Brain Cancer Prediction Based on Novel Interpretable Ensemble Gene Selection Algorithm and Classifier.

The growth of abnormal cells in the brain causes human brain tumors. Identifying the type of tumor is crucial for the prognosis and treatment of the patient. Data from cancer microarrays typically include fewer samples with many gene expression levels as features, reflecting the curse of dimensionality and making classifying data from microarrays challenging. In most of the examined studies, cancer classification (Malignant and benign) accuracy was examined without disclosing biological information related to the classification process. A new approach was proposed to bridge the gap between cancer classification and the interpretation of the biological studies of the genes implicated in cancer. This study aims to develop a new hybrid model for cancer classification (by using feature selection mRMRe as a key step to improve the performance of classification methods and a distributed hyperparameter optimization for gradient boosting ensemble methods). To evaluate the proposed method, NB, RF, and SVM classifiers have been chosen. In terms of the AUC, sensitivity, and specificity, the optimized CatBoost classifier performed better than the optimized XGBoost in cross-validation 5, 6, 8, and 10. With an accuracy of 0.91±0.12, the optimized CatBoost classifier is more accurate than the CatBoost classifier without optimization, which is 0.81± 0.24. By using hybrid algorithms, SVM, RF, and NB automatically become more accurate. Furthermore, in terms of accuracy, SVM and RF (0.97±0.08) achieve equivalent and higher classification accuracy than NB (0.91±0.12). The findings of relevant biomedical studies confirm the findings of the selected genes.

Theoretical investigation of unsteady MHD flow within non-stationary porous plates.

Porous-permeable structures with magnetohydrodynamics (MHD) flow have a lot of applications in various disciplines of engineering. Transport of ferro-fluid in magnetic field has attained more focus in recent years. In this work, an analysis is accomplished to investigate the MHD transport of in-compressible viscid ferro-fluid (electrically conductive) amid two movable porous-permeable plates (PPP). Here asymptotic method is then selected to solve the model. In this study, the effects of diverse considerable parameters and constraints like surface permeability, Reynold's factor, and Hartmann's factor are elaborated in details.

Indoleamine 2,3-dioxygenase and regulatory t cells in intestinal mucosa in children with inflammatory bowel disease.

Impaired immune regulation has been suggested as an underlying mechanism of inflammatory bowel disease. Indoleamine 2,3-dioxygenase (IDO) and regulatory T cells expressing FOXP3 are crucial elements of immune regulation. Conversion of FOXP3- lymphocytes to Tregs is one of the functions of IDO. The aim of this study was to evaluate the number of cells expressing FOXP3 and IDO in the lamina propria of intestinal mucosa and to evaluate correlations between these parameters and disease activity. Sixty-six children newly diagnosed with inflammatory bowel disease (41 patients with ulcerative colitis and 25 patients with Crohn’s disease) were included in the study. Clinical activity of the disease was assessed by the Pediatric Ulcerative Colitis Activity Index and the Pediatric Crohn’s Disease Activity Index. Histopathological activity was scored according to the system described by Geboes. The infiltration of FOXP3+ and IDO+ cells was evaluated by immunohistochemistry. Sixteen patients with a diagnosis of irritable bowel syndrome (IBS) served as a control group. Lamina propria demonstrated a significantly higher infiltration of FOXP3+ and IDO+ cells in inflammatory bowel disease compared to the control group (p=0.001, p=0.004, respectively). The number of IDO+ and FOXP3+ cells correlated with clinical and histopathologic activity of Crohn’s disease. A positive correlation between the number of IDO+ and FOXP3+ cells was found in both types of inflammatory disease but not in patients with IBS. We conclude that indoleamine dioxygenase and FOXP3+ cells are upregulated in the intestinal mucosa of children with inflammatory bowel disease. IDO mediated conversion of FOXP3 -T cells to Tregs predominantly occurs in inflammation.

Can preschool-aged children swallow several minitablets at a time? Results from a clinical pilot study.

Minitablets are a novel, multi-compartment solid drug formulation, particularly intended for children between 1 and 6 years of age. Available literature shows that even infants are capable of swallowing a single minitablet. In this study, we have explored the level of acceptance of minitablets administered in units of 5 or 10. A group of thirty two 2-year-old children (2-years) and twenty eight 3-year-old children (3-years) have been enrolled in the study. Each child was asked to swallow placebo minitablets (2mm or 3mm) suspended in a fruity jelly on a spoon. The swallowing of minitablets (with or without chewing) was registered for 75% of 2-year-olds and for 93% of 3-year-olds. Moreover, most of the children (57% of all participants) were fully capable of swallowing all units without chewing (2-years: 50%; 3-years: 64%). However, no statistically significant differences in the swallowing ability were observed in gender and age groups. None of the children choked. Neither the number, nor the diameter of the administered minitablets have significantly influenced the ability to swallow units. The results show that minitablets administered in several units mixed with jelly food are safe and could be accepted by a pediatric population.

Embolization of portosystemic shunt for treatment of recurrent hepatic encephalopathy.

Hepatic encephalopathy in the setting of advanced chronic liver disease, occurs following a precipitating factor and generally responds to correction of the precipitating factor and anticoma measures. We report the case of a lady with Child A cirrhosis who presented with frequent episodes of hepatic encephalopathy without any precipitating factors. She was found to be having a large portosystemic shunt. The shunt was obliterated by coil embolotherapy following which there was no further episodes of encephalopathy.

Cardiovascular and hormonal responses to static handgrip in young and older healthy men.

The purpose of this study was to investigate the effect of age on cardiovascular changes and plasma concentrations of adrenomedullin (ADM), catecholamines, endothelin-1 (ET-1) and plasma renin activity (PRA) in healthy men. A total of 15 young (21 ± 0.3 years) and 15 older (64 ± 0.7 years) healthy men performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand without any break between the bouts. During exercise heart rate (HR), blood pressure (BP), stroke volume (SV) and pre-ejection period (PEP) and left ventricle ejection time (LVET) were measured. Blood samples were taken before exercise, at the end of both exercise bouts and in the fifth minute of the recovery period. The handgrip-induced increases in HR and cardiac output were significantly smaller in older than in young men (p < 0.01). SV decreased only in older men (p < 0.001). There were no differences between groups in BP increases. The baseline plasma ADM and catecholamines were higher in older man compared to young subjects. Handgrip caused increases in plasma ADM, ET-1 and PRA only in older men (p < 0.05). The increases in plasma ADM correlated positively with those of noradrenaline (NA), PRA, ET-1 and LVET and negatively with changes in total peripheral resistance (TPR), SV, PEP and PEP/LVET ratio. The increases in plasma ET-1 correlated positively with those of NA, PRA, TPR, mean BP and SV. These results revealed that ADM, ET-1 and angiotensin II can contribute to maintain vascular tone during static exercise in older but not in younger men.

Metabolic and hormonal responses to body carbohydrate store depletion followed by high or low carbohydrate meal in sedentary and physically active subjects.

The study was designed to determine metabolic and hormonal responses to acute modification of body carbohydrate stores by exercise and subsequent meals and to find out whether the responses depend on the training status of subjects. Nine sedentary students and 10 endurance athletes took part in four experimental sessions. During control session, after overnight fast oxygen uptake and CO2 production were measured and blood glucose, free fatty acids (FFA), insulin (I), leptin (L), growth hormone (GH), testosterone (T), catecholamines, ACTH and cortisol were determined. The remaining sessions were preceded by 1.5 h exercise at 70% HRmax in the evening followed by 12-16 hrs fast till morning when subjects ate either high-carbohydrate (H-CHO) or low-carbohydrate (L-CHO) meal or fasted. Respiratory gases and blood samples were collected before and 2 hours after meal. In glycogen depleted subjects respiratory quotient (RQ), I, norepinephrine (NE) and L decreased, whilst other variables were unaltered. Changes in I and NE were greater in athletes than in sedentary subjects. After H-CHO RQ, blood glucose, I and NE increased and FFA, GH and T decreased. The latter effect was greater in athletes than in untrained subjects. After L-CHO, RQ was at the fasting level and FFA increased only in sedentary group. In both groups I increased and GH and T decreased. Neither meal affected L concentration. In conclusion, hormonal and metabolic changes observed after depleting carbohydrate stores resemble those occurring during starvation. Composition of the ingested meal affects postprandial metabolism, which additionally depends on the subjects' training status.

Relationships between plasma adrenomedullin concentration and systolic time intervals during static handgrip in patients with heart failure.

Our previous study showed elevation of plasma adrenomedullin (ADM) during static handgrip in patients with heart failure (HF). It is hypothesized that ADM increases with left ventricle dysfunction during handgrip and thus plays a compensatory role. In the present study pre-ejection period (PEP) and left ventricular ejection time (LVET) were used to assess cardiac performance in 24 male HF patients (II/III class NYHA) during two 3-min bouts of handgrip at 30% of maximal voluntary contraction (MVC) performed alternately with each hand without any break between the bouts. Plasma ADM, noradrenaline (NA), adrenaline (A), heart rate (HR), blood pressure (BP) and stroke volume (SV) were determined. During handgrip plasma ADM, NA, A, HR, BP, PEP/LVET increased, PEP was prolonged and LVET shortened. The increases in plasma ADM correlated with changes in: PEP (r = -0.881), LVET (r = 0.713), PEP/LVET (r = -0.769), SV (r = 0.836), diastolic BP (r = 0.700), total peripheral resistance (TPR) (r = 0.718) and noradrenaline (r = 0.756). The study demonstrated that in HF patients changes in plasma ADM during handgrip are related to cardiac performance.

Influence of body carbohydrate store modification on catecholamine and lactate responses to graded exercise in sedentary and physically active subjects.

Aim of this study was to elucidate the influence of carbohydrate store modification on exercise capacity and catecholamine thresholds. Nine sedentary students and 10 endurance athletes volunteered for the study consisting of four sessions in one-week intervals. During control session (C) subjects performed graded exercise till exhaustion with workload increasing by 50 Watts every 3 min after an overnight fast. Blood lactate and catecholamines were determined at rest, after each workload and at exhaustion. In the evening preceding each of the remaining three sessions subjects performed glycogen reducing exercise lasting 1.5 hrs at 70% HRmax. Till next morning they did not eat any meal but drank water. Two hours before exercise subjects were given either a high-carbohydrate (H-CHO) or a low-carbohydrate (L-CHO) meal of approx. 1000 kcal or remained fasted (F). Depletion of carbohydrate stores enhanced contribution of fat-derived energy substrates at submaximal workloads, but did not influence either maximal oxygen consumption, workload and lactate concentration or lactate threshold. Low carbohydrate availability resulted in elevated concentration of catecholamines only in untrained subjects. Ingestion of a meal either high or low in carbohydrates diminished those changes. Catecholamine thresholds were similar in all sessions and higher in athletes' group.

Effect of adrenergic blockade on plasma adrenomedullin concentration during static handgrip in patients with heart failure.

Our previous study showed that static handgrip caused increases in the plasma adrenomedullin (ADM) both in patients with heart failure (HF) and healthy subjects. The present study was designed to determine the role of the sympathetic nervous system in mediating plasma ADM changes during handgrip in patients with HF. Twelve male HF patients (II class NYHA) treated with carvedilol, a non-selective adrenergic blocker (TC) and 12 patients untreated with carvedilol (UC) performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand. At the end of both exercise bouts and in 5 min of the recovery period, plasma ADM and catecholamines were determined. In addition, heart rate, blood pressure and stroke volume (SV) were measured. The baseline plasma ADM, noradrenaline (NA) and adrenaline (A) levels were similar in the two groups of patients, while SV was higher (P<0.05) in TC than in UC. During exercise plasma ADM concentrations were lower (P<0.05) in TC than in UC, but the handgrip-induced increases in plasma ADM did not differ between the groups. Plasma ADM correlated with NA concentrations (r = 0.764) and with SV (r = -0.435) and increases in plasma ADM expressed as percentage of baseline values correlated with those of plasma NA (r = 0.499), diastolic BP (r = 0.550) and total peripheral resistance (r = 0.435). The study suggests that the sympathetic nervous system may be involved in the stimulation of ADM secretion during static exercise either directly or by changes in the haemodynamic response.

Effect of 6-week endurance training on hemodynamic and neurohormonal responses to lower body negative pressure (LBNP) in healthy young men.

Endurance training is considered as a factor impairing orthostatic tolerance although an improvement and lack of effect have been also reported. The mechanisms of the changes and their relation to initial tolerance of orthostasis are not clear. In the present study, effect of moderate running training on hemodynamic and neurohormonal changes during LBNP, a laboratory test simulating orthostasis, was investigated in subjects with high (HT) and low (LT) tolerance of LBNP. Twenty four male, healthy subjects were submitted to graded LBNP (-15, -30 and -50 mmHg) before and after training. During each test heart rate (HR), stroke volume (SV) and blood pressure, plasma catecholamines, ACTH, adrenomedullin, atrial natriuretic peptide, and renin activity were determined. Basing on initial test, 13 subjects who withstood LBNP at -50 mmHg for 10 min were allocated into HT group and 11 subjects who earlier showed presyncopal symptoms to LT group. Training improved LBNP tolerance in six LT subjects. This was associated with attenuated rate of HR increase and SV decline (before training, at -30 mmHg deltaHR was 21 +/- 4 beats/min and deltaSV - -36+/- 8 ml while after training the respective values were 8 +/- 4 beats/min and -11+/- 6 ml). No differences in hemodynamic response were found in HT subjects and those from LT group whose LBNP tolerance was unchanged. In neither group training affected neurohormonal changes except inhibition of plasma ACTH rise in subjects with improvement of LBNP tolerance. It is concluded that some subjects with low orthostatic tolerance may benefit from moderate training due to improvement of cardiac function regulation.

Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.

Effect of prolonged dynamic exercise on plasma adrenomedullin concentration in healthy young men.

The aim of the study was to find out whether prolonged exercise influences plasma adrenomedullin (ADM) concentration and whether it is related to the hormonal, metabolic and cardiovascular changes. Eighteen healthy subjects (age 25+/-1 yrs) were submitted to cycle exercise for 90 min at 70% of maximal oxygen uptake. Heart rate (HR) and blood pressure (BP) were measured continously. Before, at 30(th) min, and at the end of exercise venous blood samples were taken for [ADM], noradrenaline [NA], adrenaline [A], atrial natriuretic peptide [ANP], plasma renin activity PRA, interleukin-6 [IL-6] and lactate [LA] determination. Significant increases in plasma ADM and IL-6 were found at 90(th) min whereas other hormones were elevated already at 30(th) min of exercise. Positive correlations were ascertained between [ADM] and [NA] (r=0.47), [ANP] (r=0.35) or [IL-6] (r=0.35) and between exercise-induced increases in [ADM] and [NA] (r=0.38). PRA correlated positively with [NA] and [ANP]. Negative correlation was found between plasma [ADM] and diastolic BP. The present data suggest that increase in sympathetic nervous activity and cytokine induction during prolonged exercise may be involved in plasma ADM release and that increase in ADM and ANP secretion may be a compensatory mechanism against further elevation of blood pressure.

Cardiovascular and neurohormonal responses to lower body negative pressure (LBNP): effect of training and 3 day bed rest.

Both intensive training and bed confinement impair orthostatic tolerance, however, moderate training may exert beneficial effect on cardiovascular adjustment to gravitational stimuli. It was hypothesized that moderate training attenuates effects of bed rest. To test this assumption 24 healthy male volunteers aged 20.8+/-0.9 yrs were subjected to 6 degrees head down bed rest (HDBR) for 3 days before and after 6 weeks of moderate endurance training. Before and after HDBR graded LBNP tests (-15, -30, -50 mmHg) were performed. During these tests heart rate (HR), stroke volume (SV), blood pressure (BP), plasma catecholamines, ACTH, adrenomedullin, atrial natriuretic peptide, plasma renin activity (PRA) and hematocrit were determined. HDBR did not systematically influence LBNP tolerance up to -50 mmHg, but it enhanced rates of reduction of SV, cardiac output and systolic BP and increased elevations of HR and PRA. Training did not alter significantly effects of HDBR on LBNP-induced changes in HR, SV, CO and TPR but it attenuated decrease in systolic BP and diminished increases in plasma noradrenaline and PRA. In conclusion, training has negligible effect on the HDBR-induced changes in central hemodynamics during LBNP but may increase vascular sensitivity to some vasoconstricting factors.

Hemodynamic and neuroendocrine predictors of lower body negative pressure (LBNP) intolerance in healthy young men.

Exposure to LBNP results in body fluid shift to lower extremities similarly as under influence of orthostatic stress. In susceptible persons it leads to syncope. For better understanding why certain individuals are more susceptible to orthostatic challenges it seemed necessary to collect more data on hemodynamic and neuroendocrine adjustments occurring before onset of presyncopal symptoms Accordingly, in this study heart rate (HR), blood pressure (BP), stroke volume (SV), cardiac output (CO), hematocrit, plasma catecholamines, adrenomedullin, ACTH and plasma renin activity (PRA) were measured in 24 healthy men during graded LBNP (-15, -30 and -50 mmHg). Thirteen subjects completed the test (HT group) whereas 11 had presyncope signs or symptoms at -30 mmHg or at the beginning of -50 mmHg (LT group). Comparison of these groups showed that LT subjects had lower baseline total peripheral resistance and higher plasma adrenomedullin. During LBNP plasma catecholamine and PRA increases were even greater in LT than in HT group while plasma adrenomedullin elevations were similar in both groups. Plasma ACTH increased only in LT group following presyncope symptoms. Low tolerant group showed more rapid decline of SV and CO than HT subjects from the beginning of LBNP. It is suggested that measurements of SV at the level of LBNP which did not evoke any adverse symptoms may be of predictive value for lower orthostatic tolerance.

Early effects of short-term endurance training on hormonal responses to graded exercise.

Twelve male, sedentary volunteers (22.0 +/-) were submitted to three weeks of a bicycle ergometer training, consisting of 45 min exercise (at 70% VO2max), 4 times in the first week and 3 times in the next 2 weeks. They performed four incremental exercise tests with the power output increased by 50 W every 3 min until volitional exhaustion: two before training (C1 and C2), and after one (T1) and three (T3) weeks of training. Before and after each load the plasma noradrenaline (NA), adrenaline (A) and blood lactate (LA) concentrations were determined in venous blood samples as well as plasma growth hormone (HGH) and cortisol concentrations before and at the end of exercise. A decrease in NA concentration was found already after 1 week of training at power output of 100 W (p<0.01) and 200 W (p<0.05). Similar decline was maintained after 3 weeks of training. No significant training-induced differences in plasma A concentration were found, however, the thresholds for both catecholamines were significantly shifted towards higher values after 3 weeks of training. One week of training caused a decrease in the pre-exercise (p<0.01), as well as post-exercise (p<0.05) plasma cortisol and HGH concentrations. It was concluded that endurance training induced a decrease in HGH, cortisol and NA concentration already after one week of training. A decline of pre-exercise plasma HGH and cortisol levels with time of experiment may, in part, indicate familiarization to exercise protocol.

Exercise training and 3-day head down bed rest deconditioning: exercise thermoregulation.

UNLABELLED: Bed rest (BR) deconditioning causes excessive increase of exercise core body tempera-ture, while aerobic training improves exercise thermoregulation. The study was designed to determine whether 3 days of 6 degrees head-down bed rest (HDBR) affects body temperature and sweating dynamics during exercise and, if so, whether endurance training before HDBR modifies these responses. Twelve healthy men (20.7+/-0.9 yrs, VO2max: 46+/-4 ml x kg(-1) x min(-1) ) underwent HDBR twice: before and after 6 weeks of endurance training. Before and after HDBR, the subjects performed 45 min sitting cycle exercise at the same workload equal to 60% of VO2max determined before training. During exercise the VO2, HR, tympanic (Ttymp) and skin (Tsk) temperatures were recorded; sweating dynamics was assayed from a ventilated capsule on chest. Training increased VO2max by 12.1% (p<0.001). Resting Ttymp increased only after first HDBR (by 0.22 +/- 0.08 degrees C, p<0.05), while exercise equilibrium levels of Ttymp were increased (p<0.05) by 0.21 +/- 0.07 and 0.26 +/- 0.08 degrees C after first and second HDBR, respectively. Exercise mean Tsk tended to be lower after both HDBR periods. Total sweat loss and time-course of sweating responses were similar in all exercise tests. The sweating threshold related to Ttymp was elevated (p<0.05) only after first HDBR. IN CONCLUSION: six-week training regimen prevents HDBR-induced elevation of core temperature (Ttymp) at rest but not during ex-ercise. The post-HDBR increases of Ttymp without changes in sweating rate and the tendency for lower Tsk suggest an early (<3d) influence of BR on skin blood flow.

Heterogeneity of extraparenchymal primitive neuroectodermal tumors within the craniospinal axis.

Four cases of primitive neuroectodermal tumors (PNETs) with unusual localization (three intraspinal extramedullary and one pontocerebellar) are reviewed. Histologically, they were small round blue cell tumors with diverse patterns. Immunohistochemically, all tumors were positive for at least two neuronal markers, two cases were Mic-2 positive and one showed glial differentiation. The paraffin-embedded tumor specimens were examined by interphase FISH using dual-color probes specific for EWS, HER-2 and BCR loci. Molecular cytogenetic study revealed the presence of EWS rearrangement in two cases and the presence of i(17q) in one tumor. Three tumors exhibited 22 disomy and one was 22 polyploid. Extraparenchymal PNETs within craniospinal axis are heterogeneous from the clinical, histological, immunohistochemical and molecular point of view. These PNETs can be of a central or peripheral type. Multidisciplinary approach is of a basic importance in differential diagnosis of such cases.

Catecholamine responses to environmental stressors in trained and untrained men after 3-day bed rest.

INTRODUCTION: The effect of decreased physical activity with reduced gravitational stress on activity, sensitivity, and reactivity of the sympathetic nervous system (SNS) is not fully recognized. We hypothesized that the effect is most pronounced in physically active subjects. Thus, basal plasma norepinephrine [NE] and epinephrine [E], and catecholamine responses to physiological stimuli were determined after 3 d of horizontal bed rest (BR) in subjects differing in level and kind of habitual activity. METHODS: Before and after BR, 11 untrained students, 8 endurance athletes, and 10 power/strength athletes were submitted to oral glucose tolerance test (OGTT) and orthostatic stand test (OST). Another 32 men (12 untrained, 10 endurance athletes, and 10 power/strength athletes) underwent cold pressor test (CPT) and graded exercise test (GET) performed until volitional exhaustion. RESULTS: After BR, basal [NE] was decreased only in athletes (p < 0.01). Increases in both catecholamines during OGTT were diminished (p < 0.05), particularly in endurance athletes. Plasma [NE] response to standing was not affected by BR in individual groups, but it was diminished in the whole group (p < 0.05). Bed rest did not affect the increases in catecholamines induced by CPT and GET. Heart rate response to OST, and BP responses to OST, CPT, and glucose ingestion were enhanced. CONCLUSIONS: Basal sympathetic activity is diminished after 3 d of BR in physically active men. Although catecholamine responses to glucose load and standing were reduced, the general reactivity and sensitivity of SNS were not attenuated since catecholamine responses to the most (exercise) and least (CPT) powerful stimuli were unchanged.