Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers

The dysregulation of mRNA translation is common in malignancies and may lead to tumorigenesis and progression. Eukaryotic initiation factor 4A (eIF4A) proteins are essential for translation, exhibit bidirectional RNA helicase function, and act as RNA-dependent ATPases. In this review, we explored the predicted structures of the three eIF4A isoforms (eIF4A1, eIF4A2, and eIF4A3), and discussed possible explanations for which function during different translation stages (initiation, mRNA localization, export, and mRNA splicing). These proteins also frequently served as targets of microRNAs (miRNAs) or long noncoding RNAs (lncRNAs) to mediate epithelial-mesenchymal transition (EMT), which was associated with tumor cell invasion and metastasis. To define the differential expression of eIF4A family members, we applied the Tumor Immune Estimation Resource website. We figured out that the eIF4A family genes were differently expressed in specific cancer types. We also found that the level of the eIF4A family genes were associated with abundant immune cells infiltration and tumor purity. The associations between eIF4A proteins and cancer patient clinicopathological features suggested that eIF4A proteins might serve as biomarkers for early tumor diagnosis, histological classification, and clinical grading/staging, providing new tools for precise and individualized cancer treatment.

ASSESSMENT OF LYMPHEDEMA WITH LYMPHOSCINTIGRAPHY: CAN NODAL QUANTIFICATION HELP?

Lymphoscintigraphy with combined qualitative and quantitative analysis is reported to be a more sensitive approach to diagnose lymphedema in comparison with the conventional clinical analysis. Our study seeks to evaluate the diagnostic performance of lower limb lymphoscintigraphy with amalgamation of qualitative and quantitative analysis by measuring the ilio-inguinal nodal uptake. This prospective observational study was comprised of 86 patients (172 limbs) diagnosed with lower limb lymphedema. After a thorough clinical grading of edema, radionuclide lymphoscintigraphy was performed as per a dedicated institutional protocol. Ilio-inguinal nodal quantification of tracer uptake was computed along with the visual study of the scans. Additionally, the corresponding mean nodal uptake percentage for each grade of lymphedema was assessed and a cut off nodal uptake percentage to differentiate between normal and abnormal limbs was defined. Although quantitative analysis with nodal uptake percentage provides objective criteria to diagnose lymphedema, it can only act as an adjunct to qualitative method without replacing it. Finally, standardization of procedure for quantitative lymphoscintigraphy is needed including the potential for combining both rate of clearance of tracer from injection site and nodal uptake for quantification.

Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study

ObjectiveThe aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer.MethodsA prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI).ResultsRisk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading.ConclusionApparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a ‘gold standard’ method when addressing lymphedema for determining risk factors.

The value of arterial spin labeling imaging in the classification and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy

Objective: This study aims to investigate the correlation between cerebral blood flow (CBF) values and neonatal behavioral neurological assessment (NBNA) in hypoxic-ischemic encephalopathy (HIE), the relationship between early CBF value changes and the prognosis of neonatal HIE, and the consistency between the clinical grading and magnetic resonance (MR) grading of HIE. Methods: Forty neonates with HIE were scanned using the three-dimensional arterial spin labeling (ASL) sequencing of the cranial magnetic resonance imaging (MRI). These newborns were classified as having mild, moderate and severe HIE, according to the clinical grading, and as being normal or having mild, moderate, or severe HIE, according to the MRI grading. Then, the consistency of these two grading systems were compared. Afterwards, the differences in the CBF values of neonates in groups with mild, moderate and severe HIE were compared. In addition, these neonates were grouped according to their NBNA scores. A score of ≥35 was considered a good prognosis, while a score of ≤35 was considered a poor prognosis. The differences in CBF values between these two groups were compared, and the correlation between the CBF values and NBNA scores was determined. Results: There was a strong consistency between the evaluation results for the clinical grading and MR grading (kappa value = 0.672, P<0.001). The differences in CBF values for the basal ganglia (BG) area and thalamus, and the differences in NBNA scores for groups with mild, moderate, or severe HIE were statistically significant (P<0.05). The differences between the poor prognosis group and good prognosis group, in terms of the CBF values for the BG area and thalamus, and the NBNA scores, were statistically significant (P<0.05). The CBF values in the BG region and thalamus were closely and negatively correlated with the NBNA scores. Conclusion: Early CBF values in the BG area and thalamus can objectively and visually reflect the severity of the HIE, and be used to predict the outcome of functional brain damage, allowing early neuroprotective treatment to be initiated. The higher the perfusion in the BG region and thalamus, the lower the NBNA score, and the worse the prognosis would likely be. ASL combined with the NBNA score provides a more comprehensive classification for HIE and a more accurate assessment of the clinical prognosis, providing more medical imaging information for early clinical treatment.

Systemic and local immune response to intraocular AAV vector administration in non-human primates

The positive clinical outcomes in adeno-associated virus (AAV)-mediated retinal gene therapy have often been attributed to the low immunogenicity of AAVs along with the immune-privilege of the eye. However, several recent preclinical studies and clinical trials have shown potential for inflammatory responses to AAV mediated gene therapy. Our current understanding of the factors contributing to intraocular inflammation such as the existence of serum antibodies against AAVs prior to injection and their contribution to increases in antibody levels post-injection is incomplete. The parameters that regulate the generation of new antibodies in response to the AAV capsid or transgene post-injection after intraocular administration are also insufficiently described. In this study we carried out a retrospective analysis of the pre-existing serum antibodies in correlation with changes in antibody levels after intraocular injections of AAV in non-human primates (NHPs). We analyzed NHP serums for the presence of both Binding Antibodies (BABs), as well as a subset of these called Neutralizing Antibodies (NABs) that impede AAV transduction upon binding. We observed significantly higher pre-existing serum BABs against AAV8 compared to other serotypes. We observed a dose-dependent increase in both BABs and NABs in the serums collected post-injection, irrespective of the serotype or the mode of injection. Lastly, we were able to demonstrate a co-relation between the serum BAB levels with clinical grading of inflammation and levels of transgene expression.

Correlation of Vitamin D Level with Electrophysiological Findings and Clinical Grading in Carpal Tunnel Syndrome

Carpal tunnel syndrome is a neurological disease that presented with paresthesias, pain, and numbness in the hand's median nerve compression. Vitamin D was assumed to affect both electrophysiological &clinical gradings, the study aims to assess the correlation between the deficiency of vitamin D and both electrophysiological and clinical gradings. This study was conducted in Ghazi Alhariri Hospital during the period from the first of November/2020 to the twenty-eighth of February/2021, fifty five individuals were referred to as Carpal tunnel syndrome patients, and compared to (55) control individuals, blood samples were withdrawn from the patients (3ml), centrifuged and kept in the freezer (-20°C) until the time of analysis of vitamin D3, Sensory and motor nerve conduction studies of both median and ulnar nerve were done bilaterally. patients were classified electrophysiologically and clinically into two subgroups (mild to moderate) and (severe) groups. The result showed that the differences are not significant in the gender, BMI and vitamin D of the patients versus the control group (p>0.05), the difference of the electrophysiological parameters was not significant between patients with low vitamin D versus those with normal vitamin D (p value>0.05), there was a significant association between the electrophysiological and clinical grading in addition to a significant association between vitamin D level and the clinical grading. Vitamin D deficiency does not affect the electrophysiological parameters while the clinical grading becomes worse with the decrease in its level. The electrophysiological grading is associated with clinical grading.

A novel multiple subdivision-based algorithm for quantitative assessment of retinal vascular tortuosity

Vascular tortuosity as an indicator of retinal vascular morphological changes can be quantitatively analyzed and used as a biomarker for the early diagnosis of relevant disease such as diabetes. While various methods have been proposed to evaluate retinal vascular tortuosity, the main obstacle limiting their clinical application is the poor consistency compared with the experts’ evaluation. In this research, we proposed to apply a multiple subdivision-based algorithm for the vessel segment vascular tortuosity analysis combining with a learning curve function of vessel curvature inflection point number, emphasizing the human assessment nature focusing not only global but also on local vascular features. Our algorithm achieved high correlation coefficients of 0.931 for arteries and 0.925 for veins compared with clinical grading of extracted retinal vessels. For the prognostic performance against experts’ prediction in retinal fundus images from diabetic patients, the area under the receiver operating characteristic curve reached 0.968, indicating a good consistency with experts’ predication in full retinal vascular network evaluation.