Miracle-dz/UniFAR-FTUs huggingface dataset:
K252a and CEP1347 Are Neuroprotective Compounds That Inhibit Mixed-lineage Kinase-3 and Induce Activation of Akt and ERK*

K252a is best known as a Trk inhibitor, but is also a neuroprotective compound. CEP1347, a K252a derivative, retains neuroprotective properties, but does not inhibit TrkA. CEP1347 has recently been shown to directly inhibit MAPKKKs, including MLK3, but the effect of K252a on MAPKKKs remains unknown. K252a and CEP1347 not only prevent death, but also facilitate neurite outgrowth and maintenance, somal hypertrophy, and neurotransmitter synthesis. The biochemical basis for these trophic effects remains unknown. We have compared the effects of CEP1347 and K252a on MLK and JNK signaling and on neurotrophic pathways that support survival and growth. Our data show that K252a is a potent inhibitor of MLK3 activity in vivo and in vitro (IC50 ∼ 5 nm). However, we also found that K252a and CEP1347 activate Akt and ERK and show that blockade of phosphatidylinositol 3-kinase or MEK activity ablates the effect of K252a and CEP1347 on cell survival. Activation of Akt and ERK occurs through an MLK-independent pathway that may involve c-Src. Together, these data show that the neuroprotective and neurotrophic effects of K252a and CEP1347 involve activation of several neurotrophic signaling pathways.
Establishing and expanding the indications for proton and particle therapy

1 Department of Medical Physics, Aarhus University/Aarhus University Hospital, Aarhus, Denmark, 2 Department of Physics and Technology, University of Bergen, Bergen, Norway, 3 Scripps Proton Radiotherapy Center, San Diego, California, USA, 4 Procure Proton Therapy Centers, New York, New York, USA, 5 Proton Therapy Center, Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, and 6 Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden
QUALITY AND STORAGE STABILITY OF FISH CAKE FROM COMMON CARP ( CYPRINUS CARPIO ) DURING REFRIGERATED STORAGE

Fish cakes prepared from Common carp (Cyprinus carpio) were assessed for proximate, chemical, microbiological and sensory quality changes for a period of 15 days at refrigerated temperature of 4 (±1) °C. The changes in proximate analysis of fish cakes were found to be significant at P <0.01. The values of peroxide value, free fatty acid, Thiobarbutric acid and total volatile base nitrogen at the end of storage increased significantly at P <0.01 were determined as 7.86 (±0.04) meqO2/kg of fat, 0.75 (±0.03)% of oleic acid, 1.42 (±0.02) mg MA/kg of sample and 6.19 (±0.02) mg/ 100 g of sample respectively. Total plate count and psychrophilic bacterial counts increased significantly (P <0.01) during refrigerated storage. Staphylococcus aureus, Faecal streptococci, Escherichia coli, Salmonella, Vibrio, yeast and moulds were found absent. The color changes in fish cake were observed during the entire storage period. According to sensory scores, the fish cakes have a shelf life of 12 days. A negative correlation was observed between storage period and overall acceptability scores.
Increased cortical thickness in a frontoparietal network in social anxiety disorder

Social anxiety disorder (SAD) is the second leading anxiety disorder. On the functional neurobiological level, specific brain regions involved in the processing of anxiety‐laden stimuli and in emotion regulation have been shown to be hyperactive and hyper‐responsive in SAD such as amygdala, insula and orbito‐ and prefrontal cortex. On the level of brain structure, prior studies on anatomical differences in SAD resulted in mixed and partially contradictory findings. Based on previous functional and anatomical models of SAD, this study examined cortical thickness in structural magnetic resonance imaging data of 46 patients with SAD without comorbidities (except for depressed episode in one patient) compared with 46 matched healthy controls in a region of interest‐analysis and in whole‐brain. In a theory‐driven ROI‐analysis, cortical thickness was increased in SAD in left insula, right anterior cingulate and right temporal pole. Furthermore, the whole‐brain analysis revealed increased thickness in right dorsolateral prefrontal and right parietal cortex. This study detected no regions of decreased cortical thickness or brain volume in SAD. From the perspective of brain networks, these findings are in line with prior functional differences in salience networks and frontoparietal networks associated with executive‐controlling and attentional functions. Hum Brain Mapp 35:2966–2977, 2014. © 2013 Wiley Periodicals, Inc.
Odor discrimination by G protein‐coupled olfactory receptors

The vertebrate olfactory system possesses a remarkable capacity to recognize and discriminate a variety of odorants by sending the coding information from peripheral olfactory sensory neurons in the olfactory epithelium to the olfactory bulb of the brain. The recognition of odorants appear to be mediated by a G protein‐coupled receptor superfamily that consists of ∼1% of total genes in vertebrates. Since the first discovery of the olfactory receptor gene superfamily in the rat, similar chemosensory receptors have been found in various species across different phyla. The functions of these receptors, however, had been uncharacterized until the recently successful functional expression and ligand screening of some olfactory receptors in various cell expression systems. The functional cloning of odorant receptors from single olfactory neurons allowed for the identification of multiple receptors that recognized a particular odorant of interest. Reconstitution of the odorant responses demonstrated that odorant receptors recognized various structurally‐related odorant molecules with a specific molecular receptive range, and that odor discrimination is established based on a combinatorial receptor code model in which the identities of different odorants are encoded by a combination of odorant receptors. The receptor code for an odorant changes at different odorant concentrations, consistent with our experience that perceived quality of an odorant changes at different concentrations. The molecular bases of odor discrimination at the level of olfactory receptors appear to correlate well with the receptive field in the olfactory bulb where the input signal is further processed to create the specific odor maps. Microsc. Res. Tech. 58:135–141, 2002. © 2002 Wiley‐Liss, Inc.
PCR detection of clonal IgH and TCR gene rearrangements at the end of induction as a non-remission criterion in children with ALL: comparison with standard morphologic analysis and risk group classification.

BACKGROUND The initial response to induction therapy is currently considered one of the most important prognostic factors in acute lymphoblastic leukemias (ALL). A series of methods for the detection of submicroscopic levels of residual disease in patients with ALL mainly based on PCR and immunophenotyping has been developed, demonstrating that the presence of high levels of residual disease at the end of induction therapy is an important, independent prognostic factor. We determined the usefulness of PCR detection of minimal residual disease using consensus primers as a non-remission criterion. PROCEDURE Bone marrow samples obtained from 49 children with ALL were analyzed at diagnosis and at the end of induction therapy for the detection of clonal IgH, TCRdelta, and TCRgamma rearrangements by PCR. The results were compared with those obtained by standard morphologic analysis and risk group classification. RESULTS Patients who had clonality detected at the end of induction showed a significantly higher recurrence rate and lower event-free survival than those without detected clonality (24.9% vs. 89.7%) (P < 0.0001). Multivariate analysis revealed that detection of clonality at the end of induction was the most important, independent prognostic factor when associated with age, number of white blood cells, and immunophenotyping. CONCLUSIONS PCR detection of clonality using consensus primers is a relatively simple technique that is able to identify patients with a high chance of recurrence, and shows a higher sensitivity and a better prognostic value than standard morphologic analysis and risk group classification, defining a new remission criterion. However, further multicentric prospective studies using this technique employing a larger number of cases are necessary to confirm these findings.
Noonan syndrome – then and now

The report by Danetz, Donofrio and Embrey1 provides an interesting long term follow-up on the first patient diagnosed by me with what is now known as Noonan syndrome. In 1960, when this patient was seen, cardiac ultrasound was unavailable and left-sided cardiac catheterization uncommon. He had severe pulmonary stenosis, and did well following surgery. Unfortunately, his follow-up was not adequate and left-sided obstruction was not recognized until he became symptomatic some thirty years later. Early reports stressed the dysplastic pulmonary valve, with pulmonary stenosis as a common finding.2 By 1972, the report of Ehlers et al.3 brought attention to the left-sided involvement in the Turner phenotype.
Directivity of a planar hard-dielectric Fabry-Pérot optical ultrasound sensor

A planar hard-dielectric Fabry-Pérot (FP) optical ultrasound sensor was modelled analytically to study how different wave modes affect the directionality. The sensor was modelled as a multilayered structure using the global matrix method. Modal dispersion curves were extracted from the model to enable features of the directional response to be linked to specific wave phenomena. The analytical model showed good agreement with the measured directional response. The key features of the directional response are linked to wave effects such as the water-substrate and water-spacer compressional and shear critical angles. A region of high sensitivity immediately after the shear critical angle is associated with a leaky-Rayleigh wave which has a frequency-dependent phase speed. At higher frequencies, this region is diminished by a minimum which occurs when the mirrors have the same vertical displacement, resulting in a lack of sensitivity.
Reliability of isokinetic strength imbalance ratios measured using the Cybex NORM dynamometer

The main aim of this study was to examine the absolute and relative reliability of some commonly used strength imbalance indices such as concentric hamstring‐to‐concentric quadriceps ratio, eccentric hamstring‐to‐concentric quadriceps ratio and bilateral concentric and eccentric strength ratios. An additional aim was to examine the reliability of the peak torque and work of the knee extensor and flexor muscles measured using the Cybex NORM dynamometer. Eighteen physically active healthy subjects (mean ± standard deviation, age 23 ± 3 years, height 176 ± 5 cm, body mass 74 ± 8 kg) were tested three times with 96 h between sessions. Peak torque, average work, unilateral and bilateral ratios were determined at 60, 120, 180 and −60° s−1. Low (0·34) to moderate (0·87) relative reliability (intraclass correlation coefficient, ICC) was found for strength imbalance ratios with eccentric hamstring‐to‐concentric quadriceps ratio showing the greater ICC (>0·80). High ICC values (0·90–0·98) were found for peak torque and average work. Absolute reliability (standard error of measurement) ranged from 3·2% to 8·7% for strength imbalance ratios and from 4·3% to 7·7% for peak torque and average work measurements. This study established the reliability of the most common strength imbalance ratios and of absolute isokinetic muscle strength assessed using the Cybex NORM.
A case of advanced gastric cancer.

Dr. Ang: The patient is a 42-year-old man who developed abdominal discomfort, anorexia, and weight loss. The ensuing workup, performed at an outside institution, included an esophagogastroduo-denoscopy (EGD) that showed a 3 (cid:1) 7 cm ulcerated mass, located 37 cm from the incisors, in the distal gastric antrum. The mass was conﬁrmed on endoscopic ultrasound (EUS) and was staged as uT2N1 based on the presence of gastrohepatic lymphadenopathy measuring up to 1.6 cm in maximum diameter. A biopsy revealed a poorly differentiated adenocarcinoma with extensive ulceration and signet ring features. Staging computed tomography (CT) of the chest, abdomen, and pelvis showed marked soft tissue prominence of the gastric antrum and a small amount of free ﬂuid lateral to the right hepatic lobe. No intrahepatic lesions were seen, and the other abdominal organs were unremarkable. Given that the disease ap-peared localized, surgery was planned. Dr. Intlekofer: What is the appropriate staging algorithm for gastric cancer? Dr. Janjigian: The initial workup should consist of an EGD and EUS for localization and determination of tumor depth and regional lymph node involvement. I would also recommend a CT
A simplified ingestion procedure for esophageal capsule endoscopy: initial evaluation in healthy volunteers.

BACKGROUND AND STUDY AIMS Initial studies on esophageal capsule endoscopy (PillCam ESO) reported excellent sensitivity and specificity, but these were followed by mixed results in several subsequent studies, probably due to deviations from the recommended ingestion protocol and the inconvenience of capsule ingestion in the supine position. The aim of this study was therefore to test a simplified ingestion procedure (SIP) for PillCam ESO. PATIENTS AND METHODS Using a cross-over study design, the SIP was prospectively compared with the original ingestion procedure for PillCam ESO in 24 healthy volunteers (15 men, nine women; mean age 44, range 27 - 70) and evaluated for: bubbles/saliva interference at the Z-line, Z-line circumferential visualization (quadrants), and convenience and ease of the ingestion procedure. All Rapid 4 videos were reviewed in a randomized manner and read by an experienced PillCam ESO reader blinded to the ingestion procedure used. RESULTS It was found that the SIP significantly improved visualization in comparison with the original ingestion procedure, with less interference due to bubbles/saliva observed at the gastroesophageal junction ( P = 0.002) and improved visualization of the Z-line ( P = 0.025). Although the esophageal transit time was significantly faster with the SIP (3 : 45 min vs. 0 : 38 min; P = 0.0001), there were no differences in the number of Z-line frames/images captured. CONCLUSIONS This new, simplified ingestion procedure for PillCam ESO provides significantly improved visualization of the Z-line in healthy volunteers. The overall test characteristics of PillCam ESO using SIP should be tested in patients with esophageal disease.
Abstention in the general population of the U.S.A.

Summary Data on abstention from a 1979 general population survey in the U.S.A. were analyzed and compared to data from a similar 1964 survey. Trend comparisons for the 15 year interval revealed few changes in abstention rates among various demographic categories. There was no evidence that the difference between male and female abstention rates has narrowed, that a more abstemious older generation is being replaced by a less abstemious younger generation, that there has been a regional convergence of abstention rates, or that the influence of religion on abstention has declined. A cluster analysis of reasons for abstaining (among lifelong abstainers) identified four sets of reasons: moral objection to drinking, dislike of the consequences of drinking, ‘inconsequential’ reasons, and abstinent family background. Compared to drinkers, abstainers consistently and significantly tended to disapprove of drinking by others in a variety of situational contexts. Militancy on these issues was stronger among abstainers from dry regions and among abstainers who were fundamentalist Protestants. Militancy was not, however, related to age or education. Lifelong abstainers who cited moral reasons for abstaining were more militant than those who did not.
The Interaction of Angular and Linear Optokinetic Stimuli with an Angular Vestibular Stimulus

In this paper we investigate the selectivity of angular and linear optokinetic (OK) stimuli in modulating angular vestibular nystagmus in man. This was prompted by the existence of different vection illusions occurring with linear and angular visual stimuli and by the observation that slow buildup of OK nystagmus with some cerebellar and parietal lesions occurs with angular but not with linear OK stimuli. ' Optokinetic-vestibular interaction was assessed by means of sequential stimuli; a prolonged OK stimulus was followed immediately by a vestibular stimulus in the dark. The linear or angular OK stimuli moved rightwards or leftwards for 30 seconds at constant velocity (20"/second). At this point the lights were extinguished and, simultaneously, the chair started rightwards rotation (a 20"/second velocity step immediately followed by constant acceleration at l.S"/second per second for 17 seconds, FIGURE 1). The rotational stimulus was designed to counteract the normal exponential decay of vestibular nystagmus and maintain a relatively constant eye velocity. Ten normal adult subjects took part in the experiment and viewed passively OK stripes at intervals of 9" at a distance of 0.8 meters provided by a motorized full-field drum or a linear screen (subtending 74" of vertical; 70" of vertical and 86" of horizontal visual angle respectively). Three vestibular stimuli alone in each subject provided a baseline with which to compare the interaction of the vestibular-OK responses. Eye movements were recorded by DC electrooculography (EOG) and displayed upon an ink jet recorder. Sequential responses of slow phase eye velocity (SPV) were measured by a semiautomated procedure from the onset of the vestibular stimulus. Differences in mean SPV between paradigms were assessed by one-way analysis of variance using Dunnett's multiple comparison procedure. As shown in FIGURE 2, when the preceding OK stimuli were in the opposite direction to the rotational stimulus ("summating SPV"), the initial SPV of the vestibular response was increased; when the OK and rotational stimuli were in the same direction ("opposing SPV"), SPV was reduced. This effect was larger and more prolonged with angular than with linear OK stimuli; statistical differences (p < 0.05) between additive and opposing angular OK stimuli lasted up to 15 seconds but for only 1.25 seconds with the linear OK stimuli. The mean time to return to "baseline" vestibular values with opposing vestibular-OK stimuli was 12 seconds for an angular OK stimulus, which was significantly longer (p < 0.004) than the 4 seconds taken by the linear OK stimulus. As shown in previous studies: opposing responses had a stronger effect than summating responses (FIGURE 2). In conclusion, the modulation of rotational vestibular nystagmus is larger and
Thigh grafts contribute significantly to patients' time on dialysis.

BACKGROUND AND OBJECTIVES Thigh grafts are placed in hemodialysis patients who have exhausted all arm access sites. The goal of this study was to compare the survival, complication rates, and overall contribution of thigh grafts with arm grafts and fistulas in patients with at least one functional thigh graft during their dialysis history. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This longitudinal review of a prospectively acquired clinical database included 85 thigh graft recipients. The rates of survival, thrombosis, infection, and other complications were determined for a total of 268 fistulas, arm grafts, and thigh grafts placed in these patients. RESULTS In this patient subset, thigh graft primary failure rate was lower than arm grafts and fistulas (3 versus 13 and 61%, respectively). Excluding primary failures, thigh grafts survived longer than both arm grafts and mature fistulas (53 versus 14 and 32%, at 3 years; 47 versus 3 and 11% at 5 years). Thigh grafts had a lower thrombosis rate than arm grafts (0.543 versus 1.457/patient-year) but similar rates of loss as a result of infection and surgical revision. In patients with previous arm accesses, thigh grafts contributed 51% of total dialysis time compared with 38 and 11% for arm grafts and fistulas. CONCLUSIONS Thigh grafts provide long-term, thrombosis- and infection-free dialysis access for patients with exhausted arm access sites. The decision for thigh graft placement should, therefore, be made as soon as there is evidence for unavailability of arm access sites so that catheter use can be minimized.
The expanding family of interleukin‐1 cytokines and their role in destructive inflammatory disorders

Understanding cytokine immunobiology is central to the development of rational therapies for destructive inflammatory diseases such as rheumatoid arthritis (RA) and periodontitis. The classical interleukin‐1 (IL‐1) family cytokines, IL‐1α and IL‐1β, as well as IL‐18, play key roles in inflammation. Recently, other members of the IL‐1 family have been identified. These include six cytokines whose genes are located downstream of the genes for IL‐1α and IL‐1β on chromosome 2 (IL‐1F5‐10) and also IL‐33, which is the ligand for ST2, a member of the IL‐1R/Toll‐like receptor (TLR) receptor superfamily. IL‐1F6, IL‐1F8 and Il−1F9 are agonists and, along with their receptor IL‐1Rrp2, are highly expressed in epithelial cells suggesting a role in immune defence in the skin and the gastrointestinal (GI) tract including the mouth. Synovial fibroblasts and articular chondrocytes also express IL‐1Rrp2 and respond to IL‐1F8, indicating a possible role in RA. IL‐33 is associated with endothelial cells in the inflamed tissues of patients with RA and Crohn's disease, where it is a nuclear factor which regulates transcription. IL‐33 is also an extracellular cytokine: it induces the expression of T helper 2 (Th2) cytokines in vitro and in vivo as well as histopathological changes in the lungs and GI tract of mice. Therapeutic agents which modify IL‐1 cytokines (e.g. recombinant IL‐1Ra) have been used clinically and others are at various stages of development (e.g. anti‐IL‐18 antibodies). This review highlights the emerging data on these novel IL‐1 cytokines and assesses their possible role in the pathogenesis and therapy of destructive inflammatory disorders such as RA and periodontitis.
CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

CT7 (MAGE‐C1) is a member of the cancer testis (CT) antigen family. The present study describes the generation of CT7‐33, a monoclonal antibody (MAb) to CT7, and the preliminary protein expression analysis of CT7 in normal tissues and in a limited number of neoplastic lesions. CT7‐33 was effective in frozen as well as formalin‐fixed, paraffin‐embedded tissues, and immunohistochemistry/reverse transcriptase polymerase chain reaction (RT‐PCR) co‐typing demonstrated antibody specificity. CT7‐33 immunoreactivity in normal adult tissues is restricted to testicular germ cells. In neoplastic lesions, CT7‐33 immunostaining is confined to tumor cells, and the frequency of CT7 protein expression mostly parallels previous mRNA analyses. Whereas colorectal and renal cell carcinomas, as well as sarcomas, exhibit poor or no CT7‐33 staining, carcinomas of the mammary gland and ovary, nonsmall cell lung carcinoma and metastatic melanomas exhibit a high incidence of CT7 protein expression. However, as seen in previous analyses of other CT antigens, the expression pattern is mostly heterogeneous, and tumors with more than 50% of tumor staining are only infrequently encountered. In summary, our study presents a new serologic reagent for the analysis of CT7 on a protein level and confirms what is known with regard to the expression pattern of other CT antigens in tumors: frequent heterogeneity of antigen expression. © 2002 Wiley‐Liss, Inc.