bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sildenafil improves vascular endothelial function in patients with cystic fibrosis
Authors: Rodriguez-Miguelez Paula , Lee Nichole , Tucker Matthew A. , Csányi Gábor , McKie Kathleen T. , Forseen Caralee , Harris Ryan A. 
Published: August 2018

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.
Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors
Authors: Romero-Calvo Isabel , Weber Christopher R. , Ray Mohana , Brown Miguel , Kirby Kori , Nandi Rajib K. , Long Tiha M. , Sparrow Samantha M. , Ugolkov Andrey , Qiang Wenan , Zhang Yilin , Brunetti Tonya , Kindler Hedy , Segal Jeremy P. , Rzhetsky Andrey , Mazar Andrew P. , Buschmann Mary M. , Weichselbaum Ralph , Roggin Kevin , White Kevin P. 
Published: August 2018

Abstract

Patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid systems show great promise for understanding the biological underpinnings of disease and advancing therapeutic precision medicine. Despite the increased use of organoids, the fidelity of molecular features, genetic heterogeneity, and drug response to the tumor of origin remain important unanswered questions limiting their utility. To address this gap in knowledge, primary tumor- and patient-derived xenograft (PDX)-derived organoids, and 2D cultures for in-depth genomic and histopathologic comparisons with the primary tumor were created. Histopathologic features and PDAC representative protein markers (e.g., claudin 4 and CA19-9) showed strong concordance. DNA- and RNA-sequencing (RNAseq) of single organoids revealed patient-specific genomic and transcriptomic consistency. Single-cell RNAseq demonstrated that organoids are primarily a clonal population. In drug response assays, organoids displayed patient-specific sensitivities. In addition, the in vivo PDX response to FOLFIRINOX and gemcitabine/abraxane treatments were examined, which was recapitulated in vitro with organoids. This study has demonstrated that organoids are potentially invaluable for precision medicine as well as preclinical drug treatment studies because they maintain distinct patient phenotypes and respond differently to drug combinations and dosage.

Implications:
The patient-specific molecular and histopathologic fidelity of organoids indicate that they can be used to understand the etiology of the patient's tumor and the differential response to therapies and suggests utility for predicting drug responses.
Solar Disturbances and Interdiurnal Variations of Atmospheric Pressure*
Authors: Huntington Ellsworth 
Published: August 2018

Summary
The conclusion is that interdiurnal variability of atmospheric pressure at New Haven appears to show a mathematically significant correlation with the position of sunspots on the disk of the sun as seen from the earth. The correlation indicates a double annual cycle in which high latitude of spots is associated with high barometric variability in summer and winter at about the time of the solstices and with low barometric variability in the spring and fall near the time when one or the other axis of the sun points most nearly to the earth. Whether the relationship thus suggested is thermal or electrical, or whether it has any causal connection with the axes of either the earth or the sun, we do not know. The important fact is that this first investigation of the latitude of sunspots in relation to barometric variability suggests that a hidden, and perhaps hitherto unrecognized factor, manifested in the form of the latitudinal location of sunspots, is somehow imposed upon the terrestrial factors which lead to interdiurnal changes of barometric pressure.
The Long-Period Variations in the Length of the 11-Year Solar Period, and Concurrent Variations in Terrestrial Phenomena
Authors: Clough H. W. 
Published: August 2018

Synopsis
Long-period variations in solar phenomena are shown by the relative numbers at epochs of maxima and the intervals between successive maxima or minima. Intensity values are available only from 1750, or the date of the beginning of the Wolfer relative numbers. The interval values are derived from the Wolfer epochs from 1611 and from the epochs of maxima beginning 301 A.D., first derived by Fritz and revised by the writer. There is a high negative correlation between the intensity at a maximum and the interval from the preceding minimum.
The epochs of maximum and minimum auroral frequency, available since 1611, and of magnetic declination range since 1775, afford an independent check on the reliability of the Wolfer epochs. A change in two of the epochs of maxima is suggested.
The reliability of the Fritz ancient epochs is confirmed by a graphical device, showing the continuity of the 11-year epochs since 301.
The existence of long-period variations in the length of the 11-year period is shown by a graphical periodicity tabulation of the 11-year intervals since 301. A 37-year period is shown by the existence of maxima every third or fourth interval, and an 83-year period is shown by a similar tabulation of the smoothed intervals. These periods are also obtained by the rigid method of self-correlation of the 11-year intervals, and numerous series of terrestrial data yield by self-correlation the same periods. The meteorological effects following certain solar changes are briefly summarized.
Transmission of the Total and the Infrared Component of Solar Radiation Through a Smoky Atmosphere
Authors: Hand Irving F. 
Published: August 2018

SUMMARY
Immediately before and during the passage of a smoke cloud from forest fires, simultaneous measurements were made of total normal incidence solar radiation and that portion of the solar spectrum longer than 0.7μ. Calculations made of the relative amount of radiation that should be received for both the total and limited components checked closely with the ratios between measurements with a smoke-free atmosphere but showed variance with ratios obtained in the presence of smoke. The range between the maximum and minimum values of total radiation during a ten-minute period in the presence of smoke was 2.3 times as great as the range between the maximum and minimum values of infrared radiation; from which we conclude, as theory implies, that long-wave radiation passes much more freely through an atmosphere containing particles slightly less than one micron in diameter than does the shorter, or visible and ultraviolet radiation.
Efficacy of Afternoon Plerixafor Administration for Stem Cell Mobilization
Authors: El Rahi Cynthia , Cox James Eldin , May Romelia , Carrum George , Anyadike Gloria Obi , Scholoff Audrey , Kamble Rammurti 
Published: August 2018

Background: When used for hematopoietic stem cell mobilization, plerixafor was originally recommended to be administered 11 hours prior to apheresis based on the peak effect of 10 to 14 hours translating into an administration time of 10 to 11 pm. Reports of post-plerixafor anaphylactic reactions mandated labeling change by the Food and Drug Administration with recommendation of monitoring patients after administration. Based on data suggesting sustained plerixafor activity at 18 hours, we changed our administration time to 4 pm at our center. Objective: The objective of this study is to compare the stem cell collection efficiency before and after the practice change at our institution. Methods: A retrospective chart review for patients with multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma who received a plerixafor-containing mobilization regimen was conducted. The primary end point was the percentage of patients achieving the minimal CD34+ cell goal in ⩽2 apheresis days. The secondary end points included the percentage of patients achieving the preferred CD34+ cell goal in ⩽2 apheresis days, days of apheresis, total CD34+ cells Collected, and engraftment time. Results: A total of 208 patients (4 pm group n = 68, 10 pm group n = 140) with multiple myeloma (n = 112), Hodgkin lymphoma (n = 10), and non-Hodgkin lymphoma (n = 86) were included in the analysis. About 91% and 89% ( P = .804) of the patients in the 4 and 10 pm groups, respectively, collected minimum cell dose. Preferred CD34+ cell goal was achieved in 57% and 53% of patients in the 4 and 10 pm groups, respectively. Conclusions: Late afternoon administration of plerixafor provides efficient stem cell mobilization.
Computation of dry-rock VP/VS ratio, fluid property factor, and density estimation from amplitude-variation-with-offset inversion
Authors: Chen Gang , Wang Xiaojun , Wu Baocheng , Qi Hongyan , Xia Muming 
Published: August 2018

Estimating the fluid property factor and density from amplitude-variation-with-offset (AVO) inversion is important for fluid identification and reservoir characterization. The fluid property factor can distinguish pore fluid in the reservoir and the density estimate aids in evaluating reservoir characteristics. However, if the scaling factor of the fluid property factor (the dry-rock [Formula: see text] ratio) is chosen inappropriately, the fluid property factor is not only related to the pore fluid, but it also contains a contribution from the rock skeleton. On the other hand, even if the angle gathers include large angles (offsets), a three-parameter AVO inversion struggles to estimate an accurate density term without additional constraints. Thus, we have developed an equation to compute the dry-rock [Formula: see text] ratio using only the P- and S-wave velocities and density of the saturated rock from well-logging data. This decouples the fluid property factor from lithology. We also developed a new inversion method to estimate the fluid property factor and density parameters, which takes full advantage of the high stability of a two-parameter AVO inversion. By testing on a portion of the Marmousi 2 model, we find that the fluid property factor calculated by the dry-rock [Formula: see text] ratio obtained by our method relates to the pore-fluid property. Simultaneously, we test the AVO inversion method for estimating the fluid property factor and density parameters on synthetic data and analyze the feasibility and stability of the inversion. A field-data example indicates that the fluid property factor obtained by our method distinguishes the oil-charged sand channels and the water-wet sand channel from the well logs.
Positive Work Contribution Shifts from Distal to Proximal Joints during a Prolonged Run
Authors: SANNO MAXIMILIAN , WILLWACHER STEFFEN , EPRO GASPAR , BRÜGGEMANN GERT-PETER 
Published: August 2018

ABSTRACT

Purpose
To investigate the joint-specific contributions to the total lower-extremity joint work during a prolonged fatiguing run.

Methods
Recreational long-distance runners (n = 13) and competitive long-distance runners (n = 12) performed a 10-km treadmill run with near-maximal effort. A three-dimensional motion capture system synchronized with a force-instrumented treadmill was used to calculate joint kinetics and kinematics of the lower extremity in the sagittal plane during the stance phase at 13 distance points over the 10-km run.

Results
A significant (P < 0.05) decrease of positive ankle joint work as well as an increase of positive knee and hip joint work was found. These findings were associated with a redistribution of the individual contributions to total lower-extremity work away from the ankle toward the knee and hip joint which was more distinctive in the recreational runner group than in the competitive runner group. This redistribution was accomplished by significant (P < 0.05) reductions of the external ground-reaction force lever arm and joint torque at the ankle and by the significant (P < 0.05) increase of the external ground-reaction force lever arm and joint torque at the knee and hip.

Conclusions
The redistribution of joint work from the ankle to more proximal joints might be a biomechanical mechanism that could partly explain the decreased running economy in a prolonged fatiguing run. This might be because muscle–tendon units crossing proximal joints are less equipped for energy storage and return compared with ankle plantar flexors and require greater muscle volume activation for a given force. To improve running performance, long-distance runners may benefit from an exercise-induced enhancement of ankle plantar flexor muscle–tendon unit capacities.
ICR142 Benchmarker: evaluating, optimising and benchmarking variant calling using the ICR142 NGS validation series
Authors: Ruark Elise , Holt Esty , Renwick Anthony , Münz Márton , Wakeling Matthew , Ellard Sian , Mahamdallie Shazia , Yost Shawn , Rahman Nazneen 
Published: August 2018

Evaluating, optimising and benchmarking of next generation sequencing (NGS) variant calling performance are essential requirements for clinical, commercial and academic NGS pipelines. Such assessments should be performed in a consistent, transparent and reproducible fashion, using independently, orthogonally generated data. Here we present ICR142 Benchmarker, a tool to generate outputs for assessing variant calling performance using the ICR142 NGS validation series, a dataset of exome sequence data from 142 samples together with Sanger sequence data at 704 sites. ICR142 Benchmarker provides summary and detailed information on the sensitivity, specificity and false detection rates of variant callers. ICR142 Benchmarker also automatically generates a single page report highlighting key performance metrics and how performance compares to widely-used open-source tools. We used ICR142 Benchmarker with VCF files outputted by GATK, OpEx and DeepVariant to create a benchmark for variant calling performance. This evaluation revealed pipeline-specific differences and shared challenges in variant calling, for example in detecting indels in short repeating sequence motifs. We next used ICR142 Benchmarker to perform regression testing with versions 0.5.2 and 0.6.1 of DeepVariant. This showed that v0.6.1 improves variant calling performance, but there was evidence of some minor changes in indel calling behaviour that may benefit from attention in future updates. The data also allowed us to evaluate filters to optimise DeepVariant calling, and we recommend using 30 as the QUAL threshold for base substitution calls when using DeepVariant v0.6.1. Finally, we used ICR142 Benchmarker with VCF files from two commercial variant calling providers to facilitate optimisation of their in-house pipelines and to provide transparent benchmarking of their performance. ICR142 Benchmarker consistently and transparently analyses variant calling performance based on the ICR142 NGS validation series, using the standard VCF input and outputting informative metrics to enable user understanding of pipeline performance. ICR142 Benchmarker is freely available at https://github.com/RahmanTeamDevelopment/ICR142_Benchmarker/releases.
A Conceptual Framework for Disruptive Innovation in Advising
Authors: Hamada Kay S. 
Published: August 2018

Institutions of higher education seek innovative opportunities to keep up with changing student needs. Accordingly, frameworks such as Christensen’s Disruptive Innovation theory may appear attractive on the surface to improve advising practices, but a deeper under-standing of context and objectives is imperative to recognizing the applicability of such frame-works to practice. By clarifying what Disruptive Innovation is, and is not (i.e., sustaining innovation), it has been argued that the theory has been misunderstood and misapplied (Christensen et al., “What is Disruptive Innovation?”). A closer look reveals that in addition to benefits, the Disruptive Innovation framework also poses a number of challenges to advising. This study sets out to (1) clarify the theoretical framework of Disruptive Innovation and explore the relationship between Disruptive Innovation and advising; (2) examine the extent to which Disruptive Innovation theory can be applied in advising, via a case study; and (3) discuss the implications for Disruptive Innovation in advising.
JUSTICE IN MANY ROOMS IN SHARIA BANKING DISPUTE RESOLUTION TO ACHIEVE JUSTICE
Authors: Triana Nita 
Published: August 2018

This paper examines the dispute resolution of Sharia Banking. The method is a non-doctrinal legal research using qualitative research and Socio Legal approach. Sharia banking cannot be separated from the problems between the banking and the Customer. This problem is calledproblematic financing. The resolution of problematic financing of sharia banks in litigation is now the absolute authority of the Religious Courts. The downside of litigation settlement usually takes a long time, the need for proof, the cost is quite expensive and the result is winningor lost. Therefore, the settlement of sharia banking is very rarely resolved through litigation. Alternative Dispute Resolution is a choice of dispute settlement chosen by Sharia Banking. The first stage isto carry out negotiation between all parties, namely Banking (lender) and The Customer (Debtor) in the form of warning and guidance. If it does not succeed, there will bedebt restructuration. The second step is mediation, in the form of consultation with third party as a mediator. The mediation determines the rescue process of debt by Banks when a debtor is still unable to return his debt, executed by the bank. According to Marc Galanter these various dispute resolutionsis called justice in many rooms. In Islamic Law it is known as Sulh (peace). However, to a large extent this non-litigation settlement is more satisfactory to both parties in resolving the dispute because it senses fairness and a win-win solution.
Gene therapy for PNP deficiency protocol
Authors: Vong Linda 
Published: August 2018

Purine nucleoside phosphorylase (PNP) is a key enzyme required for the degradation of purine nucleosides into uric acid or their salvage into nucleic acids. Patients who are deficient in PNP suffer from progressive T cell immunodeficiency, with increased susceptibility to infections, autoimmunity, and neurologic abnormalities. In the absence of successful treatment to restore immune function, these patients rarely survive to adulthood. Hematopoietic stem cell transplantation is the only known cure for PNP deficiency. Use of an HLA-matched donor is preferable as the outcome with alternative donors have been variable; however, this option is rarely available. Gene therapy represents a therapeutic option that bypasses the need for a donor, and thus associated complications. Although first generation γ-retroviral vectors have been successful in some immunodeficiencies, in others, evidence of insertional mutagenesis prompted a halt in their use. More recently, the introduction of safer lentiviral vectors holds promise in offering a viable option to treat immunodeficiency. Here, we present a clinical trial protocol utilizing self-inactivating lentiviral vectors to treat PNP deficiency. Patients will be evaluated up to 3 years post-transplantation to determine the safety of lentiviral-treated stem cell infusion, as well as the extent of immune reconstitution. Statement of novelty: This protocol describes the novel treatment of PNP deficiency using lentiviral-based gene therapy.
Mining Landforms: An Integrated Approach for Assessing the Geotourism and Geoeducational Potential
Authors: Kubalíková Lucie 
Published: August 2018

Abstract
Anthropogenic landforms (especially the mining landforms – quarries, pits, mines) have undoubtedly a great potential for the geotourism development. In addition, they are important from the geoconservation and geoeducation point of view as they allow to see the Earth-science features that would normally remain hidden (e.g., stratigraphic boundaries or soil profiles). However, the potential of these landforms in some case is not fully recognized and the sites themselves can even be endangered. The article presents guidelines for inventorying and assessment method for geotourism and geoeducational purposes of these specific landforms (respectively, the mining geosites and geomorphosites which are going to be used for geotourism and geoeducation) and gives an example from the area in which geotourism has not been fully developed yet (Červený kopec/Red Hill in Brno, Czech Republic).
Temperature and resource availability drive the seasonal abundance of Artibeus lituratus (Chiroptera: Phyllostomidae) in Atlantic Forest remnants of southeastern Brazil
Authors: de Souza Laurindo Rafael , Gregorin Renato 
Published: August 2018

Abstract
The great fruit-eating bat (Artibeus lituratus) is a large-sized bat in the New World family Phyllostomidae. It is widely distributed and sometimes very abundant in different Brazilian biomes, in natural and anthropic environments. Studies in the tropics have found evidence of a decrease in A. lituratus captures during the winter, a dry and cold season with low fruit availability, especially in higher latitudes. However, the causes for the decrease in captures are poorly understood. The objective of this study was to test the influence of temperature and fruit availability on capture rates of A. lituratus in a fragmented Atlantic Forest landscape. Results indicate that temperature is the main variable that explains the changes in the number of captures of A. lituratus throughout the year, and that fruit availability plays only an adjacent role. In addition, we highlight possible negative consequences of climate change on the survival of this species.