bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase
Authors: Sun Song , Weile Jochen , Verby Marta , Cote Atina G. , Wu Yingzhou , Fotiadou Iosifina , Kitaygorodsky Julia , Rine Jasper , Ješina Pavel , Kožich Viktor , Roth Frederick P. 
Published: November 2018

AbstractSuccess in precision medicine depends on our ability to determine which rare human genetic variants have functional effects. Classical homocystinuria—characterized by elevated homocyst(e)ine in plasma and urine—is caused by primarily-rare variants in the cystathionine beta-synthase (CBS) gene. About half of patients respond to vitamin B6therapy. With early detection in newborns, existing therapies are highly effective. FunctionalCBSvariants, especially those that respond to vitamin B6, can be detected based on their ability to restore growth in yeast cells lackingCYS4 (the yeast ortholog ofCBS). This assay has previously been carried out only ‘reactively’ after first observation of a variant in patients. Here we describe a ‘proactive’ comprehensive missense variant effect map for human CBS. Together, saturation codon-replacement mutagenesis,en massegrowth selection at different vitamin B6levels, and sequencing yielded a ‘look-up table’ for CBS missense variant function and vitamin B6-remediability in yeast. The CBS variant effect map identified disease variants and predicted both disease severity (r= 0.82) and human clinical response to vitamin B6(r= 0.89). Thus, highly-multiplexed cell-based assays can yield proactive maps of variant function and patient response to therapy, even for rare variants not previously seen in the clinic.
Rac-dependent signaling from keratinocytes promotes differentiation of intradermal white adipocytes
Authors: Ueyama Takehiko , Sakuma Megumi , Nakatsuji Mio , Uebi Tatsuya , Hamada Takeshi , Aiba Atsu , Saito Naoaki 
Published: November 2018

AbstractRac signaling affects numerous downstream targets; however, few studies have established in vivo levels. We generated mice with a single knockout (KO) of Rac1 (Keratin5 (K5)-Cre;Rac1flox/flox, Rac1-KO) and double KO of Rac1 and Rac3 (K5-Cre;Rac1flox/flox;Rac3−/−, Rac1/Rac3-DKO) in keratinocytes. Strikingly, Rac1-KO mice exhibited thinner dermal white adipose tissue, which was considerably further reduced in Rac1/Rac3-DKO mice. DNA microarray using primary keratinocytes from Rac1/Rac3-DKO mice exhibited decreased mRNA levels of Bmp2, Bmp5, Fgf20, Fgf21, Fgfbp1, and Pdgfα. Combinational treatment with BMP2 and FGF21 or BMP2 and FGF20 in culture medium, but not individual purified recombinant proteins, could differentiate 3T3-L1 fibroblasts into adipocytes, as could culture media obtained from primary keratinocytes. Conversely, addition of anti-BMP2 or anti-FGF21 antibodies into the culture medium inhibited fibroblast differentiation. Furthermore, combinational treatment with BMP2 and FGF21 promoted adipocyte differentiation only of rat primary white, but not brown, adipocyte precursors. Notably, brown adipogenesis by FGF21 was inhibited by BMP2. Thus, we proposed novel paracrine pathways from keratinocytes to intradermal pre-adipocytes, which function as Rac-dependent modulators of white adipogenesis, but also brown adipogenesis.
Elevation of intracellular levels of nitric oxide in SHR attenuates hyperproliferation of vascular smooth muscle cells through the inhibition of AT1 receptor expression and c-Src/growth factor receptor signaling pathways
Authors: Hossain Ekhtear , Sarkar Oli , Li Yuan , Anand-Srivastava Madhu B. 
Published: November 2018

AbstractWe previously showed that decreased levels of intracellular nitric oxide (NO) contribute to the hyperproliferation of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). The present study investigates if elevation of intracellular levels of NO by in vivo treatment of SHR with NO donor, sodium nitroprusside (SNP) that was shown to attenuate hypertension could attenuate the hyperproliferation of VSMC and identify the molecular mechanisms. Intraperitoneal injection of SNP (0.5 mg/kg BW) into 8-week-old SHR and WKY rats twice a week for two weeks increased significantly the intracellular levels of NO in aortic VSMC and resulted in the attenuation of hyperproliferation of VSMC from SHR to control levels. The antiproliferative effect of SNP was associated with the restoration of the overexpression of cell cycle proteins, cyclins D1, E, Cdk2, Cdk4, phosphorylated pRB and decreased expression of Cdk inhibitors p21Cip1 and p27Kip1 towards control levels. In addition, SNP treatment also attenuated the overexpression of angiotensin II receptor type 1 (AT1) receptor, phosphorylation of c-Src, EGF-R, PDGF-R, IGF-IR and ERK1/2 in VSMC from SHR to control levels. These results suggest that the augmentation of intracellular levels of NO elicits antiproliferative effect that may be mediated through its ability to inhibit the enhanced expression of AT1 receptor, activation of c- Src, growth factor receptors and MAP kinase signaling and overexpression of cell cycle proteins.
The idiosyncratic drivers of correlated evolution
Authors: Dench Jonathan , Hinz Aaron , Aris-Brosou Stéphane , Kassen Rees 
Published: November 2018

AbstractThe ultimate causes of correlated evolution among sites in a genome remain difficult to tease apart. To address this problem directly, we performed a high-throughput search for correlated evolution among sites associated with resistance to a fluoroquinolone antibiotic using whole genome data from clinical strains ofPseudomonas aeruginosa, before validating our computational predictions experimentally. We show that for at least two sites, this correlation is underlain by epistasis. Our analysis also revealed eight additional pairs of synonymous substitutions displaying correlated evolution underlain by physical linkage, rather than selection associated with antibiotic resistance. Our results provide direct evidence that both epistasis and physical linkage among sites can drive the correlated evolution identified by high throughput computational tools. In other words, the observation of correlated evolution is not by itself sufficient evidence to guarantee that the sites in question are epistatic; such a claim requires additional evidence, ideally coming from direct estimates of epistasis, based on experimental evidence.
Real exchange rate misalignment and economy
Authors: Wong Hock Tsen 
Published: November 2018

PurposeThe purpose of this paper is to examine the impact of real exchange rate misalignment on economy and economic sectors, namely construction, manufacturing and mining and quarrying in Malaysia.Design/methodology/approachThe equilibrium real exchange rate and economic models are estimated using the autoregressive distributed lag approach.FindingsAn increase in productivity differential or reserve differential will lead to an appreciation of real exchange rate in the long run. An increase in positive (negative) real exchange rate misalignment will lead to an increase (decrease) in economy. An increase in long-run real exchange rate misalignment will lead to a decrease in economy. Real exchange rate misalignment or long-run real exchange rate misalignment can influence the manufacturing sector in Malaysia. More specifically, undervaluation will promote whereas overvaluation will hurt the manufacturing sector.Originality/valueReal exchange rate misalignment can be a policy to influence economy but may not be the best choice.
Environmental Kuznets curve for CO2 emissions: a literature survey
Authors: Shahbaz Muhammad , Sinha Avik 
Published: November 2018

Purpose
The purpose of this paper is to provide a survey of the empirical literature on environmental Kuznets curve (EKC) estimation of carbon dioxide (CO2) emissions over the period of 1991–2017.

Design/methodology/approach
This survey categorizes the studies on the basis of power of income in empirical models of EKC. It has been hypothesized that the EKC shows an inverted U-shaped association between economic growth and CO2 emissions.

Findings
For all the contexts, the results of EKC estimation for CO2 emissions are inconclusive in nature. The reasons behind this discrepancy can be attributed to the choice of contexts, time period, explanatory variables, and methodological adaptation.

Research limitations/implications
The future studies in this context should not only consider new set of variables (e.g. corruption index, social indicators, political scenario, energy research and development expenditures, foreign capital inflows, happiness, population education structure, public investment toward alternate energy exploration, etc.), but also the data set should be refined, so that the EKC estimation issues raised by Stern (2004) can be addressed.

Originality/value
By far, no study in the literature of ecological economics has focused on the empirical estimation of EKC for CO2 emissions. This particular context has been used for this study, as CO2 is one of the highest studied pollutants in the ecological economics, and especially within the EKC hypothesis framework.
West African strangers and the politics of inhumanity in Angola
Authors: GAIBAZZI PAOLO 
Published: November 2018

ABSTRACTSince 2002, Angola has increasingly resorted to illegalization, deportation, and predatory policing to manage immigration. The resulting abuses lead Muslim West African migrants, especially those from the Mande ethnolinguistic area, to denounce Angola's lack of “humanity.” Their takes on inhumanity cannot be sufficiently explained by either conventional understandings of human rights or biopolitical theories of legal exclusion and bare life. Instead, Mande notions of hospitality, empathy, and the “human right” to survival enable migrants to navigate Angola's regimes of clientelism. Inhumanity results from the state's repression and predation, which prevent migrants from negotiating with their “hosts” on affective‐ethical grounds rather than solely on legal ones. Departing from Western Enlightenment, Mande humanism provides an alternative perspective from the South for analyzing how life and politics connect. [empathy, migrant illegality, deportation, humanism, hospitality, human rights, West African traders, Mande, Angola]
Systematic review of the applications of three‐dimensional printing in colorectal surgery
Authors: Emile S. H. , Wexner S. D. 
Published: November 2018

AbstractAimThree‐dimensional (3D) printing has been recognized as a revolutionary technological innovation that has benefitted numerous disciplines, including medicine. The present systematic review aimed to demonstrate the current applications of 3D printing in colorectal surgery along with the limitations and potential future applications of this innovation.MethodA PRISMA‐compliant systematic literature search of studies that applied 3D printing in colorectal surgery in the period from January 1990 to July 2018 was conducted. Electronic databases including PubMed/Medline, Scopus and the Cochrane Library were searched. All full‐text original articles were eligible for inclusion.ResultsNine studies including 58 patients with a median age of 60.7 years were reviewed. The studies assessed 3D printing in patients with planned stoma construction, colon cancer with liver metastasis, right colon cancer, rectal cancer, intractable constipation and anal fistula. The applications of 3D printing were classified into three categories: patient education, preoperative planning and evaluation of response of colorectal liver metastasis to chemotherapy. 3D printed models aided in planning resection of colorectal liver metastasis, facilitating D3 lymphadenectomy in complete mesocolic excision, improving the understanding of pelvic anatomy in laparoscopic rectal cancer treatment, guiding electrode implantation in sacral neuromodulation for intractable constipation, and elucidating the morphology of anal fistula tract and anal sphincter muscles.ConclusionColorectal surgery may benefit from 3D printing in enhancing patient education before stoma construction, preoperative planning and evaluation of the response of liver metastasis to chemotherapy using 3D ultrasonography.
Repeated blast model of mild traumatic brain injury alters oxycodone self‐administration and drug seeking
Authors: Nawarawong Natalie N. , Slaker Megan , Muelbl Matt , Shah Alok S. , Chiariello Rachel , Nelson Lindsay D. , Budde Matthew D. , Stemper Brian D. , Olsen Christopher M. 
Published: November 2018

AbstractEach year, traumatic brain injuries (TBI) affect millions worldwide. Mild TBIs (mTBI) are the most prevalent and can lead to a range of neurobehavioral problems, including substance abuse. A single blast exposure, inducing mTBI alters the medial prefrontal cortex, an area implicated in addiction, for at least 30 days post injury in rats. Repeated blast exposures result in greater physiological and behavioral dysfunction than single exposure; however, the impact of repeated mTBI on addiction is unknown. In this study, the effect of mTBI on various stages of oxycodone use was examined. Male Sprague Dawley rats were exposed to a blast model of mTBI once per day for 3 days. Rats were trained to self‐administer oxycodone during short (2 h) and long (6 h) access sessions. Following abstinence, rats underwent extinction and two cued reinstatement sessions. Sham and rbTBI rats had similar oxycodone intake, extinction responding and cued reinstatement of drug seeking. A second group of rats were trained to self‐administer oxycodone with varying reinforcement schedules (fixed ratio (FR)‐2 and FR‐4). Under an FR‐2 schedule, rbTBI‐exposed rats earned fewer reinforcers than sham‐exposed rats. During 10 extinction sessions, the rbTBI‐exposed rats exhibited significantly more seeking for oxycodone than the sham‐injured rats. There was a positive correlation between total oxycodone intake and day 1 extinction drug seeking in sham, but not in rbTBI‐exposed rats. Together, this suggests that rbTBI‐exposed rats are more sensitive to oxycodone‐associated cues during reinstatement than sham‐exposed rats and that rbTBI may disrupt the relationship between oxycodone intake and seeking.
Connecting the public with soil to improve human health
Authors: Brevik Eric C. , Steffan Joshua J. , Rodrigo‐Comino Jesús , Neubert Darrell , Burgess Lynn C. , Cerdà Artemi 
Published: November 2018

Despite the definite links between soil and human health, it is likely that most people do not think about soil when considering human health. There is a disconnect between most people in our modern society and soil, and when people notice soil it is often in a negative context. People care for things that matter to them, and creating a more positive public image of soil could improve human health by leading to better treatment and understanding of the soil resource. There are a number of concepts that may be able to connect people to the soil, including terroir, soil health and soil security. While terroir originally established a connection between those who appreciate wine and the soils that produce those wines, the concept has been expanded to many additional products. It might be possible to provide a terroir link to human health benefits if they can be shown to be characteristic of a given soil environment. The concept of soil health has caught on with many farmers, policymakers, scientists and the general public, thus providing another possible approach to improve peoples’ connection with soil. Soil security is a recent concept that has been advanced as a way to take advantage of the connection that concepts such as energy, food and water security have made with policymakers. Therefore, we advocate a concerted effort to investigate terroir, soil health and soil security as concepts to improve overall human health. Soil health and soil security might have the most promise, and some social marketing campaigns that include soil health are ongoing.Highlights
Soil is important to human health.
A disconnect exists between the urban population and soil.
Education about soil can rebuild these connections.
Concepts such as terroir, soil health or soil security might help make connections.
Selection and optimization of a suitable pretreatment method for miscanthus and poplar raw material
Authors: Seibert‐Ludwig Daniel , Hahn Thomas , Hirth Thomas , Zibek Susanne 
Published: November 2018

AbstractMiscanthus and poplar are very promising second‐generation feedstocks due to the high growth rates and low nutrient demand. The aim of the study was to develop a systematic approach for choosing suitable pretreatment methods evaluated with the modified severity factor (log ). Optimal pretreatment results in a high delignification grade, low cellulose solubilization and increased accessibility for enzymatic hydrolysis while revealing minimal log values. In order to do so, several reaction approaches were compared. Acid‐catalyzed organosolv processing carried out for miscanthus and poplar revealed the highest delignification grade leading to a relatively high glucose yield after enzymatic saccharification. In both cases, a design of experiments approach was used to study the influence of relevant parameters. Modeling the data resulted in the identification of optimum pretreatment conditions for miscanthus with concentrations of 0.16% H2SO4 and 50% EtOH at 185°C for a retention time of 60 min. Experimental validation of these conditions revealed an even higher delignification degree (88%) and glucose yield (85%) than predicted. 0.19% H2SO4 and 50% EtOH were determined as optimum concentrations, 182°C and 48 min identified as optimum pretreatment conditions for poplar; the delignification degree was 84% and the resulting glucose yield 70%.
An evaluation of mainstream type 2 diabetes educational programmes in relation to the needs of people with intellectual disabilities: A systematic review of the literature
Authors: Maine Andrew , Brown Michael J. , Dickson Adele , Truesdale Maria 
Published: November 2018

AbstractBackgroundRisk reduction and self‐management programs for type 2 diabetes (T2D) are commonplace. However, little is known about their appropriateness for people with intellectual disabilities (ID). This review evaluates successful components and theoretical basis of interventions and preventions in relation to the needs of people with ID with or at risk of T2D.MethodCharacteristics of 23 randomised controlled trialled T2D educational programs were systematically assessed alongside the needs of people with ID, and evaluated in terms of study design and theoretical application.ResultsSuccessful components of programs align to the needs of people with ID. Further adaptations are required to ensure accessibility of materials and social support to enable reflection on illness perceptions and self‐efficacy, as underpinned by Self‐regulation and Social‐cognitive theories.ConclusionsSupport is provided for further trials of self‐management and preventative adaptations under development. Impact may be enhanced through preventions aimed at younger groups in educational settings.
Exercise during transition from compensated left ventricular hypertrophy to heart failure in aortic stenosis rats
Authors: Reyes David R. A. , Gomes Mariana J. , Rosa Camila M. , Pagan Luana U. , Zanati Silmeia G. , Damatto Ricardo L. , Rodrigues Eder A. , Carvalho Robson F. , Fernandes Ana A. H. , Martinez Paula F. , Lima Aline R. R. , Cezar Marcelo D. M. , Carvalho Luiz E. F. M. , Okoshi Katashi , Okoshi Marina P. 
Published: November 2018

AbstractWe evaluated the influence of aerobic exercise on cardiac remodelling during the transition from compensated left ventricular (LV) hypertrophy to clinical heart failure in aortic stenosis (AS) rats. Eighteen weeks after AS induction, rats were assigned into sedentary (AS) and exercised (AS‐Ex) groups. Results were compared to Sham rats. Exercise was performed on treadmill for 8 weeks. Exercise improved functional capacity. Echocardiogram showed no differences between AS‐Ex and AS groups. After exercise, fractional shortening and ejection fraction were lower in AS‐Ex than Sham. Myocyte diameter and interstitial collagen fraction were higher in AS and AS‐Ex than Sham; however, myocyte diameter was higher in AS‐Ex than AS. Myocardial oxidative stress, evaluated by lipid hydroperoxide concentration, was higher in AS than Sham and was normalized by exercise. Gene expression of the NADPH oxidase subunits NOX2 and NOX4, which participate in ROS generation, did not differ between groups. Activity of the antioxidant enzyme superoxide dismutase was lower in AS and AS‐Ex than Sham and glutathione peroxidase was lower in AS‐Ex than Sham. Total and reduced myocardial glutathione, which is involved in cellular defence against oxidative stress, was lower in AS than Sham and total glutathione was higher in AS‐Ex than AS. The MAPK JNK was higher in AS‐Ex than Sham and AS groups. Phosphorylated P38 was lower in AS‐Ex than AS. Despite improving functional capacity, aerobic exercise does not change LV function in AS rats. Exercise restores myocardial glutathione, reduces oxidative stress, impairs JNK signalling and further induces myocyte hypertrophy.
International comparison of trends in patients commencing renal replacement therapy by primary renal disease
Authors: Stel Vianda S , Awadhpersad Ryan , Pippias Maria , Ferrer‐Alamar Manuel , Finne Patrik , Fraser Simon D , Heaf James G , Hemmelder Marc H , Martínez‐Castelao Alberto , de Meester Johan , Palsson Runolfur , Prischl Friedrich C , Segelmark Mårten , Traynor Jamie P , Santamaria Rafael , Reisæter Anna Varberg , Massy Ziad A , Jager Kitty J 
Published: November 2018

ABSTRACTAimTo examine international time trends in the incidence of renal replacement therapy (RRT) for end‐stage renal disease (ESRD) by primary renal disease (PRD).MethodsRenal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression.ResultsThere was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC = −0.9; 95%CI −1.3; −0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC = −1.8; 95%CI −3.3; −0.3), Canada (AAPC = −2.9; 95%CI −4.4; −1.5) and Europe (AAPC = −1.1; 95%CI −2.1; −0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2–16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea.ConclusionLarge international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD.