Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of novel paraja ring finger 2‐fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non‐small cell lung cancer

Previously, we reported that the overexpression of fer tyrosine kinase (FER), a non‐receptor tyrosine kinase, is correlated with poor postoperative prognosis and cancer‐cell survival in non‐small cell lung cancer (NSCLC). In the present study, we further analyzed FER‐overexpressed NSCLC cases and identified various patterns of chimeric mRNAs, composed of paraja ring finger 2 (PJA2) and FER. We detected no genomic rearrangements between PJA2 and FER and attributed these chimeric mRNAs to alterations at the transcriptome level: i.e., trans‐splicing. Several chimeric patterns were detected concurrently in each patient, and the pattern sets varied among patients, although the pattern in which PJA2 exon 1 was fused to FER exon 3 (designated as Pe1‐Fe3 mRNA) was detected constantly. Therefore, in a wide screening for PJA2‐FER mRNAs in NSCLC, we focused on this chimeric pattern as a representative chimera. In analyses of 167 NSCLC samples, Pe1‐Fe3 mRNA was identified in about 10% of the patients, and the presence of chimeric mRNA was significantly correlated with a high expression level of parental FER mRNA. Furthermore, we found that the detection of Pe1‐Fe3 mRNA was correlated with poor postoperative survival periods in NSCLC, consistent with a previous finding in which FER overexpression was correlated with poor postoperative prognosis in NSCLC. This report is the first to suggest a correlation between chimeric mRNA and the expression level of parental mRNA. Furthermore, our findings may be clinically beneficial, suggesting that PJA2‐FER mRNAs might serve as a novel prognostic biomarker in NSCLC.
A PBPK Modeling Assessment of the Competitive Metabolic Interactions of JP-8 Vapor with Two Constituents, m-Xylene and Ethylbenzene

Jet Propellant 8 (JP-8) is a kerosene-based jet fuel used in the military and is composed of hundreds of hydrocarbons. A PBPK model was developed to assess the metabolic interactions of JP-8 vapor on two prominent constituents of JP-8 vapor, m-xylene (XYL) and ethylbenzene (EBZ). A limited number of rats were exposed to JP-8 vapor in a Leach chamber for 4 h to 380, 1100, or 2700 mg/m3 (total hydrocarbon). Several individual hydrocarbons were monitored in the chamber atmosphere, including XYL, EBZ, and the total hydrocarbon concentration. Blood and liver were harvested and analyzed by a novel headspace SPME/GC-MS method that allowed for identification of individual hydrocarbons and low limits of detection. The PBPK model was able to describe the metabolic interactions between XYL, EBZ, and a lumped aromatic fraction of JP-8 vapor estimated to be 18 to 25% of the fuel vapor. Competitive inhibition of XYL and EBZ metabolism was observed for JP-8 vapor inhalation exposures of 1100 and 2700 mg/m3. Future inhalation studies with jet fuel include aerosol exposures and expansion of the PBPK models to include other hydrocarbons such as n-alkanes and upper respiratory tract dosimetry of aerosol droplets.
Targeting the epidermal growth factor receptor by erlotinib (Tarceva™) for the treatment of esophageal cancer

Esophageal cancer is the sixth most common cause of cancer‐related death worldwide. Because of very poor 5‐year survival new therapeutic approaches are mandatory. Erlotinib (Tarceva™), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR‐TK), potently suppresses the growth of various tumors but its effect on esophageal carcinoma, known to express EGFR, remains unexplored. We therefore studied the antineoplastic potency of erlotinib in human esophageal cancer cells. Erlotinib induced growth inhibition of the human esophageal squamous cell carcinoma (ESCC) cell lines Kyse‐30, Kyse‐70 and Kyse‐140, and the esophageal adenocarcinoma cell line OE‐33, as well as of primary cell cultures of human esophageal cancers. Combining erlotinib with the EGFR‐receptor antibody cetuximab, the insulin‐like growth factor receptor tyrosine kinase inhibitor tyrphostin AG1024, or the 3‐hydroxy‐3‐methylglutaryl coenzyme. A reductase (HMG‐CoAR) inhibitor fluvastatin resulted in additive or even synergistic antiproliferative effects. Erlotinib induced cell cycle arrest at the G1/S checkpoint. The erlotinib‐mediated signaling involved the inactivation of EGFR‐TK and ERK1/2, the upregulation of the cyclin‐dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. However, erlotinib did not induce immediate cytotoxicity or apoptosis in esophageal cancer cells. The inhibition of EGFR‐TK by erlotinib appears to be a promising novel approach for innovative treatment strategies of esophageal cancer, as it powerfully induced growth inhibition and cell cycle arrest in human esophageal cancer cells and enhanced the antineoplastic effects of other targeted agents. © 2005 Wiley‐Liss, Inc.
Clinical disposition, metabolism and in vitro drug–drug interaction properties of omadacycline

Abstract 1. Absorption, distribution, metabolism, transport and elimination properties of omadacycline, an aminomethylcycline antibiotic, were investigated in vitro and in a study in healthy male subjects. 2. Omadacycline was metabolically stable in human liver microsomes and hepatocytes and did not inhibit or induce any of the nine cytochrome P450 or five transporters tested. Omadacycline was a substrate of P-glycoprotein, but not of the other transporters. 3. Omadacycline metabolic stability was confirmed in six healthy male subjects who received a single 300 mg oral dose of [14C]-omadacycline (36.6 μCi). Absorption was rapid with peak radioactivity (∼610 ngEq/mL) between 1–4 h in plasma or blood. The AUClast of plasma radioactivity (only quantifiable to 8 h due to low radioactivity) was 3096 ngEq h/mL and apparent terminal half-life was 11.1 h. Unchanged omadacycline reached peak plasma concentrations (∼563 ng/mL) between 1–4 h. Apparent plasma half-life was 17.6 h with biphasic elimination. Plasma exposure (AUCinf) averaged 9418 ng h/mL, with high clearance (CL/F, 32.8 L/h) and volume of distribution (Vz/F 828 L). No plasma metabolites were observed. 4. Radioactivity recovery of the administered dose in excreta was complete (>95%); renal and fecal elimination were 14.4% and 81.1%, respectively. No metabolites were observed in urine or feces, only the omadacycline C4-epimer.
Are frailty markers associated with serious thoracic and spinal injuries among motor vehicle crash occupants?

BACKGROUND While age is a known risk factor in trauma, markers of frailty are growing in their use in the critically ill. Frailty markers may reflect underlying strength and function more than chronologic age, as many modern elderly patients are quite active. However, the optimal markers of frailty are unknown. METHODS A retrospective review of The Crash Injury Research and Engineering Network (CIREN) database was performed over an 11-year period. Computed tomographic images were analyzed for multiple frailty markers, including sarcopenia determined by psoas muscle area, osteopenia determined by Hounsfield units (HU) of lumbar vertebrae, and vascular disease determined by aortic calcification. RESULTS Overall, 202 patients were included in the review, with a mean age of 58.5 years. Median Injury Severity Score was 17. Sarcopenia was associated with severe thoracic injury (62.9% vs. 42.5%; p = 0.03). In multivariable analysis controlling for crash severity, sarcopenia remained associated with severe thoracic injury (p = 0.007) and osteopenia was associated with severe spine injury (p = 0.05). While age was not significant in either multivariable analysis, the association of sarcopenia and osteopenia with development of serious injury was more common with older age. CONCLUSIONS Multiple markers of frailty were associated with severe injury. Frailty may more reflect underlying physiology and injury severity than age, although age is associated with frailty. LEVEL OF EVIDENCE Prognostic and epidemiologic study, level IV.
THE RELATIONSHIP AMONG DONOR‐RECIPIENT HLA MISMATCHES, REJECTION, AND DEATH FROM CORONARY ARTERY DISEASE IN CARDIAC TRANSPLANT RECIPIENTS1

Review of 448 cyclosporine-treated heart transplant recipients was undertaken to examine the relationship of donor-recipient HLA compatibility to patient survival, rejection, and death from coronary artery disease (CAD). Pre-Tx crossmatching and panel-reactive antibody (PRA) were correlated to survival as well. Overall patient survivals were 78%, 70%, and 65% at 1, 3, and 5 years post-Tx, respectively. Matching of donor-recipient HLA did not improve outcome in that 1, 3, and 5 year survivals for well-matched (≤2 A, B, or 0–1DR mismatches [MMs]) vs. poorly matched (>2 A, B, or 2 DR MMs) recipients were comparable and not significantly different. Well-matched recipients, however, experienced significantly fewer rejections (1.06±1.2 vs. 1.96±1.0, P<0.01 for ≤2 A, B MMs vs. >2A, B MMs and 1.1±0.9 vs. 2.0±1.1 for 0–1 DR MMs vs. 2 DR MMs, P<0.01). Moreover, HLA-DR, but not HLA A, B, was a significant (P<0.01) predictor of early rejection (<30 days) in that 65% (165/254) of poorly matched vs. only 40% (95/194) of well-matched HLA-DR recipients experienced early rejections. Interestingly, an inverse relationship was found between HLA A and B MM, but not HLA-DR MM, and death from coronary artery disease in that 17% (19/111) of well-matched vs. 9% (32/327) of poorly matched patients died from CAD. Pre-Tx PRA did not impact patient survival or rejection. Donor-recipient crossmatching was performed utilizing the NIH and/or antiglobulin (AHG) procedures. No survival differences were observed at 1, 2, and 3 years post-Tx when comparing outcome for the 24 NIH cross-match (XM)-positive (+) with the 424 NIH-XM-nega-tive patients. Only 10 patients (10/125 AHG-tested recipients) displayed a positive AHG recipient antidonor reactivity. When these 10 AHG-XM (+) sera were treated with dithioerythritol (to inactivate IgM) all 10 converted to a negative reactivity, indicating that a positive crossmatch due to IgM reactivity should not be considered a contraindication to cardiac transplantation. These data also suggest that the reactivity of the 24 NLH-XM(+) sera were most likely due to IgM, and that poorly matched heart recipients may benefit from a more aggressive immunosuppressive regimen to prevent early rejections.
Transient Arrest of Germinal Vesicle Breakdown Improved In Vitro Development Potential of Buffalo (Bubalus Bubalis) Oocytes

Germinal vesicle breakdown (GVBD) is the first milestone that an oocyte needs to achieve toward completing the maturation and gaining potential to fertilize. Significantly lower in vitro embryo production rate in buffaloes can be attributed to heterogeneity of GVBD occurrence among oocytes obtained from abattoir derived ovaries. Evidence from our earlier work had suggested that different qualities of buffalo oocytes differ significantly in their timing of GVBD. Besides, these oocytes also differ in terms of volume of Akt phosphorylation, which initiates the process of GVBD. With objective of synchronizing the oocytes for GVBD, immature buffalo oocytes were subjected to a two‐step culture protocol, initially in the presence of GVBD inhibitors and subsequently, in vitro maturation (IVM) with added SC79 (activates Akt). Expression of developmentally important genes was assessed along with embryo development rate and blastocyst health to interpret the consequences. Oocytes subjected to a short GVBD inhibition period of 6 h followed by IVM with SC79 resulted in improved cleavage and blastocyst rates. Resultant blastocysts also possessed higher ICM: TE ratio. Further, GVBD inhibited oocytes displayed a sustained cytoplasmic maturation status in terms of reorganization of cortical granules (CGs), mitochondrial membrane potential, and glutathione levels during the period of inhibition. We conclude that a temporary GVBD arrest of buffalo oocytes and modulation of Akt improves the in vitro embryo development rate as well as quality of resultant embryos. Besides, our meiotic arrest protocol does not affect the cytoplasmic maturation. J. Cell. Biochem. 119: 278–289, 2018. © 2017 Wiley Periodicals, Inc.
O-Displaying: an orientation-based augmented reality display on a smart glass with a user tracking from a depth camera

Augmented reality (AR) contents are widely viewed from mobile devices, e.g. smart phones, tablets, and smart glasses [Olsson and Salo 2011]. To properly display AR contents on a screen, color cameras are widely used to detect markers, feature points, and registered images [Krevelen 2007], and the corresponding 2D/3D visual contents are rendered with proper size and location on the screen/displaying device. However, when the lighting condition is unstable, the flicking effects of the rendered visual contents could degrade the user experience. In a dark environment, it is challenging to display AR contents based on color cameras for marker/feature point detection. Even RGB-D cameras [A. Canessa and Solari 2014] are used for object detection to display the AR contents, the object without salient representation in the depth map are still challenging to be detected. In addition, the motion blur situation also makes the AR content displaying challenging. To solve the above-mentioned issues, in this paper, we propose an orientation-based AR display scheme using the orientation sensors, i.e. gyro sensor, accelerometer, and magnetometer (compass sensor) of a smart glass, according to the user tracking results from a depth camera to properly display the AR contents on a smart glass. In the experimental results, the proposed prototype can properly display AR contents in bright environment and in extremely dark environment.
The effect of extended calving intervals in high-yielding lactating cows on milk production and profitability.

A field trial was conducted to examine the effect of extended calving interval (CI) on production and profitability of high yielding cows (n = 937). First insemination was performed at 154 and 93 d postpartum (pp), for treatment and control primiparous cows, respectively, and at 124 and 71 d pp for treatment and control multiparous cows, respectively. During the first experimental lactation, average daily value-corrected milk (VCM) yield was 28.5 and 27.7 kg/d of CI for treatment (n = 131) and control (n = 133) primiparous cows, respectively. No significant difference in average daily VCM yield (33.0 and 32.8 kg/d of CI) was found between treatment (n = 271) and control (n = 215) multiparous cows . In the first 150 d of the subsequent lactation, there were significant differences in milk and VCM production in favor of the treatment primiparous cows (41.4 vs. 39.7 kg of VCM/d) but no significant differences in the production of multiparous cows. Primiparous and multiparous cows with extended lactations were more profitable. During the first experimental lactation, there were advantages of $0.19 and $0.12/d of CI in the net returns for primiparous cows and multiparous cows with longer CI, respectively. When the economic analysis included the first experimental lactation plus the first 150 d of the subsequent one, the net return per day of CI was higher for cows with an extended voluntary waiting period: $0.21/d and $0.16/d for primiparous and multiparous cows, respectively. A delay of 60 d with respect to the usual voluntary waiting period in the beginning of inseminations of high yielding cows has economic advantages and allows the farmer an option for decisions regarding individual cows.
A Simplified Network Access Control Design and Implementation for M2M Communication Using SDN

Network access control is an established security method that only grants access to authorised devices. The 802.1X standard defines the mechanisms for implementing network access control in legacy networks. However, its implementation requires hardware and software components that are not commonly found in small deployments and also adds to the complexity of the network and the deployment time. The Software- defined Networking (SDN) offers an opportunity to develop new network access control solutions, among other things, that can be used to simplify and speed up the implementation and deployment of small, localised sensor networks. In this paper we demonstrate how SDN can be used to develop a basic network access control service without using 802.1X software and hardware while also offering the ability to adjust the available bandwidth and network access policy per device. The proposed solution provides quick and flexible network deployments for IoT sensor networks and other types of M2M communication. We implement our proposed architecture using OpenDaylight and OpenFlow switches and evaluate its performance by running tests with multiple client devices and various policies. Our results show that the studied approach can be a valid approach for small to medium sized networks that requires quick and low- cost deployment and high flexibility in terms of adding new devices.
Complete sequencing of the Fugu WAGR region from WT1 to PAX6: dramatic compaction and conservation of synteny with human chromosome 11p13.

The pufferfish Fugu rubripes has a genome approximately 7.5 times smaller than that of mammals but with a similar number of genes. Although conserved synteny has been demonstrated between pufferfish and mammals across some regions of the genome, there is some controversy as to what extent Fugu will be a useful model for the human genome, e.g., [Gilley, J., Armes, N. & Fried, M. (1997) Nature (London) 385, 305-306]. We report extensive conservation of synteny between a 1.5-Mb region of human chromosome 11 and <100 kb of the Fugu genome in three overlapping cosmids. Our findings support the idea that the majority of DNA in the region of human chromosome 11p13 is intergenic. Comparative analysis of three unrelated genes with quite different roles, WT1, RCN1, and PAX6, has revealed differences in their structural evolution. Whereas the human WT1 gene can generate 16 protein isoforms via a combination of alternative splicing, RNA editing, and alternative start site usage, our data predict that Fugu WT1 is capable of generating only two isoforms. This raises the question of the extent to which the evolution of WT1 isoforms is related to the evolution of the mammalian genitourinary system. In addition, this region of the Fugu genome shows a much greater overall compaction than usual but with significant noncoding homology observed at the PAX6 locus, implying that comparative genomics has identified regulatory elements associated with this gene.
Bone formation with various bone graft substitutes in critical-sized rat calvarial defect.

OBJECTIVE This histomorphometric study compared the efficacy of a new bone graft substitute (N-HA) derived from hen eggshell, consisted of submicron scale porous hydroxyapatite structure, in the healing of 8 mm diameter critical size defects in rat calvaria. We compared N-HA alone or in combination with calcium sulfate (CS), with a commercial bone substitute, anorganic bovine bone (Bio-Oss, BO). MATERIAL AND METHODS Critical size defects were created in calvaria of 56 adult Sprague-Dawley rats. Animals were divided into four groups and treated with (1) unfilled defects, (2) N-HA grafts, (3) BO grafts and (4) N-HA/CS grafts. The percentage of new bone formed (NB%) was evaluated histomorphometrically after 6 and 12 weeks. RESULTS The N-HA group exhibited more new bone formation compared with other groups at 6 and 12 weeks. Histomorphometric analysis showed greater NB% in N-HA group (11.2% at 4 weeks and 19.2% at 12 weeks) compared with those in unfilled (3.9% at 6 weeks and 6.4% at 12 weeks), BO-treated (6.4% at 6 weeks and 8.2% at 12 weeks) and N-HA/CS-treated (6.3% at 6 weeks and 12.6% at 12 weeks) groups. The N-HA group showed significant differences in NB% compared with unfilled group at 6 weeks (P=0.016), unfilled and BO-treated groups at 12 weeks (P=0.001). The addition of CS did not enhance the NB% compared with defects grafted with N-HA alone. CONCLUSION N-HA was an osteoconductive bone substitute for treating osseous defects in critical size defects of rat calvaria.
Binary linear programming formulation of the access selection problem in multi-service and heterogeneous network environments

In this paper we model access selection in heterogeneous access network environments as a binary linear optimization problem. The model is based on a flexible utility function, which allows the integration of various parameters of merit. One of the major advantages of our proposal is that it considers both the willingness of the end-users to have connectivity just in particular moments (according to the corresponding service patterns), as well as the historical evolution of such services (outcome of earlier problem instances). We assess the feasibility of the proposed method with an illustrative network deployment, embracing both heterogeneous technologies and two services, with different requirements and characteristics. The results show that an appropriate selection of the utility function is of outer relevance to clearly understand the goodness of the obtained performance.
Der Kansas City Cardiomyopathy Questionnaire (KCCQ) - ein neues krankheitsspezifisches Messinstrument zur Erfassung der Lebensqualität bei chronischer Herzinsuffizienz

: Patients' health-related quality of life is increasingly being included as an additional endpoint when evaluating the treatment of chronic heart failure. Although generic self-report instruments measuring health-related quality of life are available, there is a lack of disease-specific instruments covering various dimensions of quality of life with high reliability, validity and sensitivity to chance. Thus, the aim of the present study was to evaluate the German version of a new heart failure-specific quality of life measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ). The sample consisted of 233 consecutively recruited outpatients of a university department in Germany. Test-retest-reliability was high (intraclass correlation coefficient 0.93 for both the Functional State and the Clinical Summary total scores). Construct validity was demonstrated with strong correlations to respective subscales of the SF-36. Known groups validity was shown by both statistically and clinically significant differences between NYHA classes. The examination of sensitivity to change yielded promising results. The questionnaire was well accepted by the participating patients. The KCCQ proved to be a reliable and valid self-report instrument for measuring disease-specific quality of life in chronic heart failure.