and sensitive at 3-T for the evaluation of orbital, ocular, and intracranial anatomy and pathologic findings. The authors din that time-of-flight (TOF) MR angiography at 3-T surpasses the best MR angiography at 1.5-T and that two-dimensional TOF venography and three-dimensional contrast MR venography at 3-T offer superior visualization of intracranial and facial veins as compared with MR venography at 1.5-T. We believe that with further quality image production and efficient coil design, 3-T MR imaging should hold the promise of playing an important role in the diagnostic imaging evaluation of ocular, orbital, and optic pathway pathologic findings.

Anatomy and pathology of the eye: role of MR imaging and CT.

Since the development of CT and MR imaging, significant progress in ophthalmic imaging has been made. As the technology advanced and MR imaging units improved their ability in terms of spatial resolution, the role of MR imaging in ophthalmic imaging has increased accordingly. This article considers the role of MR and CT imaging in the diagnosis of selected pathologies of the eye.

A large cardiac mass: diagnosis of caseous mitral annular calcification and determining optimum management strategy.

A 64-year-old woman with dizziness and blurry vision underwent an evaluation for a possible stroke with a head-neck CT scan and a transthoracic echocardiogram. The head-neck CT scan was unremarkable, but the echocardiogram was notable for a 2.0 × 2.3 cm heterogeneous echodensity attached to the mitral valve. After a transesophageal echocardiogram and chest CT scan, the mass was determined to be a caseous mitral annular calcification, CMAC. This entity is a rare variant of MAC with an estimated prevalence of 0.068%. Echocardiographic techniques can distinguish CMAC from other intracardiac masses such as tumor, cyst, or abscess. CMAC is associated with cerebrovascular accidents; however, optimal treatment is controversial given the rarity of this clinical finding. Management strategies should be tailored based on the patient's presentation, risk factors, and overall clinical circumstances.

Rationale and design of the ViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) trial.

BACKGROUND: Coronary CT angiography (CTA) has emerged as an effective noninvasive method for direct visualization of the coronary arteries, with high diagnostic performance compared with invasive coronary angiography (ICA). However, coronary CTA is prone to artifacts, including coronary motion, which may reduce its diagnostic performance. Intracycle motion compensation algorithms (MCAs) from a combination of software and hardware techniques now allow for correction of coronary motion, but the diagnostic performance of MCAs compared with traditional coronary CTA reconstruction methods remains unexplored. METHODS: ViCTORY (Validation of an Intracycle CT Motion CORrection Algorithm for Diagnostic AccuracY) is a prospective international multicenter trial of 218 patients which is designed to evaluate the performance of MCAs for the diagnosis of anatomically obstructive coronary artery disease (CAD) compared with an ICA reference standard, on a per-patient, per-vessel, and per-segment basis. Patients enrolled into ViCTORY will undergo investigational coronary CTA and clinically indicated ICA and will not receive heart rate-lowering medications before coronary CTA. Coronary CTA images will be reconstructed by conventional standard methods as well as by MCAs. Blinded core laboratory interpretation will be performed for coronary CTA and ICA in an intent-to-diagnose fashion. RESULTS: The primary end point of ViCTORY is the per-patient diagnostic accuracy of MCAs for the diagnosis of anatomically obstructive CAD compared with ICA. Secondary end points will include other per-patient, per-vessel, and per-segment diagnostic performance characteristics, including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Other key secondary end points will include diagnostic interpretability, image quality, the upper heart rate threshold of utility of MCAs, and the additive value of MCAs to traditionally reconstructed coronary CTA. CONCLUSION: ViCTORY will determine whether MCAs improve the diagnosis of obstructive CAD in patients undergoing coronary CTA who are not receiving heart rate-lowering medications.

Automated vessel segmentation using cross-correlation and pooled covariance matrix analysis.

Time-resolved contrast-enhanced magnetic resonance angiography (CE-MRA) provides contrast dynamics in the vasculature and allows vessel segmentation based on temporal correlation analysis. Here we present an automated vessel segmentation algorithm including automated generation of regions of interest (ROIs), cross-correlation and pooled sample covariance matrix analysis. The dynamic images are divided into multiple equal-sized regions. In each region, ROIs for artery, vein and background are generated using an iterative thresholding algorithm based on the contrast arrival time map and contrast enhancement map. Region-specific multi-feature cross-correlation analysis and pooled covariance matrix analysis are performed to calculate the Mahalanobis distances (MDs), which are used to automatically separate arteries from veins. This segmentation algorithm is applied to a dual-phase dynamic imaging acquisition scheme where low-resolution time-resolved images are acquired during the dynamic phase followed by high-frequency data acquisition at the steady-state phase. The segmented low-resolution arterial and venous images are then combined with the high-frequency data in k-space and inverse Fourier transformed to form the final segmented arterial and venous images. Results from volunteer and patient studies demonstrate the advantages of this automated vessel segmentation and dual phase data acquisition technique.

Atresia de orificio del seno coronario con vena cava superior izquierda persistente / Atretic coronary sinus orifice with a persistent left superior vena cava

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