bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity
Authors: Dirksen Carsten , Graff Jesper , Fuglsang Stefan , Rehfeld Jens F. , Holst Jens J. , Madsen Jan L. 
Published: December 2018

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2(range of 47.9–69.0)] and 10 men without obesity [BMI of 24.6 kg/m2(range of 21.7–26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipidP = 0.046; GMETwaterP = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion.NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.
Integrated method for quantitative morphometry and oxygen transport modeling in striated muscle
Authors: Al-Shammari Abdullah A. , Kissane Roger W. P. , Holbek Simon , Mackey Abigail L. , Andersen Thomas R. , Gaffney Eamonn A. , Kjaer Michael , Egginton Stuart 
Published: December 2018

Identifying structural limitations in O2transport is primarily restricted by current methods employed to characterize the nature of physiological remodeling. Inadequate resolution or breadth of available data has impaired development of routine diagnostic protocols and effective therapeutic strategies. Understanding O2transport within striated muscle faces major challenges, most notably in quantifying how well individual fibers are supplied by the microcirculation, which has necessitated exploring tissue O2supply using theoretical modeling of diffusive exchange. With capillary domains identified as a suitable model for the description of local O2supply and requiring less computation than numerically calculating the trapping regions that are supplied by each capillary via biophysical transport models, we sought to design a high-throughput method for histological analysis. We present an integrated package that identifies optimal protocols for identification of important input elements, processing of digitized images with semiautomated routines, and incorporation of these data into a mathematical modeling framework with computed output visualized as the tissue partial pressure of O2(Po2) distribution across a biopsy sample. Worked examples are provided using muscle samples from experiments involving rats and humans.NEW & NOTEWORTHY Progress in quantitative morphometry and analytical modeling has tended to develop independently. Real diagnostic power lies in harnessing both disciplines within one user-friendly package. We present a semiautomated, high-throughput tool for determining muscle phenotype from biopsy material, which also provides anatomically relevant input to quantify tissue oxygenation, in a coherent package not previously available to nonspecialist investigators.
Effects of weight loss on dynamic hyperinflation in obese women asthmatics
Authors: Grandi Silva Aline , Duarte Freitas Patricia , Ferreira Palmira Gabriele , Stelmach Rafael , Carvalho-Pinto Regina Maria , Salge Joao Marcos , Arruda Martins Milton , Carvalho Celso R. F. 
Published: December 2018

Obese adults with asthma are more likely to develop dynamic hyperinflation (DH) and expiratory flow limitation (EFL) than nonobese asthmatics, and weight-loss seems to improve the breathing mechanics during exercise. However, studies evaluating the effect of weight loss on DH in obese adults with asthma have not been performed. We sought to evaluate the effect of a weight loss program on DH in obese adults with asthma. Forty-two asthma patients were enrolled in a weight loss program (diet, psychological support, and exercise) and were subsequently divided into two groups according to the percentage of weight loss: a ≥5% group ( n = 19) and a <5% group ( n = 23). Before and after the intervention, DH and EFL (constant load exercise), health-related quality of life (HRQoL), asthma control, quadriceps muscle strength and endurance, body composition, and lung function were assessed. Both groups exhibited a decrease of ≥10% in inspiratory capacity (DH) before intervention, and only the ≥5% group showed clinical improvement in DH compared with the <5% group postintervention (−9.1 ± 14.5% vs. −12.5 ± 13.5%, respectively). In addition, the ≥5% group displayed a significant delay in the onset of both DH and EFL and a clinically significant improvement in HRQoL and asthma control. Furthermore, a correlation was observed between reduced waist circumference and increased inspiratory capacity ( r = −0.45, P = 0.05) in the ≥5% group. In conclusion, a weight-loss of ≥5% of the body weight improves DH, which is associated with waist circumference in obese adults with asthma. In addition, the group with greater weight-loss showed a delayed onset of DH and EFL during exercise and improved asthma clinical control and HRQoL. NEW & NOTEWORTHY This is the first study to evaluate dynamic hyperinflation (DH) after a weight loss program in obese patients with asthma. Our results demonstrate that moderate weight loss can improve DH in obese patients with asthma that is associated with a decrease in abdominal fat. Moreover, a minimum of 5% in weight loss delays the onset of DH and expiratory flow limitation besides inducing a clinical improvement in asthma quality of life and clinical control.
Effect of net gas volume changes on alveolar and arterial gas partial pressures in the presence of ventilation-perfusion mismatch
Authors: Korman Ben , Dash Ranjan K. , Peyton Philip J. 
Published: December 2018

The second gas effect (SGE) occurs when nitrous oxide enhances the uptake of volatile anesthetics administered simultaneously. Recent work shows that the SGE is greater in blood than in the gas phase, that this is due to ventilation-perfusion mismatch, that as mismatch increases, the SGE increases in blood but is diminished in the gas phase, and that these effects persist well into the period of nitrous oxide maintenance anesthesia. These modifications of the SGE are most pronounced with the low soluble agents in current use. We investigate further the effect of net gas volume loss during nitrous oxide uptake on low concentrations of other gases present using partial pressure-solubility diagrams. The steady-state equations of gas exchange were solved assuming a log-normal distribution of ventilation-perfusion ratios using Lebesgue-Stieltjes integration. It was shown that under these conditions the classical partial pressure-solubility diagram must be modified, that for currently used volatile anesthetic agents the alveolar-arterial partial pressure difference is less than that predicted in the past, and that the alveolar-arterial partial pressure difference may even be reversed during uptake in the case of highly insoluble gases such as sulfur hexafluoride. Comparing this with the situation described previously for nitrogen in steady-state air breathing, we show that for nitrogen, the direction of the alveolar-arterial gradient is opposite to the direction of net gas volume movement. Although gas uptake with ventilation-perfusion inequality exceeding that when matching is optimal is shown to be possible, it is less likely than alveolar-arterial partial pressure reversal. NEW & NOTEWORTHY Net uptake of gases administered with nitrous oxide may proceed against an alveolar-arterial partial pressure gradient. The alveolar-arterial gradient for nitrogen in the steady-state breathing air depends not only on the existence of a distribution of ventilation-perfusion ratios in the lung but also on the presence of a net change in gas volume and is opposite in direction to the direction of net gas volume uptake.
The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes
Authors: Ulrich Cornelia M. , Gigic Biljana , Böhm Jürgen , Ose Jennifer , Viskochil Richard , Schneider Martin , Colditz Graham A. , Figueiredo Jane C. , Grady William M. , Li Christopher I. , Shibata David , Siegel Erin M. , Toriola Adetunji T. , Ulrich Alexis 
Published: December 2018

Abstract

Background:
Colorectal cancer is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether postdiagnosis diet and lifestyle can affect well-being and clinical outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with short-term and long-term patient-reported and clinical outcomes among patients with colorectal cancer.
Methods/Results: ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Germany. As of April 2018, we have recruited &gt;2,000 patients across all sites. Our projected enrollment is &gt;4,000 multiethnic patients with colorectal cancer. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes.

Conclusions:
ColoCare is a consortium for the investigation of multilevel factors relevant to colorectal cancer survivorship.

Impact:
The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on colorectal cancer.
The Secretome Engages STAT3 to Favor a Cytokine-rich Microenvironment in Mediating Acquired Resistance to FGFR Inhibitors
Authors: Wang Xinyi , Ai Jing , Liu Hongyan , Peng Xia , Chen Hui , Chen Yi , Su Yi , Shen Aijun , Huang Xun , Ding Jian , Geng Meiyu 
Published: December 2018

Abstract
Acquired resistance severely hinders the application of small-molecule inhibitors. Our understanding of acquired resistance related to FGFRs is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors (FGFRi) and investigated the potential mechanisms underlying acquired resistance. We discovered that reprogramming of the secretome is closely associated with acquired resistance to FGFRi. The secretome drives acquired resistance by activating the transcription factor STAT3 via its cognate receptors. Moreover, macrophages and fibroblasts could interact with cancer cells to enhance acquired resistance by promoting exaggerated and dynamic cytokine secretion, as well as STAT3 activation. We also found that Hsp90 and HDAC inhibitors could substantially and simultaneously suppress the proliferation of resistant cells, the secretion of multiple cytokines, and the activation of STAT3. Our study offers translational insights concerning the poor efficacy observed in patients with macrophage- and fibroblast-rich lung cancers and breast tumors after treatment with FGFRi in clinical trials.
KDM5B Promotes Drug Resistance by Regulating Melanoma-Propagating Cell Subpopulations
Authors: Liu Xiaoni , Zhang Shang-Min , McGeary Meaghan K. , Krykbaeva Irina , Lai Ling , Jansen Daniel J. , Kales Stephen C. , Simeonov Anton , Hall Matthew D. , Kelly Daniel P. , Bosenberg Marcus W. , Yan Qin 
Published: December 2018

Abstract
Tumor heterogeneity is a major challenge for cancer treatment, especially due to the presence of various subpopulations with stem cell or progenitor cell properties. In mouse melanomas, both CD34+p75− (CD34+) and CD34−p75− (CD34−) tumor subpopulations were characterized as melanoma-propagating cells (MPC) that exhibit some of those key features. However, these two subpopulations differ from each other in tumorigenic potential, ability to recapitulate heterogeneity, and chemoresistance. In this study, we demonstrate that CD34+ and CD34− subpopulations carrying the BRAFV600E mutation confer differential sensitivity to targeted BRAF inhibition. Through elevated KDM5B expression, melanoma cells shift toward a more drug-tolerant, CD34− state upon exposure to BRAF inhibitor or combined BRAF inhibitor and MEK inhibitor treatment. KDM5B loss or inhibition shifts melanoma cells to the more BRAF inhibitor–sensitive CD34+ state. These results support that KDM5B is a critical epigenetic regulator that governs the transition of key MPC subpopulations with distinct drug sensitivity. This study also emphasizes the importance of continuing to advance our understanding of intratumor heterogeneity and ultimately develop novel therapeutics by altering the heterogeneous characteristics of melanoma.
Genome-Wide Sequencing of Cell-Free DNA Identifies Copy-Number Alterations That Can Be Used for Monitoring Response to Immunotherapy in Cancer Patients
Authors: Jensen Taylor J. , Goodman Aaron M. , Kato Shumei , Ellison Christopher K. , Daniels Gregory A. , Kim Lisa , Nakashe Prachi , McCarthy Erin , Mazloom Amin R. , McLennan Graham , Grosu Daniel S. , Ehrich Mathias , Kurzrock Razelle 
Published: December 2018

Abstract
Inhibitors of the PD-1/PD-L1/CTLA-4 immune checkpoint pathway have revolutionized cancer treatment. Indeed, some patients with advanced, refractory malignancies achieve durable responses; however, only a subset of patients benefit, necessitating new biomarkers to predict outcome. Interrogating cell-free DNA (cfDNA) isolated from plasma (liquid biopsy) provides a promising method for monitoring response. We describe the use of low-coverage, genome-wide sequencing of cfDNA, validated extensively for noninvasive prenatal testing, to detect tumor-specific copy-number alterations, and the development of a new metric—the genome instability number (GIN)—to monitor response to these drugs. We demonstrate how the GIN can be used to discriminate clinical response from progression, differentiate progression from pseudoprogression, and identify hyperprogressive disease. Finally, we provide evidence for delayed kinetics in responses to checkpoint inhibitors relative to molecularly targeted therapies. Overall, these data demonstrate a proof of concept for using this method for monitoring treatment outcome in patients with cancer receiving immunotherapy.
Abstract P328: Effect of Sitagliptin on the Hemodynamic and Metabolic Response to a Mixed Meal in Individuals With Type 2 Diabetes and Hypertension
Authors: Wilson Jessica R , Kerman Scott J , Nian Hui , Hubers Scott , Brown Nancy J 
Published: December 2018

Dipeptidyl peptidase IV (DPP4) inhibitors such as sitagliptin are anti-diabetes drugs that may also have cardiovascular effects. We tested the hypothesis that there is an interactive effect between sitagliptin and angiotensin-converting enzyme (ACE) inhibition on blood pressure (SBP, DBP, MAP) and heart rate (HR) after a meal. We enrolled 52 type 2 diabetics (T2DM) with hypertension. The mean age was 56.1±10.2 years. 58.5% were men, 28.3% were black and 67.9% were white. Individuals were randomized to one of three BP agents: ramipril 10mg/d, valsartan 320mg/d [a renin-angiotensin-aldosterone system (RAAS) inhibiting drug without enzyme activity], and amlodipine 10mg/d (a RAAS-independent control) for 15 weeks. On the 5
th
, 10
th
, and 15
th
week of anti-hypertensive therapy each participant underwent one-week crossover treatment with sitagliptin 100 mg/d + placebo, placebo + placebo, and sitagliptin + aprepitant 80 mg/d (a substance P receptor blocker, as DPP4 and ACE degrade substance P). On the last day of each treatment, participants were given a mixed meal (712 calories: 45% from fat, 33% carbohydrate, 22% protein).

There was no difference in pre-prandial BP among the three crossover treatments. Following the meal, SBP (p=0.002) and MAP (p<0.001) were significantly decreased during either DPP4 inhibitor crossover treatment compared to placebo. In particular, in patients treated with an ACE inhibitor, post-prandial SBP (0.015) and MAP (p=0.021) were lower during DPP4 inhibition. This was true after controlling for significant effects of race (p=0.002) and gender (p=0.0007). Post-prandial HR was not affected by DPP4 inhibition during ACE inhibition. The effect of DPP4 inhibition on fasting glucose but not on postprandial glucose differed among anti-hypertensive treatment groups. DPP4 inhibition decreased the formation of PYY3-36 from PYY following the meal.
There is an interactive effect between DPP4 inhibition and anti-hypertensive therapy on post-prandial BP and metabolic parameters.
Risk of Death Following Application of Paclitaxel‐Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Katsanos Konstantinos , Spiliopoulos Stavros , Kitrou Panagiotis , Krokidis Miltiadis , Karnabatidis Dimitrios 
Published: December 2018

Background

Several randomized controlled trials (
RCT
s) have already shown that paclitaxel‐coated balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularization after lower extremity interventions.

Methods and Results

A systematic review and meta‐analysis of
RCT
s investigating paclitaxel‐coated devices in the femoral and/or popliteal arteries was performed. The primary safety measure was all‐cause patient death. Risk ratios and risk differences were pooled with a random effects model. In all, 28
RCT
s with 4663 patients (89% intermittent claudication) were analyzed. All‐cause patient death at 1 year (28
RCT
s with 4432 cases) was similar between paclitaxel‐coated devices and control arms (2.3% versus 2.3% crude risk of death; risk ratio, 1.08; 95% CI, 0.72–1.61). All‐cause death at 2 years (12
RCT
s with 2316 cases) was significantly increased in the case of paclitaxel versus control (7.2% versus 3.8% crude risk of death; risk ratio, 1.68; 95%
CI,
1.15–2.47; —number‐needed‐to‐harm, 29 patients [95%
CI
, 19–59]). All‐cause death up to 5 years (3
RCT
s with 863 cases) increased further in the case of paclitaxel (14.7% versus 8.1% crude risk of death; risk ratio, 1.93; 95%
CI
, 1.27–2.93; —number‐needed‐to‐harm, 14 patients [95%
CI
, 9–32]). Meta‐regression showed a significant relationship between exposure to paclitaxel (dose‐time product) and absolute risk of death (0.4±0.1% excess risk of death per paclitaxel mg‐year;
P
<0.001). Trial sequential analysis excluded false‐positive findings with 99% certainty (2‐sided α, 1.0%).

Conclusions
There is increased risk of death following application of paclitaxel‐coated balloons and stents in the femoropopliteal artery of the lower limbs. Further investigations are urgently warranted.

Clinical Trial Registration

URL
:
www.crd.york.ac.uk/PROSPERO
. Unique identifier:
CRD
42018099447.
Is the reported increase in young female hospital-treated intentional self-harm real or artefactual?
Authors: McGill Katie , Hiles Sarah A , Handley Tonelle E , Page Andrew , Lewin Terry J , Whyte Ian , Carter Gregory L 
Published: December 2018

Background: The Australian Institute of Health and Welfare has reported an increased rate of hospital-treated intentional self-harm in young females (2000–2012) in Australia. These reported increases arise from institutional data that are acknowledged to underestimate the true rate, although the degree of underestimation is not known. Objective: To consider whether the reported increase in young females’ hospital-treated intentional self-harm is real or artefactual and specify the degree of institutional underestimation. Methods: Averages for age- and gender-standardised event rates for hospital-treated intentional self-harm (national: Australian Institute of Health and Welfare; state: New South Wales Ministry of Health) were compared with sentinel hospital event rates for intentional self-poisoning (Hunter Area Toxicology Service, Calvary Mater Newcastle) in young people (15–24 years) for the period 2000–2012. A time series analysis of the event rates for the sentinel hospital was conducted. Results: The sentinel hospital event rates for young females of 444 per 100,000 were higher than the state (378 per 100,000) and national (331 per 100,000) rates. There was little difference in young male event rates – sentinel unit: 166; state: 166 and national: 153 per 100,000. The sentinel hospital rates showed no change over time for either gender. Conclusion: There was no indication from the sentinel unit data of any increase in rates of intentional self-poisoning for young females. The sentinel and state rates were higher than the national rates, demonstrating the possible magnitude of underestimation of the national data. The reported increases in national rates of hospital-treated self-harm among young females might be due to artefactual factors, such as changes in clinical practice (greater proportion admitted), improved administrative coding of suicidal behaviours or possibly increased hospital presentations of community self-injury cases, but not intentional self-poisoning. A national system of sentinel units is needed for the accurate and timely monitoring of all hospital-treated self-harm.
Marketing's Job for the 1960s
Authors: Keener J. W. 
Published: December 2018

Vast growth of consumer markets in the 1960s is now clearly seen, but what special risks and opportunities face the marketing man? How fast will he have to run just to stay even with his competition? And what new competitive forces will he meet? Mr. Keener, President of The B. F. Goodrich Company, suggests that complacent expectation of a steadily expanding economy is not enough. Profitable operation during the next decade will depend on how a company meets a specific list of challenges, and the author discusses these challenges.