bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detrital-zircon records of Cenomanian, Paleocene, and Oligocene Gulf of Mexico drainage integration and sediment routing: Implications for scales of basin-floor fans
Authors: Blum Michael D. , Milliken Kristy T. , Pecha Mark A. , Snedden John W. , Frederick Bruce C. , Galloway William E. 
Published: October 2017

AbstractThis paper uses detrital zircon (DZ) provenance and geochronological data to reconstruct paleodrainage areas and lengths for sediment-routing systems that fed the Cenomanian Tuscaloosa-Woodbine, Paleocene Wilcox, and Oligocene Vicksburg-Frio clastic wedges of the northern Gulf of Mexico (GoM) margin. During the Cenomanian, an ancestral Tennessee-Alabama River system with a distinctive Appalachian DZ signature was the largest system contributing water and sediment to the GoM, with a series of smaller systems draining the Ouachita Mountains and discharging sediment to the western GoM. By early Paleocene Wilcox deposition, drainage of the southern half of North America had reorganized such that GoM contributing areas stretched from the Western Cordillera to the Appalachians, and sediment was delivered to a primary depocenter in the northwestern GoM, the Rockdale depocenter fed by a paleo–Brazos-Colorado River system, as well as to the paleo–Mississippi River in southern Louisiana. By the Oligocene, the western drainage divide for the GoM had migrated east to the Laramide Rockies, with much of the Rockies now draining through the paleo–Red River and paleo–Arkansas River systems to join the paleo–Mississippi River in the southern Mississippi embayment. The paleo–Tennessee River had diverted to the north toward its present-day junction with the Ohio River by this time, thus becoming a tributary to the paleo-Mississippi within the northern Mississippi embayment. Hence, the paleo-Mississippi was the largest Oligocene system of the northern GoM margin.Drainage basin organization has had a profound impact on sediment delivery to the northern GoM margin. We use paleodrainage reconstructions to predict scales of associated basin-floor fans and test our predictions against measurements made from an extensive GoM database. We predict large fan systems for the Cenomanian paleo–Tennessee-Alabama, and especially for the two major depocenters of the early Paleocene paleo–Brazos-Colorado and late Paleocene–earliest Eocene paleo-Mississippi systems, and for the Oligocene paleo-Mississippi. With the notable exception of the Oligocene, measured fans reside within the range of our predictions, indicating that this approach can be exported to other basins that are less data rich.
Simultaneous K-ras activation and Keap1 deletion cause atrophy of pancreatic parenchyma
Authors: Hamada Shin , Shimosegawa Tooru , Taguchi Keiko , Nabeshima Tatsuhide , Yamamoto Masayuki , Masamune Atsushi 
Published: October 2017

The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system has a wide variety of effects in addition to the oxidative stress response, such as growth promotion and chemoresistance of cancer cells. Nrf2 is constitutively activated in most cancer cells. However, the activation of Nrf2 together with oncogenic mutations does not always result in cancer promotion. K-rasLSL-G12D/+:: p53LSL-R172H/+:: Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer that specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre. We here generated Pdx-1-Cre::K-rasLSL-G12D/+:: Keap1fl/fl (KC::Keap1) and KPC:: Keap1fl/fl (KPC::Keap1) mice in which Nrf2 is constitutively activated by Keap1 deletion. KC::Keap1 and KPC::Keap1 mice started to die or showed obvious weakness at approximately around 40 days after birth. Histological examination revealed that KC::Keap1 and KPC::Keap1 mice did not develop pancreatic cancer but, instead, progressive atrophy of the pancreatic parenchyma. In these mice, amylase-positive acinar cells as well as insulin- and glucagon-positive islet cells were decreased and surrounded by fibrotic tissues. KC::Keap1 and KPC::Keap1 mice presented lower body weight and glucose levels than C::Keap1 mice, presumably resulting from pancreatic exocrine insufficiency. Histological changes were not obvious in C::Keap1 and PC::Keap1 mice. The presence of the p53 mutation did not affect the phenotypes in KC::Keap1 mice. Heterologous or homologous Nrf2 deletion ( Nrf2+/− or Nrf2−/−) rescued the pancreatic phenotypes, weight loss, and hypoglycemia in KC::Keap1 mice, suggesting that Nrf2 is a major downstream target of Keap1. In conclusion, simultaneous K-ras activation and Keap1 deletion caused progressive atrophy of the pancreatic parenchyma in mice. NEW & NOTEWORTHY Aberrant activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system usually promotes carcinogenesis, and we assumed that simultaneous activation of K-ras and Nrf2 might promote pancreatic carcinogenesis. Conditional expression of mutant K-ras and Keap1 deletion did not result in pancreatic cancer development. Instead, these mice developed progressive loss of pancreatic parenchyma, accompanied by body weight loss and hypoglycemia, presumably because of pancreatic exocrine insufficiency. Nrf2 activation by Keap1 deletion concomitant with K-ras activation cause pancreatic atrophy.
Bubble and macroaggregate methods differ in detection of blood flow through intrapulmonary arteriovenous anastomoses in upright and supine hypoxia in humans
Authors: Duke Joseph W. , Elliott Jonathan E. , Laurie Steven S. , Voelkel Thomas , Gladstone Igor M. , Fish Mathews B. , Lovering Andrew T. 
Published: October 2017

Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) increases in healthy humans breathing hypoxic gas and is potentially dependent on body position. Previous work in subjects breathing room air has shown an effect of body position when Q̇IPAVA is detected with transthoracic saline contrast echocardiography (TTSCE). However, the potential effect of body position on Q̇IPAVA has not been investigated when subjects are breathing hypoxic gas or with a technique capable of quantifying Q̇IPAVA. Thus the purpose of this study was to quantify the effect of body position on Q̇IPAVA when breathing normoxic and hypoxic gas at rest. We studied Q̇IPAVA with TTSCE and quantified Q̇IPAVA with filtered technetium-99m-labeled macroaggregates of albumin (99mTc-MAA) in seven healthy men breathing normoxic and hypoxic (12% O2) gas at rest while supine and upright. On the basis of previous work using TTSCE, we hypothesized that the quantified Q̇IPAVA would be greatest with hypoxia in the supine position. We found that Q̇IPAVA quantified with 99mTc-MAA significantly increased while subjects breathed hypoxic gas in both supine and upright body positions (ΔQ̇IPAVA = 0.7 ± 0.4 vs. 2.5 ± 1.1% of cardiac output, respectively). Q̇IPAVA detected with TTSCE increased from normoxia in supine hypoxia but not in upright hypoxia (median hypoxia bubble score of 2 vs. 0, respectively). Surprisingly, Q̇IPAVA magnitude was greatest in upright hypoxia, when Q̇IPAVA was undetectable with TTSCE. These findings suggest that the relationship between TTSCE and 99mTc-MAA is more complex than previously appreciated, perhaps because of the different physical properties of bubbles and MAA in solution. NEW & NOTEWORTHY Using saline contrast bubbles and radiolabeled macroaggregrates (MAA), we detected and quantified, respectively, hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) in supine and upright body positions in healthy men. Upright hypoxia resulted in the largest magnitude of Q̇IPAVA quantified with MAA but the lowest Q̇IPAVA detected with saline contrast bubbles. These surprising results suggest that the differences in physical properties between saline contrast bubbles and MAA in blood may affect their behavior in vivo.
Local Adjuvant Treatment with Low-Dose CpG-B Offers Durable Protection against Disease Recurrence in Clinical Stage I–II Melanoma: Data from Two Randomized Phase II Trials
Authors: Koster Bas D. , van den Hout Mari F.C.M. , Sluijter Berbel J.R. , Molenkamp Barbara G. , Vuylsteke Ronald J.C.L.M. , Baars Arnold , van Leeuwen Paul A.M. , Scheper Rik J. , Petrousjka van den Tol M. , van den Eertwegh Alfons J.M. , de Gruijl Tanja D. 
Published: October 2017

Abstract
Purpose: Although risk of recurrence after surgical removal of clinical stage I–II melanoma is considerable, there is no adjuvant therapy with proven efficacy. Here, we provide clinical evidence that a local conditioning regimen, aimed at immunologic arming of the tumor-draining lymph nodes, may provide durable protection against disease recurrence (median follow-up, 88.8 months).
Experimental Design: In two randomized phase II trials, patients, diagnosed with stage I–II melanoma after excision of the primary tumor, received local injections at the primary tumor excision site within 7 days preceding re-excision and sentinel lymph node (SLN) biopsy of either a saline placebo (n = 22) or low-dose CpG type B (CpG-B) with (n = 9) or without (n = 21) low-dose GM-CSF.
Results: CpG-B treatment was shown to be safe, to boost locoregional and systemic immunity, to be associated with lower rates of tumor-involved SLN (10% vs. 36% in controls, P = 0.04), and, at a median follow-up of 88.8 months, to profoundly improve recurrence-free survival (P = 0.008), even for patients with histologically confirmed (i.e., pathologic) stage I–II disease (P = 0.02).
Conclusions: Potentially offering durable protection, local low-dose CpG-B administration in early-stage melanoma provides an adjuvant treatment option for a large group of patients currently going untreated despite being at considerable risk for disease recurrence. Once validated in a larger randomized phase III trial, this nontoxic immunopotentiating regimen may prove clinically transformative. Clin Cancer Res; 23(19); 5679–86. ©2017 AACR.
Christian Migrant Communities
Authors: Drønen Tomas Sundnes 
Published: October 2017

AbstractThe growing literature on religion and migration offers a wide range of terminologies in order to describe different aspects of the migratory trajectory. The article analyses how the three terms “transnational”, “transcultural”, and “translocal” are applied by different scholars in order to describe how religion influences and frames the experiences of those who leave their homes behind. It is further argued that discourse analysis can be a helpful methodological and analytical approach towards the field under study in order to engage with the rich variety of sources which might help us develop a yet more finely tuned analysis of the new religious communities. With the object of exemplifying how discourse analysis can be applied in future studies, the article gives examples from three different contexts where religious practices face change due to the migratory situation. The first example proposes studies of the “simultaneity aspect” in transnational studies among Nigerian migrants in Europe. The second example highlights how translocal aspects influence the study of ethnicity among migrants to cities in northern Cameroon, and the third example focuses on transcultural aspects of historical conversion narratives.
Elucidating the Role of Anthropogenic Aerosols in Arctic Sea Ice Variations
Authors: Wang Yuan , Jiang Jonathan H. , Su Hui , Choi Yong-Sang , Huang Lei , Guo Jianping , Yung Yuk L. 
Published: October 2017

AbstractObservations show that the Arctic sea ice cover has been shrinking at an unprecedented rate since the 1970s. Even though the accumulation of greenhouse gases in the atmosphere has been closely linked with the loss of Arctic sea ice, the role of atmospheric aerosols in past and future Arctic climate change remains elusive. Using a state-of-the-art fully coupled climate model, the authors assess the equilibrium responses of the Arctic sea ice to the different aerosol emission scenarios and investigate the pathways by which aerosols impose their influence in the Arctic. These sensitivity experiments show that the impacts of aerosol perturbations on the pace of sea ice melt effectively modulate the ocean circulation and atmospheric feedbacks. Because of the contrasting evolutions of particulate pollution in the developed and developing countries since the 1970s, the opposite aerosol forcings from different midlatitude regions are nearly canceled out in the Arctic during the boreal summer, resulting in a muted aerosol effect on the recent sea ice changes. Consequently, the greenhouse forcing alone can largely explain the observed Arctic sea ice loss up to the present. In the next few decades, the projected alleviation of particulate pollution in the Northern Hemisphere can contribute up to 20% of the total Arctic sea ice loss and 0.7°C surface warming over the Arctic. The authors’ model simulations further show that aerosol microphysical effects on the Arctic clouds are the major component in the total aerosol radiative forcing over the Arctic. Compared to the aerosol-induced energy imbalance in lower latitudes outside the Arctic, the local radiative forcing by aerosol variations within the Arctic, due to either local emissions or long-range transports, is more efficient in determining the sea ice changes and Arctic climate change.
Quality Control of Surface Wind Observations in Northeastern North America. Part I: Data Management Issues
Authors: Lucio-Eceiza Etor E. , González-Rouco J. Fidel , Navarro Jorge , Beltrami Hugo 
Published: October 2017

AbstractA quality control (QC) process has been developed and implemented on an observational database of surface wind speed and direction in northeastern North America. The database combines data from 526 land stations and buoys spread across eastern Canada and five adjacent northeastern U.S. states. It combines the observations of three different institutions spanning from 1953 to 2010. The quality of these initial data varies among source institutions. The current QC process is divided into two parts. Part I, described herein, is focused on issues related to data management: issues stemming from data transcription and collection; differences in measurement units and recording times; detection of sequences of duplicated data; unification of calm and true north criteria for wind direction; and detection of physically unrealistic data measurements. As a result, around ~0.1% of wind speed and wind direction records have been identified as erroneous and deleted. The most widespread error type is related to duplications within the same station, but the error type that entails more erroneous data belongs to duplications among different sites. Additionally, the process of data compilation and standardization has had an impact on more than 90% of the records. A companion paper (Part II) deals with a group of errors that are conceptually different, and is focused on detecting measurement errors that relate to temporal consistency and biases in wind speed and direction.
Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction, Prior or Concurrent Malignancy, and Comorbidities Working Group
Authors: Lichtman Stuart M. , Harvey R. Donald , Damiette Smit Marie-Anne , Rahman Atiqur , Thompson Michael A. , Roach Nancy , Schenkel Caroline , Bruinooge Suanna S. , Cortazar Patricia , Walker Dana , Fehrenbacher Louis 
Published: October 2017

Purpose Patients with organ dysfunction, prior or concurrent malignancies, and comorbidities are often excluded from clinical trials. Excluding patients on the basis of these factors results in clinical trial participants who are healthier and younger than the overall population of patients with cancer. Methods ASCO and Friends of Cancer Research established a multidisciplinary working group that included experts in trial design and conduct to examine how eligibility criteria could be more inclusive. The group analyzed current eligibility criteria; conducted original data analysis; considered safety concerns, potential benefits, research, and potential hurdles of this approach through discussion; and reached consensus on recommendations regarding updated eligibility criteria that prioritize inclusiveness without compromising patient safety. Results If renal toxicity and clearance are not of direct treatment-related concern, then patients with lower creatinine clearance values of > 30 mL/min should be included in trials. Inclusion of patients with mild to moderate hepatic dysfunction may be possible when the totality of the available nonclinical and clinical data indicates that inclusion is safe. Ejection fraction values should be used with investigator assessment of a patient’s risk for heart failure to determine eligibility. Patients with laboratory parameters out of normal range as a result of hematologic disease should be included in trials. Measures of patient functional status should be included in trials to better assess fit versus frail patients. Conclusion Expanding inclusion of these patients will increase the number and diversity of patients in clinical trials and result in a more appropriate population of patients.
Modernizing Clinical Trial Eligibility: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Minimum Age Working Group
Authors: Gore Lia , Ivy S. Percy , Balis Frank M. , Rubin Eric , Thornton Katherine , Donoghue Martha , Roberts Samantha , Bruinooge Suanna , Ersek Jennifer , Goodman Nancy , Schenkel Caroline , Reaman Gregory 
Published: October 2017

Purpose Children have historically been excluded from first-in-human studies of promising new cancer drugs and later phase adult clinical trials. Delays in evaluation may result in off-label use without dosing information as the only access to new drugs. A multistakeholder workshop was convened in May 2016 by ASCO and Friends of Cancer Research to identify opportunities for when it would be scientifically appropriate to expand trial eligibility to include children younger than age 18 years in first-in-human and other adult cancer clinical trials. Methods This group convened experts from academia, government, and industry to review barriers to enrolling children and adolescents in oncology clinical trials. We evaluated the historical context, published literature, regulatory considerations, and myriad risks and benefits associated with lowering the age of enrollment on oncology clinical trials. Results We conclude that many of the historical concerns about including children early in oncology clinical trials do not apply in the current scientific and clinical environment of pediatric oncology and drug development; we provide specific recommendations for how the inclusion of children in early-phase investigational cancer drug trials might be accomplished. Automatic inclusion of pediatric patients is appropriate in early-phase trials that assess dose, safety, and pharmacokinetics in a variety of tumor types and later phase trials that assess efficacy in a specific disease that spans adult and pediatric populations. Conclusion Including children in appropriately designed adult clinical oncology trials is feasible and can be done in a way that enhances their access to these agents without compromising safety or development strategies.
Could night-guards be used as a simple method to detect leached-elements from dental restorations intra-orally? A study on amalgam restorations
Authors: Abdelraouf Rasha Mohamed 
Published: October 2017

Background: Detection of leached-elements from dental restorations intra-orally has been a subject of prime importance in dental research. However, this is challenging as most of the present techniques have some limitations. In this study, a new simple method was proposed via using night-guards. Thus, the aim of the study was to verify if night-guards could detect leached-elements from restorations as dental amalgam. Methods: Ten upper custom-made night-guards were fabricated for patients suffering from bruxism, who had amalgam-restorations in their upper molars. The night-guards were delivered to the patients and they were instructed to wear the night-guards during when they were asleep. After six months, the night-guards were taken from the patients to be analyzed. A new unused night-guard was fabricated from the same material to be used as a control. In the used night-guards, two areas were studied: the fitting surfaces contacting the amalgam restorations and the fitting surfaces not contacting amalgam restorations. Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Analysis (EDXA) were used to examine the structural and elemental changes in the night-guards. Results: SEM of the unused night-guard revealed a homogenous structure, and the composition was carbon and oxygen, as shown using EDXA (C=88.9wt% and O=11.1wt%). By contrast, the fitting surfaces of the night-guards contacting amalgam restorations showed numerous lustrous particles. Elemental analysis of these areas showed the presence of mercury and sulfur, in addition to carbon and oxygen (Hg=21.2wt%, S=2.5wt%, C=67.1wt% and O=9.2wt%). The night-guards’ fitting surfaces not contacting amalgam restorations showed slight cracking, and the composition was carbon and oxygen (C=88.3wt% and O=11.7 wt%). Conclusions: Analyzing fitting surfaces of night-guards contacting dental restorations, such as amalgam, could aid in understanding the nature of leached-elements from these restorations intra-orally. However, further studies about its application upon dental-restorations other than amalgam are recommended.
Genetic diversity and multiplicity of Plasmodium falciparum merozoite surface protein 2 in field isolates from Sudan
Authors: Mustafa Shaza O. , Abdel Hamid Muzamil M. , Aboud Mariam A. , Amin Mutaz , Muneer Mohamed S. , Yasin Kyakonye , Mahgoub Nouh S. , El Bagir Nabiela M. 
Published: October 2017

Background: Malaria is a major health problem, with over one third of worldwide populations currently at risk. Determining the genetic diversity of plasmodium parasites is essential for assessing the efficacy of antimalarial drugs and for future vaccine development. This study investigated the genetic diversity of P. falciparum merozoite surface protein 2 (MSP2), and multiplicity of infection (MOI) in different geographic regions in Sudan. Methods: A total of 271 patients with uncomplicated malaria were recruited from four ecological sites during malaria transmission season, 2011-2013. P. falciparum was confirmed using species specific primers targeting the rDNA gene. All P. falciparum positive samples were genotyped for the major MSP2 allelic families (IC1/3D7 and FC27 MSP2 allele) using nested PCR. Multiplicity of infection and allele frequencies were determined. Results: A total of 241 samples (88.9%) were confirmed positive for P. falciparum. The number of different MSP2 alleles were 14, 15, 13 and 12 in Khartoum, Gezira, River Nile and Red Sea states, respectively. The 3D7 allelic family was more prevalent in the states of Khartoum, Gezira, River Nile and Red Sea compared to the FC27 allelic family. Multiclonal infections were observed in 25.8% of patients, with a mean multiplicity of infection (MOI) of 1.45. MOIs were highest in the age group over 40, with an average of 2 and 1.68 in Khartoum and Gezira states, respectively, however MOIs in River Nile and Red Sea states were higher in age groups below 18, with an average of 1.37 and 1.33, respectively. Conclusions: MSP2 allelic genotyping revealed MOI and diversity of the Sudanese P. falciparum isolates. The results of our study are expected to influence current and future malaria control strategies, since the MOI predicts development of clinical malaria and subsequent efficacy of antimalarial treatment.