bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five eighteenth-century medical polymaths
Authors: Hull Gillian C. 
Published: November 2012

Abstract
Five eighteenth-century medical men, like many of their contemporaries, achieved renown for their medical skills and research abilities. They lived during an exciting period marked by the questioning of many traditional beliefs. Coeval scientific achievements increased knowledge of the challenging natural world around them. Outside medicine, John Wall (1708–1776) established the fashionable spa of Malvern, known for the purity of its water, and co-founded the prestigious Worcester Porcelain Company. Erasmus Darwin (1731–1802) had a remarkably inventive mind ranging over many interests, including canal construction, steering equipment for carriages and a copying machine for documents. Edward Jenner (1749–1823) was interested in bird migration, and researched the brood parasitism of the cuckoo. His vaccination of cowpox to prevent smallpox eventually led to the elimination of the disease in 1980. Caleb Parry (1755–1822) practised medicine in Bath and was admired for his knowledge and integrity. He was interested in sheep and produced high-quality merino wool. Since boyhood he had hunted for fossils with his friend, Edward Jenner. John MacCulloch (1773–1835) produced the first geological map of Scotland, published posthumously in 1836. A prolific writer, his book on the Western Isles (1819) is considered a classic.
The influence of geology in the development of public health
Authors: Bergman Beverly P. 
Published: November 2012

Abstract
Public health, the protection of the health of populations through community engagement, is a modern specialty originating in post-Industrial Revolution Britain, while environmental geochemistry is of even more recent origin. The influence of geology on health was first recognized in Classical times, although it was later supplanted by the miasma theory of disease. During the Renaissance, medical teaching began to concentrate more on diagnosis and treatment of the sick individual and less on preserving the health of populations. The concept of geology as a determinant of health re-emerged with the growth of scientific knowledge during the Enlightenment period of the eighteenth century. The nineteenth century saw the first identification of trace element deficiency disease and the publication of a textbook of public health which described geological influences on health. Over the next 100 years both public health and environmental geochemistry became established on a firm footing, although as separate disciplines. Recently the public health focus has been on lifestyle choices, but environmental geochemistry remains a potentially powerful partner in the fight to protect health, and there is much scope to enhance collaborative working. The legacy of the pioneers of both public health and geology must not be forgotten.
KRAS Testing and Epidermal Growth Factor Receptor Inhibitor Treatment for Colorectal Cancer in Community Settings
Authors: Webster Jennifer , Kauffman Tia L. , Feigelson Heather Spencer , Pawloski Pamala A. , Onitilo Adedayo A. , Potosky Arnold L. , Cross Deanna , Meier Paul R. , Mirabedi Anousheh S. , Delate Thomas , Daida Yihe , Williams Andrew E. , Alexander Gwen L. , McCarty Catherine A. , Honda Stacey , Kushi Lawrence H. , Goddard Katrina A.B. ,   on behalf of the CERGEN study team
Published: November 2012

Abstract
Background: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing.
Methods: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care.
Results: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P &lt; 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009).
Conclusions: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care.
Impact: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States. Cancer Epidemiol Biomarkers Prev; 22(1); 91–101. ©2012 AACR.
Double-Nested Dynamical Downscaling Experiments over the Tibetan Plateau and Their Projection of Climate Change under Two RCP Scenarios
Authors: Ji Zhenming , Kang Shichang 
Published: November 2012

AbstractA high-resolution regional climate model is used to simulate climate change over the Tibetan Plateau (TP). The model is driven at the grid spacing of 10 km by nesting the outputs of 50-km-resolution simulations. The results show that the models can capture the spatial and temporal distributions of the surface air temperature over the TP. The so-called double-nested method has a higher horizontal resolution and represents more spatial details. For example, the temperature simulations from the double-nested method reflect the observations better compared to the 50-km-resolution models. This is mainly due to the fact that topographical effects of complex terrains are detected better at higher resolution. Although both models can represent the basic patterns of precipitation, the simulated results are not as good as those of temperature. In the future, significant warming seems to develop over the TP under two representative concentration pathway (RCP) scenarios. Greater increases occur in December–February (DJF) compared with June–August (JJA). The increasing temperature trend is more pronounced over the Gangdese Mountains and over the Himalayas than in the central TP. The projection of precipitation shows the main increases in DJF. In JJA, it predicts decreases or slight changes in the southern TP. The comparison between RCP8.5 and RCP4.5 scenarios shows a similar spatial distributions of temperature and precipitation, whereas the respective values of RCP8.5 are enhanced compared with those under RCP4.5.
Relationship between Air–Sea Density Flux and Isopycnal Meridional Overturning Circulation in a Warming Climate
Authors: Han MyeongHee , Kamenkovich Igor , Radko Timour , Johns William E. 
Published: November 2012

Abstract
This study aims to explore the relationship between air–sea density flux and isopycnal meridional overturning circulation (MOC), using the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) model projections of the twenty-first-century climate. The focus is on the semiadiabatic component of MOC beneath the mixed layer; this component is described using the concept of the push–pull mode, which represents the combined effects of the adiabatic push into the deep ocean in the Northern Hemisphere and the pull out of the deep ocean in the Southern Hemisphere. The analysis based on the GFDL Climate Model version 2.1 (CM2.1) simulation demonstrates that the push–pull mode and the actual isopycnal MOC at the equator evolve similarly in the deep layers, with their maximum transports decreasing by 4–5 Sv (1 Sv ≡ 106 m3 s−1) during years 2001–2100. In particular, the push–pull mode and actual isopycnal MOC are within approximately 10% of each other at the density layers heavier than 27.55 kg m−3, where the reduction in the MOC strength is the strongest. The decrease in the push–pull mode is caused by the direct contribution of the anomalous heat, rather than freshwater, surface fluxes. The agreement between the deep push–pull mode and MOC in the values of linear trend and variability on time scales longer than a decade suggests a largely adiabatic pole-to-pole mechanism for these changes. The robustness of the main conclusions is further explored in additional model simulations.
Strong Dynamical Modulation of the Cooling of the Polar Stratosphere Associated with the Antarctic Ozone Hole
Authors: Orr Andrew , Bracegirdle Thomas J. , Hosking J. Scott , Feng Wuhu , Roscoe Howard K. , Haigh Joanna D. 
Published: November 2012

Abstract
A model simulation forced by prescribed ozone depletion shows strong dynamical modulation of the springtime cooling of the polar stratosphere associated with the Antarctic ozone hole. The authors find that in late spring the anomalous radiative cooling in response to ozone depletion is almost canceled above ~100 hPa by an increase in dynamical heating. Between ~300 and ~100 hPa, however, it is enhanced by a reduction in dynamical heating, resulting in the descent of the cold anomaly down to the tropopause. In early summer increased dynamical heating dominates as the radiative cooling diminishes so that the cold anomaly associated with the delayed breakup of the stratospheric vortex is reduced. The anomalous dynamical heating is driven by changes in the Brewer–Dobson circulation arising primarily from the dissipation of resolved-scale waves. The model changes are broadly consistent with trends from reanalysis and offline diagnoses of heating rates using a radiation scheme. These results help one to understand dynamically induced change in the evolution and timing of the stratospheric vortex in recent decades and will help to enable improved simulation of the Southern Hemisphere climate.
On the Robustness of Emergent Constraints Used in Multimodel Climate Change Projections of Arctic Warming
Authors: Bracegirdle Thomas J. , Stephenson David B. 
Published: November 2012

Abstract
Statistical relationships between future and historical model runs in multimodel ensembles (MMEs) are increasingly exploited to make more constrained projections of climate change. However, such emergent constraints may be spurious and can arise because of shared (common) errors in a particular MME or because of overly influential models. This study assesses the robustness of emergent constraints used for Arctic warming by comparison of such constraints in ensembles generated by the two most recent Coupled Model Intercomparison Project (CMIP) experiments: CMIP3 and CMIP5. An ensemble regression approach is used to estimate emergent constraints in Arctic wintertime surface air temperature change over the twenty-first century under the Special Report on Emission Scenarios (SRES) A1B scenario in CMIP3 and the Representative Concentration Pathway (RCP) 4.5 scenario in CMIP5. To take account of different scenarios, this study focuses on polar amplification by using temperature responses at each grid point that are scaled by the global mean temperature response for each climate model. In most locations, the estimated emergent constraints are reassuringly similar in CMIP3 and CMIP5 and differences could have easily arisen from sampling variation. However, there is some indication that the emergent constraint and polar amplification is substantially larger in CMIP5 over the Sea of Okhotsk and the Bering Sea. Residual diagnostics identify one climate model in CMIP5 that has a notable influence on estimated emergent constraints over the Bering Sea and one in CMIP3 that that has a notable influence more widely along the sea ice edge and into midlatitudes over the western North Atlantic.
Migraine and restless legs syndrome in men
Authors: Winter Anke C , Schürks Markus , Berger Klaus , Buring Julie E , Gaziano J Michael , Kurth Tobias 
Published: November 2012

Background Previous studies suggest an association between migraine and restless legs syndrome (RLS). Population-based data, however, have been limited to women. The aim of this study is to evaluate the association between migraine and RLS in a male cohort. Methods We conducted a cross-sectional study among 22,926 participants in the Physicians’ Health Study. Migraine and RLS information was self-reported. RLS was classified according to four minimal diagnostic criteria. Age- and multivariable-adjusted logistic regression models were calculated. Results Of the 22,926 participants (mean age 67.8), 2816 (12.3%) reported migraine and 1717 (7.5%) RLS. Migraine was associated with an increased multivariable-adjusted odds ratio (OR) (95% confidence interval (CI)) of 1.20 (1.04–1.38) for having RLS. The association remained stable after excluding men with potential mimics of RLS and was not modified by age. Conclusions Results of our study indicate an association between migraine and RLS in men. The magnitude of effect is similar to what has been reported in women.
NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits CGRP release in preclinical migraine models
Authors: Bhatt Deepak K , Gupta Saurabh , Jansen-Olesen Inger , Andrews John S , Olesen Jes 
Published: November 2012

Background NXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist. Using preclinical models, we evaluated whether these two unique therapeutic principles have a synergistic effect in attenuating stimulated calcitonin gene-related peptide (CGRP) release, a marker of trigeminal activation. Methods We examined the effect of NXN-188 on: (1) KCl-, capsaicin- and resiniferatoxin (RTX)-induced immunoreactive CGRP (iCGRP) release from isolated preparation of rat dura mater, trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC); and (2) capsaicin- and electrical stimulation (ES)-induced middle meningeal artery (MMA) dilation in a rat closed-cranial window. Results NXN-188 inhibited: (1) KCl-stimulated iCGRP release from dura mater (% decrease mean ± SEM, lowest effective concentration) (35 ± 6%, 30 µM), TG (24 ± 11 %, 10 µM) and TNC (40 ± 8%, 10 µM); (2) capsaicin- and RTX-induced iCGRP release from dura mater; and (3) capsaicin- and ES-induced increase in dural artery diameter (32 ± 5%, 3 mg kg−1 intravenous (i.v.) and 36 ± 1%, 10 mg kg−1 i.v.). Conclusions NXN-188 inhibits CGRP release from migraine-relevant cephalic tissues. Its effect is most likely mediated via a combination of nNOS-inhibition and 5-HT1B/1D receptor agonism in dura mater while the mechanisms of action for inhibition of CGRP release from TG and TNC have to be investigated further.
The scintigraphic evaluation and genetic correlation of joint involvements in pediatric patients with familial Mediterranean fever
Authors: Aydogan F. , Tutanc M. , Arica V. , Arica S. , Gunesacar R. 
Published: November 2012

Purpose: We aimed to evaluate the articular involvements in pediatric patients with familial Mediterranean fever (FMF) with joint symptoms by bone scintigraphy and to correlate the involved joints with the gene mutations. Materials and methods: A total of 41 newly diagnosed patients in pediatric age group (28 girls and 13 boys; mean age 9.14 ± 2.91 years) with joint involvement symptoms were included in this study. Scintigraphic images were obtained at 5th min (blood pool or early phase) and starting at 3 h (late phase) after (after tracer injection) intravenous administration of technetium-99m (99mTc)-methylendiphosphonate (MDP). Genomic DNA was isolated from leukocytes using standard salting out procedure. The sequencing data were analyzed. Results: Of the 41 patients, arthritis was found in 21 (51.2%) patients. Of the 21 patients, there was single joint involvement in 15 (71.4%) patients and multiple joint involvement in six (28.6%) patients. The mean age of patients with joint involvement (8 ± 2.3 years) were considerably lower than the patients without joint involvement (10.35 ± 3.04 years), and this was statistically significant ( p = 0.008). The most commonly involved joints were ankles and knees. Multiple joint involvements were most frequently observed in the M694V and M694I gene mutations (16.7%). Conclusions: We use and recommend the bone scintigraphy in patients with FMF to determine the presence and distribution of arthritis, since bone scintigraphy is inexpensive, noninvasive, easy-to-use, and also is more sensitive in the diagnosis and distribution of arthritis than conventional radiological methods and clinical examination.
Effect of lifestyles on the blood mercury level in Korean adults
Authors: Kim N-Y , Ahn S-J , Ryu D-Y , Choi B-S , Kim H , Yu I-J , Park J-D 
Published: November 2012

Mercury (Hg) is widely distributed in the environment and oral exposure is a main route in the general population. In this study, we estimated the dietary intake of Hg and its relationship with blood Hg levels in Korean adults. The study subjects were recruited from three different districts (rural: 189, coastal: 208 and urban: 184). We used a general questionnaire to collect information about demographic factors, lifestyles and diet. Dietary habits were studied using the 24-h recall method. The estimation of Hg intake was performed using the database of Hg contents in 128 Korean foods based on the previous studies. Blood Hg was analyzed using Direct Mercury Analyzer with the gold-amalgam method. Daily intake of Hg by diet was estimated at 13.57 μg (0.22 μg/kg body weight). The geometric mean Hg concentration in whole blood was 3.92 μg/L. Blood Hg level and Hg intake by diet was higher in coastal areas than in urban or rural areas, respectively. Blood Hg level correlated with the intake of Hg consumed from diet. Seafood was highly responsible and account for 75.6% of total dietary Hg intake. In this study, blood Hg concentrations were found to be significantly affected by sex, age, individual lifestyles and especially the amount of seafood intake, which might play an important role in determining blood Hg levels in Korean adults.
Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous cyanobacteria
Authors: Cui Hongli , Wang Yipeng , Wang Yinchu , Qin Song 
Published: November 2012

Abstract

Background
Cyanobacteria are photoautotrophic prokaryotes with wide variations in genome sizes and ecological habitats. Peroxiredoxin (PRX) is an important protein that plays essential roles in protecting own cells against reactive oxygen species (ROS). PRXs have been identified from mammals, fungi and higher plants. However, knowledge on cyanobacterial PRXs still remains obscure. With the availability of 37 sequenced cyanobacterial genomes, we performed a comprehensive comparative analysis of PRXs and explored their diversity, distribution, domain structure and evolution.

Results
Overall 244 putative prx genes were identified, which were abundant in filamentous diazotrophic cyanobacteria, Acaryochloris marina MBIC 11017, and unicellular cyanobacteria inhabiting freshwater and hot-springs, while poor in all Prochlorococcus and marine Synechococcus strains. Among these putative genes, 25 open reading frames (ORFs) encoding hypothetical proteins were identified as prx gene family members and the others were already annotated as prx genes. All 244 putative PRXs were classified into five major subfamilies (1-Cys, 2-Cys, BCP, PRX5_like, and PRX-like) according to their domain structures. The catalytic motifs of the cyanobacterial PRXs were similar to those of eukaryotic PRXs and highly conserved in all but the PRX-like subfamily. Classical motif (CXXC) of thioredoxin was detected in protein sequences from the PRX-like subfamily. Phylogenetic tree constructed of catalytic domains coincided well with the domain structures of PRXs and the phylogenies based on 16s rRNA.

Conclusions
The distribution of genes encoding PRXs in different unicellular and filamentous cyanobacteria especially those sub-families like PRX-like or 1-Cys PRX correlate with the genome size, eco-physiology, and physiological properties of the organisms. Cyanobacterial and eukaryotic PRXs share similar conserved motifs, indicating that cyanobacteria adopt similar catalytic mechanisms as eukaryotes. All cyanobacterial PRX proteins share highly similar structures, implying that these genes may originate from a common ancestor. In this study, a general framework of the sequence-structure-function connections of the PRXs was revealed, which may facilitate functional investigations of PRXs in various organisms.
Dynamics of domain coverage of the protein sequence universe
Authors: Rekapalli Bhanu , Wuichet Kristin , Peterson Gregory D , Zhulin Igor B 
Published: November 2012

Abstract

Background
The currently known protein sequence space consists of millions of sequences in public databases and is rapidly expanding. Assigning sequences to families leads to a better understanding of protein function and the nature of the protein universe. However, a large portion of the current protein space remains unassigned and is referred to as its “dark matter”.

Results
Here we suggest that true size of “dark matter” is much larger than stated by current definitions. We propose an approach to reducing the size of “dark matter” by identifying and subtracting regions in protein sequences that are not likely to contain any domain.

Conclusions
Recent improvements in computational domain modeling result in a decrease, albeit slowly, in the relative size of “dark matter”; however, its absolute size increases substantially with the growth of sequence data.
Directional telomeric silencing and lack of canonical B1 elements in two silencer Autonomously Replicating Sequences in S. cerevisiae
Authors: Chisamore-Robert Patricia , Peeters Samantha , Shostak Kristina , Yankulov Krassimir 
Published: November 2012

Abstract

Background
Autonomously Replicating Sequences (ARS) in S. cerevisiae serve as origins of DNA replication or as components of cis-acting silencers, which impose positional repression at the mating type loci and at the telomeres. Both types of ARS can act as replicators or silencers, however it is not clear how these quite diverse functions are executed. It is believed that all ARS contain a core module of an essential ARS Consensus Sequence (ACS) and a non-essential B1 element.

Results
We have tested how the B1 elements contribute to the silencer and replicator function of ARS. We report that the ACS-B1 orientation of ARS has a profound effect on the levels of gene silencing at telomeres. We also report that the destruction of the canonical B1 elements in two silencer ARS (ARS317 and ARS319) has no effect on their silencer and replicator activity.

Conclusions
The observed orientation effects on gene silencing suggest that ARSs can act as both proto-silencers and as insulator elements. In addition, the lack of B1 suggests that the ACS-B1 module could be different in silencer and replicator ARS.