Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic abnormalities of the EGFR pathway in African American Patients with non-small-cell lung cancer.

PURPOSE Previous studies in non-small-cell lung cancer (NSCLC) have demonstrated a wide variation in responsiveness to epidermal growth factor receptor (EGFR) -targeting agents and in genetic aberrancies of the EGFR pathway according to ethnic background, most notably a higher frequency of activating EGFR mutations among East-Asian patients. We investigated the frequency of EGFR pathway aberrancies among African American patients with NSCLC, for whom limited information presently exists. PATIENTS AND METHODS EGFR fluorescent in situ hybridization (FISH) was performed on archived tissues from 53 African American patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21 and KRAS exon 2. Results were compared by multivariate analysis to an historical control cohort of 102 white patients with NSCLC. RESULTS African Americans were significantly less likely to harbor activating mutations of EGFR than white patients (2% v 17%; P = .022). Only one EGFR mutation was identified, a novel S768N substitution. EGFR FISH assay was more frequently positive for African Americans than for white patients (51% v 32%; P = .018). KRAS mutational frequency did not differ between the groups (23% v 21%; P = .409). CONCLUSION African American patients with NSCLC are significantly less likely than white counterparts to harbor activating mutations of EGFR, which suggests that EGFR tyrosine kinase inhibitors (TKIs) are unlikely to yield major remissions in this population. Our findings add to a growing body of evidence that points to genetic heterogeneity of the EGFR pathway in NSCLC among different ethnic groups and that underscores the need for consideration of these differences in the design of future trials of agents that target the EGFR pathway.
A Separation Principle for the Continuous-Time LQ-Problem With Markovian Jump Parameters

In this paper, we devise a separation principle for the finite horizon quadratic optimal control problem of continuous-time Markovian jump linear systems driven by a Wiener process and with partial observations. We assume that the output variable and the jump parameters are available to the controller. It is desired to design a dynamic Markovian jump controller such that the closed loop system minimizes the quadratic functional cost of the system over a finite horizon period of time. As in the case with no jumps, we show that an optimal controller can be obtained from two coupled Riccati differential equations, one associated to the optimal control problem when the state variable is available, and the other one associated to the optimal filtering problem. This is a separation principle for the finite horizon quadratic optimal control problem for continuous-time Markovian jump linear systems. For the case in which the matrices are all time-invariant we analyze the asymptotic behavior of the solution of the derived interconnected Riccati differential equations to the solution of the associated set of coupled algebraic Riccati equations as well as the mean square stabilizing property of this limiting solution. When there is only one mode of operation our results coincide with the traditional ones for the LQG control of continuous-time linear systems.
Kinematic Analysis of Volleyball Attack in the Net Center with Various Types of Take-Off

Abstract The aim of the study was to describe and compare kinematics in two types of execution of attack hit, the goofy approach and regular approach. The research group consisted of players from the Czech Republic’s top league (n = 12, age 28.0 ± 4.3 years, body height 196.6 ± 5.6 cm, body mass 89.7 ± 6.7 kg) divided into two groups according to the individual type of approach in the attack. Analysis of movement was performed by 3D kinematics video analysis, space coordinates were calculated by the DLT (Direct Linear Transformation) method together with interpretation software TEMA Bio 2.3 (Image Systems AB, Sweden). The players started their run-up from a distance of about 4 – 4.5 m from the net with similar maximal vertical velocity (2.91 – 2.96 m⋅s-1). The trajectory of players with goofy approach seemed to be convenient for the rotation of shoulders and hips in the moment of ball contact. Differences between both groups were observed. Players with a goofy approach had a longer flight phase compared to regularly approaching players.
How cognitive neuroscience could be more biological—and what it might learn from clinical neuropsychology

Three widespread assumptions of Cognitive-affective Neuroscience are discussed: first, mental functions are assumed to be localized in circumscribed brain areas which can be exactly determined, at least in principle (localizationism). Second, this assumption is associated with the more general claim that these functions (and dysfunctions, such as in neurological or mental diseases) are somehow generated inside the brain (internalism). Third, these functions are seen to be “biological” in the sense that they can be decomposed and finally explained on the basis of elementary biological causes (i.e., genetic, molecular, neurophysiological etc.), causes that can be identified by experimental methods as the gold standard (isolationism). Clinical neuropsychology is widely assumed to support these tenets. However, by making reference to the ideas of Kurt Goldstein (1878–1965), one of its most important founders, I argue that none of these assumptions is sufficiently supported. From the perspective of a clinical-neuropsychological practitioner, assessing and treating brain damage sequelae reveals a quite different picture of the brain as well as of us “brain carriers”, making the organism (or person) in its specific environment the crucial reference point. This conclusion can be further elaborated: all experimental and clinical research on humans presupposes the notion of a situated, reflecting, and interacting subject, which precedes all kinds of scientific decomposition, however useful. These implications support the core assumptions of the embodiment approach to brain and mind, and, as I argue, Goldstein and his clinical-neuropsychological observations are part of its very origin, for both theoretical and historical reasons.
Sorafenib targets dysregulated Rho kinase expression and portal hypertension in rats with secondary biliary cirrhosis

Background and purpose: Extrahepatic vasodilation and increased intrahepatic vascular resistance represent attractive targets for the medical treatment of portal hypertension in liver cirrhosis. In both dysfunctions, dysregulation of the contraction‐mediating Rho kinase plays an important role as it contributes to altered vasoconstrictor responsiveness. However, the mechanisms of vascular Rho kinase dysregulation in cirrhosis are insufficiently understood. They possibly involve mitogen‐activated protein kinase/extracellular signal‐regulated kinase (ERK)‐dependent mechanisms in extrahepatic vessels. As the multikinase inhibitor sorafenib inhibits ERK, we tested the effect of sorafenib on haemodynamics and dysregulated vascular Rho kinase in rats with secondary biliary cirrhosis.
Evaluation of Coronary Atherosclerosis by Multislice Computed Tomography in Patients With Acute Myocardial Infarction and Without Significant Coronary Artery Stenosis: A Comparative Study With Quantitative Coronary Angiography

Background—It is known that 9% to 31% of women and 4% to 14% of men with acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at angiography. These patients represent a diagnostic and therapeutic challenge. Multislice computed tomography (CT) can noninvasively identify the presence of coronary plaques even in the absence of significant coronary artery stenosis. This study evaluated the role of 64-slice CT, in comparison with coronary angiography, in detecting and characterizing coronary atherosclerosis in patients with acute myocardial infarction without significant coronary artery stenosis. Methods and Results—Thirty consecutive patients with acute myocardial infarction but without significant coronary stenosis at coronary angiography underwent 64-slice CT. All coronary segments were quantitatively analyzed by means of coronary angiography (CA-QCA) and 64-slice CT (CT-QCA). Forty-seven (10.4%) of the 450 coronary segments were not evaluable by CT. The mean proximal reference diameters at CT-QCA and CA-QCA were, respectively, 2.88±0.75 mm and 2.65±0.9 mm; the overall correlation between CT-QCA and CA-QCA for quantification of reference diameter was rs=0.77; P<0.001. The mean percent stenosis was 14.4±8.0% at CT-QCA and 4.0±11.0% at CA-QCA and the correlation was rs=0.11; P=0.03. Overall CT-QCA showed the presence of 50 plaques, of which only 11 were detected by CA-QCA. CT-QCA identified 25 plaques in infarct-related coronary arteries. Positive remodeling was present in 38 of the 50 plaques (76%), with a higher prevalence in the coronary plaques not visualized by CA-QCA (82.1% versus 54.5%). Conclusions—CT-QCA correlates well with CA-QCA in terms of coronary reference diameter analysis, but not stenosis quantification. Multislice CT can detect coronary atherosclerotic plaques in segments of nonstenotic coronary arteries that are underestimated by CA and may have an incremental diagnostic value for the diagnosis of acute myocardial infarction in patients without significant coronary stenosis at CA.
Differences in colonisation of five marine bacteria on two types of glass surfaces

The retention patterns of five taxonomically different marine bacteria after attachment on two types of glass surfaces, as-received and chemically etched, have been investigated. Contact angle measurements, atomic force microscopy (AFM), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), X-ray fluorescence spectroscopy (XRF) and X-ray photoelectron spectrometry (XPS) were employed to investigate the impact of nanometer scale surface roughness on bacterial attachment. Chemical modification of glass surfaces resulted in a ∼1 nm decrease in the average surface roughness (R a) and the root-mean-squared roughness (Rq ) and in a ∼8 nm decrease in the surface height and the peak-to-peak (R max) and the 10-point average roughness (Rz ). The study revealed amplified bacterial attachment on the chemically etched, nano-smoother glass surfaces. This was a consistent response, notwithstanding the taxonomic affiliation of the selected bacteria. Enhanced bacterial attachment was accompanied by elevated levels of secreted extracellular polymeric substances (EPS). An expected correlation between cell surface wettability and the density of the bacterial attachment on both types of glass surfaces was also reported, while no correlation could be established between cell surface charge and the bacterial retention pattern.
Psychosocial mediators of racial differences in nighttime blood pressure dipping among normotensive adults.

Shallow declines in nocturnal compared with diurnal blood pressure (BP dipping) have been associated with cardiovascular disease. In U.S. samples, Blacks demonstrate less BP dipping compared with Whites. In a sample of 60 Black and 60 White normotensive adults we examined stress, social integration (including parental status), social support, and hostility as potential mediators of the association between race and BP dipping. The effect of race on diastolic BP dipping was partially mediated by parental status. The effect of race on heart rate dipping was partially mediated by stressful life events. No psychosocial factors mediated the relation between race and systolic BP dipping. Although psychosocial factors appear to account for some of the observed racial differences in nocturnal blood pressure decline, our data suggest that these differences cannot be attributed entirely to covarying psychosocial effects.
Intersecting Families in the Alternating Group and Direct Product of Symmetric Groups

Let $S_{n}$ denote the symmetric group on $[n]=\{1, \ldots, n\}$. A family $I \subseteq S_{n}$ is intersecting if any two elements of $I$ have at least one common entry. It is known that the only intersecting families of maximal size in $S_{n}$ are the cosets of point stabilizers. We show that, under mild restrictions, analogous results hold for the alternating group and the direct product of symmetric groups.
Phylogenetic species recognition and species concepts in fungi.

The operational species concept, i.e., the one used to recognize species, is contrasted to the theoretical species concept. A phylogenetic approach to recognize fungal species based on concordance of multiple gene genealogies is compared to those based on morphology and reproductive behavior. Examples where Phylogenetic Species Recognition has been applied to fungi are reviewed and concerns regarding Phylogenetic Species Recognition are discussed.
An ethical paradox: the effect of unethical conduct on medical students' values

Objective—To report the ethical development of medical students across four years of education at one medical school. Design and setting—A questionnaire was distributed to all four classes at the Wake Forest University School of Medicine during the Spring of 1996. Participants—Three hundred and three students provided demographic information as well as information concerning their ethical development both as current medical students and future interns. Main measurements—Results were analyzed using cross-tabulations, correlations, and analysis of variance. Results—Results suggested that the observation of and participation in unethical conduct1 may have disparaging effects on medical students' codes of ethics with 35% of the total sample (24% of first years rising to 55% of fourth years) stating that derogatory comments made by residents/attendings, either in the patient's presence or absence, were “sometimes” or “often” appropriate. However, approximately 70% of the sample contended that their personal code of ethics had not changed since beginning medical school and would not change as a resident. Conclusions—Results may represent an internal struggle that detracts from the medical school experience, both as a person and as a doctor. Our goal as educators is to alter the educational environment so that acceptance of such behaviour is not considered part of becoming a physician.
Quantitation of the JAK2V617F Mutation in Microdissected Bone Marrow Trephines: Equal Mutational Load in Myeloid Lineages and Rare Involvement of Lymphoid Cells

The JAK2V617F mutation is an essential oncogenic event in Philadelphia negative chronic myeloproliferative disorders (Ph-cMPD). It is still unclear how a unique tyrosine kinase mutation can give rise to the broad clinical and morphologic spectrum of Ph-cMPD. One possible explanation could be differences in the JAK2V617F gene dosage, or different maturation stages on which myeloid lineages are affected by the mutation. The extent of lymphoid lineage involvement in JAK2V617F-positive cMPD is still controversial. We comparatively studied the zygosity status of microdissected megakaryocytes, nonmegakaryocytic hematopoietic cells, and reactive as well as neoplastic lymphoid nodules from bone marrow trephines of 61 patients with Ph-cMPD. The presence of the mutation and mutant gene dosage were determined by allele-specific polymerase chain reaction and TaqMan analysis, respectively. The mutation was detected in 22/32 (68%) cases of essential thrombocythemia, all cases of polycythemia vera, and 4/8 (50%) idiopathic myelofibrosis. Comparison of whole bone marrow sections and the different myeloid lineages showed similar percentages of the mutated allele. Restriction to a particular lineage or major differences in allele dosage were not observed, except for 2 cases in which megakaryocytes revealed a higher frequency of the mutated allele. A heterozygous JAK2V617F mutation was detected in 3/8 “reactive” lymphoid nodule in patients with Ph-cMPD, whereas all concomitant non-Hodgkin lymphoma of B-cell type were negative. These results demonstrate that different myeloid lineages usually show similar frequencies of the JAK2V617F allele. The occasional detection of JAK2V617F in benign lymphocytes points to involvement of the lympho-myeloid stem cell.
Case study: extreme programming in a university environment

Extreme programming (XP) is a new and controversial software process for small teams. A practical training course at the University of Karlsruhe led to the following observations about the key practices of XP. First, it is unclear how to reap the potential benefits of pair programming, although pair programming produces high-quality code. Second, designing in small increments appears to be problematic but ensures rapid feedback about the code. Third, while automated testing is helpful, writing test cases before coding is a challenge. Last, it is difficult to implement XP without coaching. This paper also provides some guidelines for those starting out with XP.
Melatonin reduces hyperalgesia associated with inflammation

Abstract: The perception of pain is altered by inflammatory processes. Anti‐inflammatory drugs block this by raising the pain threshold and by reducing the inflammatory process. Melatonin is claimed to have anti‐inflammatory activity in animal models of acute and chronic inflammation. However, little is known whether melatonin can reverse the hyperalgesia that is secondary to the inflammation. This study assessed the effect of melatonin on in a well‐established model of hyperalgesia associated with inflammation in rats. Peroxynitrite, as generated by the interaction between superoxide anion radical exogenously supplied (O2˙−) and endogenous nitric oxide (NO), led to the development of hyperalgesia. This subplantar injection of O2˙− into the right hindpaw evoked potent thermal hyperalgesia measured by changes in withdrawal latency. Melatonin (25–100 mg/kg, given ip 30 min prior to O2˙−) dose dependently attenuated the hyperalgesic responses to O2˙−. Moreover, melatonin (100 mg/kg) significantly improved tissue damage and inflammation, blocked protein nitration affecting cyclooxygenase‐2 and inducible nitric oxide synthase expression in paw tissue. To investigate the antinociceptive activity of melatonin and characterize the underlying mechanisms involved in this action, mitogen‐activated protein kinase and NF‐κB pathways were explored. Moreover, antihyperalgesic effect of melatonin derived partly from the inhibition of superoxide‐driven PARP activation. These results suggest that melatonin has ameliorative potential in attenuating the hyperalgesia associated with inflammation.
Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis.

OBJECTIVE Although early initiation of disease-modifying antirheumatic drugs (DMARDs) is effective in controlling short-term joint damage in individuals with rheumatoid arthritis (RA), the long-term benefit in disease progression is still controversial. We examined the long-term benefit of early DMARD initiation on radiographic progression in early RA. METHODS We identified published and unpublished clinical trials and observational studies from 1966 to September 2004 examining the association between delay to treatment initiation and progressive radiographic joint damage. We included studies of persons with RA disease duration <2 years and DMARD therapy of similar efficacy during followup. The differences in annual rates of radiographic progression between early and delayed therapy were pooled as standardized mean differences (SMDs). RESULTS A total of 12 studies met the inclusion criteria. The pooled estimate of effects from these studies demonstrated a significant reduction of radiographic progression in patients treated early (-0.19 SMD, 95% confidence interval [95% CI] -0.34, -0.04), which corresponded to a -33% reduction (95% CI -50, -16) in long-term progression rates compared with patients treated later. Patients with more aggressive disease seemed to benefit most from early DMARD initiation (P = 0.04). CONCLUSION These results support the existence of a critical period to initiate antirheumatic therapy, a therapeutic window of opportunity early in the course of RA associated with sustained benefit in radiographic progression for up to 5 years. Prompt initiation of antirheumatic therapy in persons with RA may alter the long-term course of the disease.
A bias-compensated affine projection algorithm for noisy input data

This paper proposes a bias-compensated affine projection algorithm (BC-APA) to eliminate bias due to noisy input data and to reduce the performance degradation due to highly correlated input data. A new affine projection algorithm (new APA) using innovative input data is presented for highly correlated input data. We analyze the bias in this innovative new APA under noisy input data and remove it. To remove the bias, an estimation method for the input noise variance is presented and explained. In simulations, the BC-APA provided both fast convergence rate and small mean square deviation. Based on improved precision to estimate a finite impulse response of an unknown system, the BC-APA can be applied extensively in adaptive signal processing areas.
The effects of progressive resistance training on daily physical activity in young people with cerebral palsy: a randomised controlled trial

Abstract Purpose: To examine if individualised resistance training increases the daily physical activity of adolescents and young adults with bilateral spastic cerebral palsy (CP). Method: Young people with bilateral spastic CP were randomly assigned to intervention or to usual care. The intervention group completed an individualised lower limb progressive resistance training programme twice a week for 12 weeks in community gymnasiums. The primary outcome was daily physical activity (number of steps, and time sitting and lying). Secondary outcomes included muscle strength measured with a one-repetition maximum (1RM) leg press and reverse leg press. Outcomes were measured at baseline, 12 weeks and 24 weeks. Results: From the 36 participants with complete data at 12 weeks, there were no between-group differences for any measure of daily physical activity. There was a likely increase in leg press strength in favour of the intervention group (mean difference 11.8 kg; 95% CI −1.4 to 25.0). No significant adverse events occurred during training. Conclusions: A short-term resistance training programme that may increase leg muscle strength was not effective in increasing daily physical activity. Other strategies are needed to address the low-daily physical activity levels of young people with bilateral spastic CP. Implications for Rehabilitation Progressive resistance training may increase muscle strength but does not lead to increases in daily physical activity of young people with bilateral spastic cerebral palsy (CP) and mild to moderate walking disabilities. Other strategies apart from or in addition to resistance training are needed to address the low daily physical activity levels of young people with bilateral spastic CP and mild to moderate walking disabilities.
Markov chain fingerprinting to classify encrypted traffic

In this paper, we propose stochastic fingerprints for application traffic flows conveyed in Secure Socket Layer/Transport Layer Security (SSL/TLS) sessions. The fingerprints are based on first-order homogeneous Markov chains for which we identify the parameters from observed training application traces. As the fingerprint parameters of chosen applications considerably differ, the method results in a very good accuracy of application discrimination and provides a possibility of detecting abnormal SSL/TLS sessions. Our analysis of the results reveals that obtaining application discrimination mainly comes from incorrect implementation practice, the misuse of the SSL/TLS protocol, various server configurations, and the application nature.