bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between V̇o2peak, cycle economy, and mitochondrial respiration in untrained/trained
Authors: Hunter Gary R. , Moellering Douglas R. , Windham Samuel T. , Mathis Shannon L. , Bamman Marcas M. , Fisher Gordon 
Published: September 2019

Aerobic capacity is negatively related to locomotion economy. The purpose of this paper is to determine what effect aerobic exercise training has on the relationship between net cycling oxygen uptake (inverse of economy) and aerobic capacity [peak oxygen uptake (V̇o2peak)], as well as what role mitochondrial coupled and uncoupled respiration may play in whole body aerobic capacity and cycling economy. Cycling net oxygen uptake and V̇o2peak were evaluated on 31 premenopausal women before exercise training (baseline) and after 8–16 wk of aerobic training. Muscle tissue was collected from 15 subjects at baseline and post-training. Mitochondrial respiration assays were performed using high-resolution respirometry. Pre- ( r = 0.46, P < 0.01) and postexercise training ( r = 0.62, P < 0.01) V̇o2peak and cycling net oxygen uptake were related. In addition, uncoupled and coupled fat respiration were related both at baseline ( r = 0.62, P < 0.01) and post-training ( r = 0.89, P < 01). Post-training coupled ( r = 0.74, P < 0.01) and uncoupled carbohydrate respiration ( r = 0.52, P < 05) were related to cycle net oxygen uptake. In addition, correlations between V̇o2peak and cycle net oxygen uptake persist both at baseline and after training, even after adjusting for submaximal cycle respiratory quotient (an index of fat oxidation). These results suggest that the negative relationship between locomotion economy and aerobic capacity is increased following exercise training. In addition, it is proposed that at least one of the primary factors influencing this relationship has its foundation within the mitochondria. Strong relationships between coupled and uncoupled respiration appear to be contributing factors for this relationship. NEW & NOTEWORTHY The negative relationship between cycle economy and aerobic capacity is increased following exercise training. The strong relationship between coupled and uncoupled respiration, especially after training, appears to be contributing to this negative relationship between aerobic capacity and cycling economy, suggesting that mitochondrial economy is not increased following aerobic exercise training. These results are suggestive that training programs designed to improve locomotion economy should focus on changing biomechanics.
Time-based pulmonary features from electrical impedance tomography demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease
Authors: Milne Stephen , Huvanandana Jacqueline , Nguyen Chinh , Duncan Joseph M. , Chapman David G. , Tonga Katrina O. , Zimmermann Sabine C. , Slattery Alexander , King Gregory G. , Thamrin Cindy 
Published: September 2019

Pulmonary electrical impedance tomography (EIT) is a functional imaging technique that allows real-time monitoring of ventilation distribution. Ventilation heterogeneity (VH) is a characteristic feature of chronic obstructive pulmonary disease (COPD) and has previously been quantified using features derived from tidal variations in the amplitude of the EIT signal. However, VH may be better described by time-based metrics, the measurement of which is made possible by the high temporal resolution of EIT. We aimed 1) to quantify VH using novel time-based EIT metrics and 2) to determine the physiological relevance of these metrics by exploring their relationships with complex lung mechanics measured by the forced oscillation technique (FOT). We performed FOT, spirometry, and tidal-breathing EIT measurements in 11 healthy controls and 9 volunteers with COPD. Through offline signal processing, we derived 3 features from the impedance-time ( Z- t) curve for each image pixel: 1) tE, mean expiratory time; 2) PHASE, mean time difference between pixel and global Z- t curves; and 3) AMP, mean amplitude of Z- t curve tidal variation. Distribution was quantified by the coefficient of variation (CV) and the heterogeneity index (HI). Both CV and HI of the tE and PHASE features were significantly increased in COPD compared with controls, and both related to spirometry and FOT resistance and reactance measurements. In contrast, distribution of the AMP feature showed no relationships with lung mechanics. These novel time-based EIT metrics of VH reflect complex lung mechanics in COPD and have the potential to allow real-time visualization of pulmonary physiology in spontaneously breathing subjects. NEW & NOTEWORTHY Pulmonary electrical impedance tomography (EIT) is a real-time imaging technique capable of monitoring ventilation with exquisite temporal resolution. We report novel, time-based EIT measurements that not only demonstrate ventilation heterogeneity in chronic obstructive pulmonary disease (COPD), but also reflect oscillatory lung mechanics. These EIT measurements are noninvasive, radiation-free, easy to obtain, and provide real-time visualization of the complex pathophysiology of COPD.
Modeling Cellular Response in Large-Scale Radiogenomic Databases to Advance Precision Radiotherapy
Authors: Manem Venkata SK. , Lambie Meghan , Smith Ian , Smirnov Petr , Kofia Victor , Freeman Mark , Koritzinsky Marianne , Abazeed Mohamed E. , Haibe-Kains Benjamin , Bratman Scott V. 
Published: September 2019

AbstractRadiotherapy is integral to the care of a majority of patients with cancer. Despite differences in tumor responses to radiation (radioresponse), dose prescriptions are not currently tailored to individual patients. Recent large-scale cancer cell line databases hold the promise of unravelling the complex molecular arrangements underlying cellular response to radiation, which is critical for novel predictive biomarker discovery. Here, we present RadioGx, a computational platform for integrative analyses of radioresponse using radiogenomic databases. We fit the dose–response data within RadioGx to the linear-quadratic model. The imputed survival across a range of dose levels (AUC) was a robust radioresponse indicator that correlated with biological processes known to underpin the cellular response to radiation. Using AUC as a metric for further investigations, we found that radiation sensitivity was significantly associated with disruptive mutations in genes related to nonhomologous end joining. Next, by simulating the effects of different oxygen levels, we identified putative genes that may influence radioresponse specifically under hypoxic conditions. Furthermore, using transcriptomic data, we found evidence for tissue-specific determinants of radioresponse, suggesting that tumor type could influence the validity of putative predictive biomarkers of radioresponse. Finally, integrating radioresponse with drug response data, we found that drug classes impacting the cytoskeleton, DNA replication, and mitosis display similar therapeutic effects to ionizing radiation on cancer cell lines. In summary, RadioGx provides a unique computational toolbox for hypothesis generation to advance preclinical research for radiation oncology and precision medicine.Significance:The RadioGx computational platform enables integrative analyses of cellular response to radiation with drug responses and genome-wide molecular data.
Urinary Leukotriene E4 and 2,3-Dinor Thromboxane B2 Are Biomarkers of Potential Harm in Short-Term Tobacco Switching Studies
Authors: Makena Patrudu , Liu Gang , Chen Peter , Yates Charles R. , Prasad G.L. 
Published: September 2019

Abstract

Background:
Modified risk tobacco products (MRTP) can reduce harm by decreasing exposure to combustion-related toxicants. In the absence of epidemiologic data, biomarkers of potential harm (BoPH) are useful to evaluate the harm-reducing potential of MRTPs. This study evaluated whether arachidonic acid (AA)-derived metabolites serve as short-term BoPH for predicting harm reduction in tobacco product–switching studies.

Methods:
We used 24-hour urine samples from participants in a series of short-term studies in which smokers switched from combustible to noncombustible tobacco products [oral smokeless tobacco products or electronic nicotine delivery system (ENDS)] or abstinence. Pre- and postswitching samples were analyzed by LC/MS-MS for alterations in select AA metabolites, including prostaglandins, isoprostanes, thromboxanes, and leukotrienes.

Results:
Switching to abstinence, dual use of combustible and noncombustible products, or exclusive use of noncombustible products resulted in reduced 2,3-d-TXB2 levels. Moreover, switching smokers to either abstinence or exclusive use of oral tobacco products resulted in reduced LTE4, but dual use of combustible and oral tobacco products or ENDS did not. A two-biomarker classification model comprising 2,3-d-TXB2 and LTE4 demonstrated the highest performance in distinguishing smokers switched to either abstinence or to ENDS and oral smokeless tobacco products.

Conclusions:
Urinary 2,3-d-TXB2 and LTE4 can discriminate between combustible tobacco users and combustible tobacco users switched to either abstinence or noncombustible products for 5 days.

Impact:
2,3-d-TXB2 and LTE4, which are linked to platelet activation and inflammation, represent BoPH in short-term tobacco product–switching studies. Thus, from a regulatory perspective, 2,3-d-TXB2 and LTE4 may aid in assessing the harm reduction potential of MRTPs.
Associations of Tobacco and Alcohol Use with Risk of Neuroendocrine Tumors of the Small Intestine in Utah
Authors: Curtin Karen , Cannon-Albright Lisa A. , VanDerslice James , Yu Zhe , Herget Kimberly A. , Thota Ramya , Neklason Deborah W. 
Published: September 2019

Abstract

Background:
Incidence of small-intestine neuroendocrine tumors (SINT) has been increasing in the United States over the past 40 years, with higher incidence in Utah than elsewhere. As information about how these tumors arise is limited, elucidating lifestyle factors associated with SINT in a statewide cohort could potentially identify those at risk to help mitigate their effects.

Methods:
Cases of SINT with a carcinoid histology (8240 or 8241) diagnosed in Utah from 1996 to 2014 with no prior history of cancer within 5 years (n = 433) were matched to population controls (1:10 ratio). Tobacco and alcohol exposures before case diagnosis were identified from International Classification of Diseases codes in statewide medical records and from self-reported data captured at patient encounters beginning in 1996. Multivariate logistic regression was used to estimate risk of SINT associated with tobacco and alcohol in cases compared with controls.

Results:
An increased risk of SINT was observed in tobacco-exposed individuals compared with unexposed [OR, 1.44; 95% confidence interval (CI), 1.11–1.86; P = 0.006]. Those who were exposed to alcohol exhibited an increased risk of SINT (OR, 1.62; 95% CI, 1.05–2.49; P = 0.03).

Conclusions:
This study supports tobacco and alcohol use as risk factors for SINT, independent of family history. However, low rates of smoking and alcohol use in Utah coupled with higher rates of SINT suggest other factors may contribute to development of these tumors.

Impact:
Although tobacco and alcohol modestly contribute to risk, our study suggests in addition to greater detection of tumors, other as-of-yet undefined exposures may drive rising SINT incidence.
Esophageal Thermal Exposure to Hot Beverages: A Comparison of Metrics to Discriminate Distinct Consumption Habits
Authors: Middleton Daniel R.S. , Xie Shuang-Hua , Bouaoun Liacine , Byrnes Graham , Song Guo-Hui , Schüz Joachim , Wei Wen-Qiang , McCormack Valerie A. 
Published: September 2019

Abstract

Background:
Hot beverage consumption is a probable risk factor for esophageal squamous cell carcinoma (ESCC). No standardized exposure assessment protocol exists.

Methods:
To compare how alternative metrics discriminate distinct drinking habits, we measured sip temperatures and sizes in an international group of hot beverage drinkers in France (n = 20) and hot porridge consumers (n = 52) in a high ESCC incidence region of China. Building on the knowledge that sip size and temperature affect intraesophageal liquid temperature (IELT), IELTs were predicted by modeling existing data, and compared with first sip temperature and, across all sips, mean temperature and sip-weighted mean temperature.

Results:
Two contrasting exposure characteristics were observed. Compared with the international group, Chinese porridge consumers took larger first sips [mean difference +17 g; 95% confidence interval (CI), 13.3–20.7] of hotter (+9.5°C; 95% CI, 6.2–12.7) liquid, and their mean sip size did not vary greatly across sips, but the former groups increased in size as temperature decreased. This resulted in higher predicted IELTs (mean 61°C vs. 42.4°C) and sip-weighted temperatures (76.9°C vs. 56°C) in Chinese porridge consumers, and compared with first sip and mean temperature, these two metrics separated the groups to a greater extent.

Conclusions:
Distinguishing thermal exposure characteristics between these groups was greatly enhanced by measuring sip sizes. Temperature at first sip alone is suboptimal for assessing human exposure to hot foods and beverages, and future studies should include sip size measurements in exposure assessment protocols.

Impact:
This study provides a logistically feasible framework for assessing human exposure to hot beverages.
Clinical Assessment of 5-Fluorouracil/Leucovorin, Nab-Paclitaxel, and Irinotecan (FOLFIRABRAX) in Untreated Patients with Gastrointestinal Cancer Using UGT1A1 Genotype–Guided Dosing
Authors: Joshi Smita S. , Catenacci Daniel V.T. , Karrison Theodore G. , Peterson Jaclyn D. , Zalupski Mark M. , Sehdev Amikar , Wade James , Sadiq Ahad , Picozzi Vincent J. , Amico Andrea , Marsh Robert , Kozloff Mark F. , Polite Blase N. , Kindler Hedy L. , Sharma Manish R. 
Published: September 2019

Abstract

Purpose:
5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with UGT1A1 genotype–guided dosing of irinotecan.

Patients and Methods:
Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. UGT1A1 *1/*1, *1/*28, and *28/*28 patients received initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2,400 mg/m2 over 46 hours, leucovorin 400 mg/m2, and nab-paclitaxel 125 mg/m2 were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure.

Results:
Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) *1/*1 patients, 1 of 19 (5%) *1/*28 patients, and 0 of 7 *28/*28 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks.

Conclusions:
FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Too few *28/*28 patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.
Bevacizumab Reduces Permeability and Concurrent Temozolomide Delivery in a Subset of Patients with Recurrent Glioblastoma
Authors: Gerstner Elizabeth R. , Emblem Kyrre E. , Chang Ken , Vakulenko-Lagun Bella , Yen Yi-Fen , Beers Andrew L. , Dietrich Jorg , Plotkin Scott R. , Catana Ciprian , Hooker Jacob M. , Duda Dan G. , Rosen Bruce , Kalpathy-Cramer Jayashree , Jain Rakesh K. , Batchelor Tracy 
Published: September 2019

Abstract

Purpose:
Targeting tumor blood vessels is an attractive therapy in glioblastoma (GBM), but the mechanism of action of these agents and how they modulate delivery of concomitant chemotherapy are not clear in humans. We sought to elucidate how bevacizumab modulates tumor vasculature and the impact those vascular changes have on drug delivery in patients with recurrent GBM.

Experimental Design:
Temozolomide was labeled with [11C], and serial PET-MRI scans were performed in patients with recurrent GBM treated with bevacizumab and daily temozolomide. PET-MRI scans were performed prior to the first bevacizumab dose, 1 day after the first dose, and prior to the third dose of bevacizumab. We calculated tumor volume, vascular permeability (Ktrans), perfusion (cerebral blood flow), and the standardized uptake values (SUV) of [11C] temozolomide within the tumor.

Results:
Twelve patients were enrolled, resulting in 23 evaluable scans. Within the entire contrast-enhancing tumor volume, both temozolomide uptake and vascular permeability decreased after initiation of bevacizumab in most patients, whereas change in perfusion was more variable. In subregions of the tumor where permeability was low and the blood–brain barrier not compromised, increased perfusion correlated with increased temozolomide uptake.

Conclusions:
Bevacizumab led to a decrease in permeability and concomitant delivery of temozolomide. However, in subregions of the tumor where permeability was low, increased perfusion improved delivery of temozolomide, suggesting that perfusion may modulate the delivery of chemotherapy in certain settings. These results support exploring whether lower doses of bevacizumab improve perfusion and concomitant drug delivery.
Report of five interesting avian species from Durgapur ecoregion, West Bengal, India by citizen science effort
Authors: Adhurya Sagar , Bhandary Shantanu 
Published: September 2019

This study aimed to report a few lesser known species from Durgapur ecoregion, West Bengal, India. In spite of the anthropogenic pressure, Durgapur supports a high avian diversity. So far, 257 avian species belonging to 59 families were recorded with a citizen science effort during a period of more than five years (2013–present). Out of these, five species discussed here, are either not recorded previously or have few records: Hume’s Lark and Graceful Prinia were recorded from riverine habitat; and Lesser Racket-tailed Drongo, White-rumped Shama, and Indian Blue-Robin were recorded from woodland habitat. More extensive exploration of this region with involvement of citizen scientists in this study will enrich our knowledge about bird diversity, their migration and distribution pattern in this region.
The distributional pattern of benthic macroinvertebrates in a spring-fed foothill tributary of the Ganga River, western Himalaya, India
Authors: Semwal Vijay Prakash , Mishra Asheesh Shivam 
Published: September 2019

Benthic macroinvertebrates play important ecosystem roles in the cycling and outflow of nutrients. The benthos transforms organic detritus from sedimentary storage into dissolved nutrients that can be mixed into overlying waters and used by rooted plants (macrophytes) and algae (phytoplankton) to enhance primary productivity. This study examined the distribution pattern of benthic macroinvertebrates in a lesser Himalayan foothill stream from the headwaters (2,200m) to mouth (375m). Five stations (S1 to S5) were established along the 43-km course of the stream. Samples were collected at bi-monthly intervals from January to December 2009. The total density of the benthic macroinvertebrate community increased with decreasing altitude and differed significantly among stations. Dominant orders were Diptera at S1 (Simulidae, 27%) & S5 (Chironomidae 24%), Trichoptera at S2 (Limnephilidae 16%) & S3 (Hydropsychidae 9.9%), and Ephemeroptera (Heptageniidae 9.2%) at S4. Principal component analysis revealed that the characteristic taxa were Simulidae at S1, Limnephildae at S2, Hydropsychiidae, Rhyacophilidae, Tipulidae, Perlodidae, Dryopidae & Notonectidae at S3, Heptageniidae at S4, and Chironomidae, Siphlonuridae, & Agrionidae at S5. Cluster analysis showed one large cluster comprising S1 and S2 as sub-groups with resemblance to S3-S4, and S5 as an outlier. The similarity between the stations S3-S4 was attributed to similar land-use pattern (agriculture) and stream order (II Order), while S1 and S2 were slightly similar due to partial similar forest type (oak forest at S1, pine-oak forest at S2) and stream order. At S5, however, the considerable change in forest type (mixed forest) land-use and stream order (III Order) caused S5 as an outlier in cluster. The variations in the abundant and characteristics taxon at different stations were attributed to change in substratum and land-use patterns.
C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes
Authors: Andersen Thomas , Ueland Thor , Ghukasyan Lakic Tatevik , Åkerblom Axel , Bertilsson Maria , Aukrust Pål , Michelsen Annika E. , James Stefan K. , Becker Richard C. , Storey Robert F. , Wallentin Lars , Siegbahn Agneta , Kontny Frederic ,   for the PLATO Investigators
Published: September 2019

Objective:
The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.

Approach and Results:

Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44–1.88),
P
<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05–1.45),
P
=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17–1.92],
P
=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.

Conclusions:
In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00391872