Gene expression is a poor predictor of the metabolite abundance in cancer cells

Metabolic reprogramming is a hallmark of cancer characterized by global changes in metabolite levels. However, compared with the study of gene expression, profiling of metabolites in cancer samples remains relatively understudied. We obtained metabolomic profiling and gene expression data from 454 human solid cancer cell lines across 24 cancer types from the Cancer Cell Line Encyclopedia (CCLE) database, to evaluate the feasibility of inferring metabolite levels from gene expression data. For each metabolite, we trained multivariable LASSO regression models to identify gene sets that are most predictive of the level of each metabolite profiled. Even when accounting for cell culture conditions or cell lineage in the model, few metabolites could be accurately predicted. In some cases, the inclusion of the upstream and downstream metabolites improved prediction accuracy, suggesting that gene expression is a poor predictor of steady-state metabolite levels. Our analysis uncovered a single robust relationship between the expression of nicotinamide N-methyltransferase (NNMT) and 1-methylnicotinamide (MNA), however, this relationship could only be validated in cancer samples with high purity, as NNMT is not expressed in immune cells. Together, our findings reveal the challenge of inferring metabolite levels from metabolic enzyme levels and suggest that direct metabolomic profiling is necessary to study metabolism in cancer.

Reliability of Grip Strength as a Predictor of Hand Limitation Among U.S. Older Adults: How Good is Grip Strength?

Grip strength is commonly used to assess hand function in older adults and is associated with health outcomes including muscle strength, cognition, and mortality. However, the degree to which grip strength predicts an actual hand limitation is unknown. This study evaluated grip strength as a predictor of hand limitations associated with activities of daily living. Using the 2011-14 National Health and Nutrition Examination Survey (NHANES), we selected five self-reported hand-related functional limitations to classify older adults reporting one or more limitations versus those with no limitations. We identified 2,064 older adults (age≥65), 31% of whom reported a hand-related limitation. Odds ratios were used to assess the association between grip strength quartile and the likelihood of a hand limitation while controlling for sex, race/ethnicity, education level, income, and pain. Receiver operator curves were used to evaluate the degree to which grip strength discriminates between those with limitations versus those without. Older adults with very low grip strength (lowest quartile) were more likely to have at least one limitation (OR:6.1, 95% CI:3.2,11.8) than those with high grip strength (highest quartile). However, receiver operator curves suggested grip strength only modestly discriminated hand limitations (area under curve:0.71). While self-reported hand limitations were associated with lower grip strength, it was a relatively poor predictor of hand impairments among older adults. This study suggests grip strength may not predict hand function as well as previously thought. Better assessments are needed to adequately evaluate upper extremity impairments to help older adults maintain functional independence.

Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes become staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.

Correlation of ER PR receptors with other prognostic parameters of breast carcinoma

To study the MRM specimens for size, grade of the tumor, LVI and LN metastases and the ER/PR receptors of the tumor. To study the association of ER/PR status with the above mentioned prognostic parameters. This three-year study includes 72 histopathologically confirmed cases of carcinoma breast. The tumor type, grade, LNM, LVE were reported on H & E. The ER-PR study was done of all 72 cases. The tumor size, grade, LNM, LVE were correlated with receptor status. Out of 72 cases majority (53%) of cases were in 41-50 years of age group, and tumor size was between 2-4 cm in (54.16%) cases; majority were of grade II carcinoma (60%) of which 59% were ER-PR positive. Out of 46 cases with negative LNM and LVE, 30 cases (65%) were ER-PR positive. In our observation there is no association between higher histological grade and ER-PR status. No obvious correlation with tumor size was noted. But increase in tumor size could also be a poor predictor of ER-PR status. LNM, LVE is poor predictor of ER-PR status.

DETERMINATION OF DIAGNOSTIC ACCURACY OF BIOCHEMICAL PARAMETERS (CRP, LDH & FERRITIN) IN THE DIAGNOSIS OF COVID-19 IN SUSPECTED COVID CASES

Objective: To determine the diagnostic accuracy of the Lactate Dehydrogenase, C-Reactive Protein and Ferritin in suspected patients of COVID-19. Study Design: Cross-sectional validation study. Place and Duration of Study: Pathology department of Combined Military Hospital Lahore in the month of May 2020. Methodology: We included 101 adult (>18 years) symptomatic suspected COVID-19 patients of both genders. Children, pregnant women and asymptomatic patients were excluded from study. Age, gender and results of Reverse Transcriptase Polymerase Chain Reaction, Lactate Dehydrogenase, C-Reactive Protein, ferritin were recorded. Results: Lactate Dehydrodenase had highest sensitivity (75%) with positive predictive value of 71.6% and diagnostic accuracy of 65.3% among three biochemical parameters studied. Receiver Operator Characteristic curve was studied. Area under curve of Lactate Dehydrogenase (AUC=0.65) and Ferritin (AUC=0.59) reflected their ability to prognosticate the presence of COVID19 disease. However, C-Reactive Protein (AUC=0.42) appeared to be a poor predictor of the disease. Conclusion: Raised serum Lactate Dehydrogenase (>490 U/L) and Ferritin (>152 ng/L) levels can be used to predict the Reverse Transcriptase Polymerase Chain Reaction positivity for COVID-19 in the population of suspected patients of COVID19. However, C-Reactive Protein is a poor predictor of COVID-19.

Assessment of the prognostic impact of serum level of soluble cluster of differentiation (sCD155) in newly diagnosed Low grade cell Non Hodgjen Lymphoma in Adult Egyptian patients

Background CD155-dependent signals not only influenced net tumor growth but also responsiveness to immune checkpoint therapies. Thus, blocking CD155 could be a rational strategy to improve current immunotherapeutic Aim of the work To assess CD155 in newly diagnosed Low grade B non Hodgkin Lymphomas as prognostic marker for remission Patients and methods CD 155 measured by Ellisa at the time of diagnosis of 50 patients newly diagnosed low grade B non Hodgjen Lymphomas and the remission status followed up prospectively at 3 and 6 months in hematology unit at Ain Shams University Hospital Results there were high statistically significant difference between CD155 level and cytogenetic risk and Eligibility for auto transplantation, there were statistically significant difference between CD155 level and B symptoms, there were high statistically significant difference between CD155 level and Radiology stage, BM infiltation, protocol after 3months, There were high statistically significant difference between CD155 level and Radiology stage, BM infiltration, CBC after 6 months There were high statistically significant difference between CD155 level and non Remission and CD155 had Sensitivity88.46% and Specificity75% as poor predictor of remission Conclusion The CD155 level is prognostic factors for remission in Low grade B non Hodgkin Lymphomas as high CD155 level is poor prognostic factors for response and remission with Sensitivity 88.46%and Specificity75. %

The measure of spatial position within groups that best predicts predation risk depends on group movement

Both empirical and theoretical studies show that an individual's spatial position within a group can impact the risk of being targeted by predators. Spatial positions can be quantified in numerous ways, but there are no direct comparisons of different spatial measures in predicting the risk of being targeted by real predators. Here, we assess these spatial measures in groups of stationary and moving virtual prey being attacked by three-spined sticklebacks ( Gasterosteus aculeatus ). In stationary groups, the limited domain of danger best predicted the likelihood of attack. In moving groups, the number of near neighbours was the best predictor but only over a limited range of distances within which other prey were counted. Otherwise, measures of proximity to the group's edge outperformed measures of local crowding in moving groups. There was no evidence that predators preferentially attacked the front or back of the moving groups. Domains of danger without any limit, as originally used in the selfish herd model, were also a poor predictor of risk. These findings reveal that the collective properties of prey can influence how spatial position affects predation risk, via effects on predators' targeting. Selection may therefore act differently on prey positioning behaviour depending on group movement.

Correlation ER/PR status of Breast Carcinoma with Tumor size, Tumor grade, Lymphovascular emboli, Lymph node metastasis and the distant metastasis

Breast cancer is the most frequent cancer in females in the world and is the second most common cancer in India after cervical cancer. The breast cancer is second most common reason of loss of existence in each developed and additionally most of the growing countries. For the appraisal of prognosis of breast cancer commonly followed is the NOTTINGHAM PROGNOSTIC INDEX (NPI) which includes- tumor size, histological tumor grade, lymph node metastasis and hormone receptor status. These prognostic component help in administration and therapeutic requirement of breast cancer patient.1. To study the MRM specimens for size, grade of the tumor, LVI and LN metastases and the ER/PR receptors of the tumor. 2.To study the association of ER/PR status with the above mentioned prognostic parameters.This three-year study includes 50 histopathologically confirmed cases of carcinoma breast. The tumor type, grade, LNM, LVE were reported on H & E. The ER-PR study was done of all 50 cases. The tumor size, grade, NM, LVE were correlated with receptor status. Out of 50 cases majority (7.5%) of cases were in 41-50 years of age group, and tumor size was between 2-4 cm in (17.5%) cases; majority were of grade II carcinoma (17.5%) of which 13% were ER-PR positive. Out of 35 cases with negative LNM and LVE, 26 cases (13%) were ER-PR positive.In our observation there is no association between higher histological grade and ER-PR status. No obvious correlation with tumor size was noted. But increase in tumor size could also be a poor predictor of ER-PR status. LNM, LVE is poor predictor of ER-PR status.