Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Sequencing in Metastatic Renal Cell Carcinoma

The influx of multiple novel therapeutic options in the mRCC field has brought a challenge for treatment sequencing in this disease. In the past few years, cabozantinib, nivolumab and the combination of lenvatinib and everolimus have been approved in the second-line setting. As there is no direct comparison between these agents and the studies have failed to show improved benefit among a biomarker-selected patient population, appropriate patient selection based on clinical factors for individualized therapy is critical. Herein we provide a comprehensive overview of current data from each agent through the discussion of disease biology, clinical trials, potential biomarkers and distilling future perspectives in the field.
SOCIAL COGNITION AND NEUROCOGNITIVE DEFICITS IN SCHIZOPHRENIA

While research equivocally supports a relationship between social cognition and neurocognition, it is less clear whether social cognition is related to general cognitive functioning or whether specific aspects of social cognition are linked with specific forms of neurocognition. Thus, this study sought to investigate the relationships between various domains of neurocognition and two forms of social cognition, social cue recognition and social problem solving, for 40 people with schizophrenia spectrum disorders. Step-wise multiple regressions found that performance on neurocognitive tests was able to predict 47% and 38% of the variance on measures of the ability to recognize actual and suggested social cues, respectively, and 13% of participants’ ability to problem solve in ambiguous social situations. Once estimated intelligence and hospitalization history were controlled, however, neurocognition no longer significantly predicted social problem solving. Executive functioning was uniquely related to each type of social cue recognition, while memory predicted only the recognition of concrete social cues.
Characterization of porcine UL16‐binding protein 1 endothelial cell surface expression

Abstract: Background: Natural killer (NK) cells participate in the immune response against solid organ allo‐ and xenografts and are tightly regulated through signals mediated by inhibiting and activating receptors expressed on their cell surface. Human NK cytotoxicity against porcine endothelial cells (pEC) is mediated by the interaction of the activating human NK receptor hNKG2D and its corresponding ligand on pEC, porcine UL‐16 binding protein 1 (pULBP1). The aim of the present study was to characterize the regulation of pULBP1 cell‐surface expression on primary porcine aortic endothelial cells (PAEC).
RELEASE OF ENDOTHELIN IN RELATION TO TUMOR NECROSIS FACTOR-α IN PORCINE PSEUDOMONAS AERUGINOSA-INDUCED SEPTIC SHOCK

Septic shock is characterized by surges of tumor necrosis factor-α (TNF-α) along with myocardial dysfunction and systemic hypotension. TNF-α promotes the release of immunoreactive endothelin (ET). Because TNF-α is elevated in septic shock, we hypothesized that elevated levels of endothelin can contribute to cardiac dysfunction and hypotension. We infused live Pseudomonas aeruginosa into anesthetized, hemodynamically monitored young swine and measured ET and TNF-α. Septic swine developed systemic arterial hypotension and had significantly elevated TNF-α (4.15 ± .41 U/ml at 1 h versus .40 ± .13 U/ml at time zero) compared to control animals. ET levels were significantly elevated at 4 h (52.38 ± 12.88 pg/ml vs. 10.45 ± 1.82 pg/ml at time zero) and correlated negatively with the decline in cardiac output. We then passively immunized swine using anti TNF-α prior to the induction of sepsis to examine if TNF played a central role in the release ET. The anti TNF-α effectively removed circulating TNF-α bioactivity in septic animals. Anti-TNF-α-treated animals did not develop significant systemic arterial hypotension and had significant attenuation in endothelin (19.01 ± 4.18 pg/ml at 4 h compared to 52.38 ± 12.88 pg/ml in septic animals at 4 h) which correlated with preservation of cardiac output. TNF-α may cause cardiac dysfunction in sepsis syndrome through increased release of ET.
Automatic Traffic Density Estimation and Vehicle Classification for Traffic Surveillance Systems Using Neural Networks

It is important to know the road traffic density real time especially in mega cities for signal control and effective traffic management. In recent years, video monitoring and surveillance systems have been widely used in traffic management. Hence, traffic density estimation and vehicle classification can be achieved using video monitoring systems. In most vehicle detection methods in the literature, only the detection of vehicles in frames of the given video is emphesized. However, further analysis is needed in order to obtain the useful information for traffic management such as real time traffic density and number of vehicle types passing these roads. This paper presents vehicle classification and traffic density calculation methods using neural networks. The paper also reports results from real traffic videos obtained from Istanbul Traffic Management Company (ISBAK).
High-Dimension Multilabel Problems: Convex or Nonconvex Relaxation?

This paper is concerned with the problem of relaxing non convex functionals, used in image processing, into convex problems. We review most of the recently introduced relaxation methods, and we propose a new convex one based on a probabilistic approach, which has the advantages of being intuitive, flexible and involving an algorithm without inner loops. We investigate in detail the connections between the solutions of the relaxed functionals with a minimizer of the original one. Such connection is demonstrated only for non convex relaxation which turns out to be quite robust to initialization. As a case of study, we illustrate our theoretical analysis with numerical experiments, namely for the optical flow problem.
Thermal equation of state and thermodynamic properties of iron carbide Fe3C to 31 GPa and 1473 K

Resent experimental and theoretical studies suggested preferential stability of Fe3C over Fe7C3 at the condition of the Earth's inner core. Previous studies showed that Fe3C remains in an orthorhombic structure with the space group Pnma to 250 GPa, but it undergoes ferromagnetic (FM) to paramagnetic (PM) and PM to nonmagnetic (NM) phase transitions at 6–8 and 55–60 GPa, respectively. These transitions cause uncertainties in the calculation of the thermoelastic and thermodynamic parameters of Fe3C at core conditions. In this work we determined P‐V‐T equation of state of Fe3C using the multianvil technique and synchrotron radiation at pressures up to 31 GPa and temperatures up to 1473 K. A fit of our P‐V‐T data to a Mie‐Gruneisen‐Debye equation of state produce the following thermoelastic parameters for the PM‐phase of Fe3C: V0 = 154.6 (1) Å3, KT0 = 192 (3) GPa, KT′ = 4.5 (1), γ0 = 2.09 (4), θ0 = 490 (120) К, and q = −0.1 (3). Optimization of the P‐V‐T data for the PM phase along with existing reference data for thermal expansion and heat capacity using a Kunc‐Einstein equation of state yielded the following parameters: V0 = 2.327 cm3/mol (154.56 Å3), KT0 = 190.8 GPa, KT′ = 4.68, ΘE10 = 305 K (which corresponds to θ0 = 407 K), γ0 = 2.10, e0 = 9.2 × 10−5 K−1, m = 4.3, and g = 0.66 with fixed parameters mE1 = 3n = 12, γ∞ = 0, β = 0.3, and a0 = 0. This formulation allows for calculations of any thermodynamic functions of Fe3C versus T and V or versus T and P. Assuming carbon as the sole light element in the inner core, extrapolation of our equation of state of the NM phase of Fe3C suggests that 3.3 ± 0.9 wt % С at 5000 К and 2.3 ± 0.8 wt % С at 7000 К matches the density at the inner core boundary.
Morphologic Reproducibility, Genotyping, and Immunohistochemical Profiling Do Not Support a Category of Seromucinous Carcinoma of the Ovary

The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The morphologic diagnosis of seromucinous carcinomas is not very reliable and it does not exhibit a distinct immunophenotype or genotype. The molecular features overlap mostly with endometrioid and low-grade serous carcinomas. Our data suggest the category of seromucinous carcinoma be discontinued as ancillary molecular tests can assign cases to one of the major histotypes.
An Input-output Analysis of Sources of Growth and Key Sectors in Malaysia

The paper examines the sources of growth and key sectors of Malaysia’s economy over 1978-2000 using a decomposition method and Rasmussen degree of dispersion within the input-output (IO) framework. The model uses three comparable IO tables for 1978, 1991 and 2000 as the main data sources and accounts for output changes from a demand side perspective. The chosen structural decomposition analysis (SDA) based on the comparison between two IO tables, allows us to decompose each sector’s and industry’s output growth. It decomposes output growth of each sector to domestic demand expansion, export demand expansion, import substitution of final goods, import substitution of intermediate goods, and changes in IO coefficients. The analysis by sub periods, 1978-1991 and 1991-2000 show that there was a switch in the role of domestic-demand and export-demand expansion. The constituent factors that contribute positively to change in the period, 1978-1991 are mostly domestic demand expansion (63.35%) and export demand expansion (33.33%). However in the second sub period, 1991-2000, export demand expansion increased by 12.43% and domestic demand expansion decreased to 48.11%. Taking the whole 1978-2000, domestic demand expansion appears to have been the major source of output growth, contributing about 82%, followed by export demand expansion 62%. Combining the source of growth and key sector through backward linkages, the study revealed that most of the sectors induced its supplying production strongly for domestic market.
Studies of Fluorocardiography in Normal Subjects

Summary A study of 15 normal subjects has been performed by using fluorocardiog-raphy, a method which permits recording on a continuous film of the pulsations of various cardiovascular structures revealed by the x-ray. (a) The tracing of the ascending aorta presents a typical pattern which partly is due to transmission of intraventricular pressure and partly to motions of the aortic root connected with ventricular systole and diastole. (b) It is possible to record in certain cases a tracing of the pulmonary veins. Its most typical feature is a positive wave during presystole, (c) The velocity of the pulse wave in the lesser circulation is much lower than in the greater circulation. It is more rapid in the smaller branches than in the stems of the pulmonary artery. Average figures are given, (d) The tracing of the pulmonary parenchyma is the equivalent of a pie thy sinogram. While the rise and the ascending branch of the wave are of arterial pulmonary origin, the peak and the descending branch of the wave are probably of venous pulmonary origin.
Periorbital Hyperpigmentation in Asians: An Epidemiologic Study and a Proposed Classification

BACKGROUND Periorbital hyperpigmentation (POH) presents with a dark area surrounding the eyelids. It is an ill‐defined condition, and the pathogenesis can be multifactorial. OBJECTIVE This epidemiologic study was conducted to assess the prevalence of periorbital hyperpigmentation in Singapore in an attempt to propose a classification. MATERIALS AND METHODS One thousand consecutive patients attending the general dermatology clinic at the National Skin Center were enrolled in the study to assess for POH, of whom 200 with POH were examined and investigated to define the cause of POH. The possible causes were determined according to a detailed history, clinical examination, and assessment by three dermatologists. The extent of the POH was measured using a mexameter. RESULTS The commonest form of POH was the vascular type (41.8%), followed by constitutional (38.6%), postinflammatory hyperpigmentation (12%), and shadow effects (11.4%). The vascular type was seen predominantly in Chinese, whereas as the constitutional type was most common in Indians and Malays. CONCLUSION The vascular form of POH was the predominant type. We propose a comprehensive classification for POH that we hope will influence the choice of treatment modalities used in managing POH in the future. Unilever R&D Trumbul, USA provided funding for this study.
Electrohydrodynamic flow of dielectric liquid around a wire electrode - effect of truncation of onsager function

Electrohydrodynamic flow of a dielectric liquid around a wire electrode sandwiched between two parallel flat-plate electrodes is studied both numerically and experimentally. The Poisson-Nernst-Planck equations for the ion transport and the Navier-Stokes equations for the fluid flow are solved numerically by using a commercial code. Charge generation in a dielectric liquid (dodecane + 0.5% wt Span 80) due to Onsager effect is considered in the ion transport equations. Numerical results well predict the experimental ones both qualitatively and quantitatively. At high electric field the numerical approach slightly over-predicts the flow velocity measured from the experiment, but the level of discrepancy can be further lowered by using a truncated series for the Onsager function.
DOPA-RESPONSIVE DYSTONIC CAMPTOCORMIA

We read Dr. van Gerpen’s article in which he reports a patient with camptocormia remarkably responsive to levodopa treatment.1 The authors report that having the patient walk backwards improved the position of the patient’s spine, which was equated to a sensory trick. It was concluded that camptocormia was due to dystonia because of the presence of diurnal fluctuation and …
Pharmacokinetics and tissue penetration of Ro 23-6240, a new trifluoroquinolone

A 400-mg dose of the trifluorinated quinolone Ro 23-6240 was administered orally to each of six healthy male volunteers, after which the concentrations of this agent in serum and cantharidin-induced inflammatory fluid were measured. Absorption was rapid, with a mean peak level in serum of 6.1 micrograms/ml, which was attained 0.71 h after administration. The elimination half-life in serum was 11.95 h. The agent penetrated the inflammatory fluid rapidly; the percent penetration was 89.7%. Urinary recovery of Ro 23-6240 was 58.6% by 72 h.
Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II

Mutations in USH2A gene have been shown to be responsible for Usher syndrome type II, an autosomal recessive disorder characterised by hearing loss and retinitis pigmentosa. USH2A was firstly described as consisting of 21 exons, but 52 novel exons at the 3’ end of the gene were recently identified. In this report, a mutation analysis of the new 52 exons of USH2A gene was carried out in 32 unrelated patients in which both disease-causing mutations could not be found after the screening of the first 21 exons of the USH2A gene. On analysing the new 52 exons, fourteen novel mutations were identified in 14 out of the 32 cases studied, including 7 missense, 5 frameshift, 1 duplication and a putative splice-site mutation.
Hearing and Verbal‐Cognitive Abilities in High‐Risk Preterm Infants Prone to Otitis Media with Effusion

Preterm infants with a history of perinatal complications are at risk for language learning difficulties, and are more likely than full-term infants to show recurrent otitis media. The present study looks at the association between these risk outcomes in the preschool period. Twenty-three otitis-prone preterm children (referred to as cases) were compared with 20 non-otitis-prone children with similar perinatal and demographic characteristics (controls). Hearing thresholds were depressed for the cases in conjunction with abnormal tympanograms, and hearing was significantly poorer than for controls. Some language and verbal cognitive abilities were significantly poorer for the cases. The findings suggest the importance of medical intervention, audiometric assessment, and speech and language follow-up for high-risk premature infants prone to otitis media with effusion.
Physiological Activation in Patients With Sleep State Misperception

Objective Sleep State Misperception insomnia has been commonly viewed as a perceptual or psychological problem. It was hypothesized that Sleep State Misperception insomnia, like psychophysiological insomnia, could be associated with increased physiological activation, here indexed by whole body metabolic rate. Method Groups of nine patients with Sleep State Misperception insomnia and age-, sex-, and weight-matched normal sleepers were evaluated on sleep, performance, mood, personality, and metabolic measures over a 36-hour sleep laboratory stay. Results Sleep State Misperception insomniacs had a subjective history of poor sleep and perceived their laboratory sleep as poor but had electroencephalogram (EEG) parameters that did not differ statistically from matched normal controls. Sleep State Misperception insomniacs had abnormal MMPI values and were subjectively more confused, tense, depressed, and angry than matched normals. Sleep State Misperception insomniacs also had a significantly increased 24-hour metabolic rate, compared with matched normals. Conclusions The overall increase in whole body oxygen use was less than that seen in psychophysiological insomniacs but was consistent with the view that Sleep State Misperception insomnia may be a mild version or a precursor to psychophysiological insomnia.
GENETIC AND ENVIRONMENTAL VARIATION IN ANTIBODY AND T‐CELL MEDIATED RESPONSES IN THE GREAT TIT

Abstract Host parasite coevolution assumes pathogen specific genetic variation in host immune defense. Also, if immune function plays a role in the evolution of life history, allocation to immune function should be heritable. We conducted a cross‐fostering experiment to test the relative importance of genetic and environmental sources of variation in T‐cell mediated inflammatory response and antigen specific antibody responses in the great tits Parus major. Cell mediated response was measured during the nestling period and antibody response against two novel antigens was measured in two‐month‐old juveniles raised in a laboratory. We found no effect of nest of origin, but a strong effect of rearing environment on cell mediated response. In contrast, we found a large effect of nest of origin on antibody response to both, diphtheria and tetanus antigens suggesting genetic variation. In a model where responses to both antigens were analyzed simultaneously, we found a significant origin‐by‐antigen interaction, suggesting that genetic variation in antibody responses is specific to particular antigens. Large genetic variation in antibody responses found in this study suggests that host immune defense may evolve and specificity of genetic variation in antibody responses suggests that host defense may be pathogen specific as models of host‐parasite coevolution suggest. Our results also suggest that different immune traits are to some degree independent and outcome of the interactions between immune function and the environment may depend on the particular immune trait measured.
Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder.

OBJECTIVE To determine the relative effects of risperidone and divalproex in pediatric mania. METHODS This is a double-blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age= 10.9 ± 3.3 years; age range= 8-18 years) with mania who were randomly assigned to either risperidone (0.5-2 mg/day, n= 33) or divalproex (60-120 μg/mL, n= 33) for a six-week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale-Revised (CDRS-R). RESULTS Mixed-effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six-week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS-R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group. CONCLUSION Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidone's lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings.
Imaging in dementia with Lewy bodies: a review

This review discusses the role of functional and structural imaging in patients with suspected dementia with Lewy bodies, with particular emphasis on SPECT and PET dopaminergic and cerebral perfusion/metabolic techniques. It is envisaged that this information may be useful to nuclear medicine physicians, radiologists, psychiatrists, neurologists, geriatricians and physicians.