bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis
Authors: Wolf Myles , Block Geoffrey A , Chertow Glenn M , Cooper Kerry , Fouqueray Bruno , Moe Sharon M , Sun Yan , Tomlin Holly , Vervloet Marc , Oberbauer Rainer 
Published: March 2019

Abstract

Background
Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown.

Methods
To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide.

Results
Etelcalcetide reduced FGF23 [median % change (quartile 1–quartile 3)] from baseline to the end of the trial significantly more than placebo [–56% (–85 to –7) versus +2% (–40 to +65); P &lt; 0.001] and cinacalcet [–68% (–87 to –26) versus –41% (–76 to +25); P &lt; 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide.

Conclusion
These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium.
The investigative burden of membranous nephropathy in the UK
Authors: Hamilton Patrick , Wilson Fiona , Chinnadurai Rajkumar , Sinha Smeeta , Singh Malinder , Ponnusamy Arvind , Hall Peter , Dhaygude Ajay , Kanigicherla Durga , Brenchley Paul 
Published: March 2019

Abstract

Background
Membranous nephropathy (MN) represents two distinct disease entities. Primary MN is now recognized as an autoimmune condition associated with the anti-PLA2R antibody and secondary MN occurs in tandem with malignancy, infection, drug therapy and other autoimmune conditions. Prior to the development of accessible enzyme-linked immunosorbent assays, the diagnosis of MN was one of exclusion. We studied whether the introduction of serum anti-PLA2R antibody testing leads to a reduction in the frequency of investigations in MN patients.

Methods
Patients from three UK centres with a diagnosis of MN between 2009 and 2014 were identified. We compared patients who had a positive anti-PLA2R test within 6 months of biopsy with those who had no test or a negative test. Records were reviewed for investigations that took place 6 months prior to and 6 months following the biopsy date to see if these were normal or identified a secondary cause of MN.

Results
In total, 184 patients were included: 80 had no test, 66 had a negative anti-PLA2R test and 38 had a positive test within 6 months of diagnosis. In 2012, 46.5% of patients had an anti-PLA2R test, increasing to 93.3% in 2014. From 2012 to 2014 the number of screening tests dropped from 10.03 to 4.29 and the costs from £497.92 to £132.94.

Conclusions
Since its introduction, a progressively higher proportion of patients diagnosed with MN had an anti-PLA2R test. This has led to a reduction in the number of screening tests and in the cost of investigations carried out. The anti-PLA2R test has the potential to reduce this burden as its use becomes more widespread.
Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria
Authors: Ronneau Séverin , Hallez Régis 
Published: March 2019

ABSTRACTBacteria use dedicated mechanisms to respond adequately to fluctuating environments and to optimize their chances of survival in harsh conditions. One of the major stress responses used by virtually all bacteria relies on the sharp accumulation of an alarmone, the guanosine penta- or tetra-phosphate commonly referred to as (p)ppGpp. Under stressful conditions, essentially nutrient starvation, these second messengers completely reshape the metabolism and physiology by coordinately modulating growth, transcription, translation and cell cycle. As a central regulator of bacterial stress response, the alarmone is also involved in biofilm formation, virulence, antibiotics tolerance and resistance in many pathogenic bacteria. Intracellular concentrations of (p)ppGpp are determined by a highly conserved and widely distributed family of proteins called RelA-SpoT Homologs (RSH). Recently, several studies uncovering mechanisms that regulate RSH activities have renewed a strong interest in this field. In this review, we outline the diversity of the RSH protein family as well as the molecular devices used by bacteria to integrate and transform environmental cues into intracellular (p)ppGpp levels.
Genetic Variation in Acoustic Time of Flight and Drill Resistance of Juvenile Wood in a Large Loblolly Pine Breeding Population
Authors: Walker Trevor D , Isik Fikret , McKeand Steven E 
Published: March 2019

AbstractAcoustic time of flight and drill resistance (surrogates for wood stiffness and density, respectively) were measured on 11,097 standing trees from 269 pollen-mix families of loblolly pine (Pinus taeda L.) in 6- to 9-year-old progeny tests at eight sites across the southeastern United States. Specific gravity was measured on two test sites. The phenotypic correlation between specific gravity and drill resistance was moderate (r = 0.68), whereas the genetic correlation was very strong (rg = 0.96). Narrow-sense heritabilities for acoustic time of flight and drill resistance were around 0.35 for individual trees and very strong (0.90) for family means. High genetic correlations (&gt;0.80) between pairs of sites suggested a low genotype-by-environment interaction for both traits. Genetic correlations between wood quality traits and other economic traits (growth and stem straightness) were low except for a moderate correlation between acoustic time of flight and tree slenderness (rg = –0.64). The checklot ranked near the middle for both wood quality traits, implying no inadvertent selection occurred in this population that has been selected intensively for volume productivity. This study is the first to apply these tools in a large breeding program, and results suggest they are effective for selecting genotypes for wood quality.
Central Europe’s descent into autocracy: A constitutional analysis of authoritarian populism
Authors: Bugarič Bojan 
Published: March 2019

Abstract
The article offers an analysis of the particular type of populism that has evolved in Eastern and Central Europe, most notably in Hungary and Poland. The new populism in ECE differs from other populisms because it combines the elements of populism, ethnonationalism, and authoritarianism. Adhering to a similar script, which consists of sustained attacks on rule of law institutions, civil rights and freedoms, the media, and electoral rules, both populist governments in a relatively short period of time dismantled almost all the key cornerstones of democracy in Hungary and Poland. The current surge of populism in ECE demonstrates that constitutional democracy is in great danger when its core principles no longer enjoy wide democratic support. Paradoxically, constitutional democracy can play its “counter-majoritarian” role only when a majority of the people believe that it is the only game in town. Ultimately, democratic political parties and social movements with credible political ideas and programs offer the best hope for the survival of constitutional democracy. The role of law and constitutional checks and balances is less of an essential bulwark against democratic backsliding than is traditionally presumed in the legal literature.
Theoretical and practical motivations for the use of the moving average rule in the stock market
Authors: Kouaissah Noureddine , Orlandini Davide , Ortobelli Sergio , Tichý Tomas 
Published: March 2019

Abstract
This paper provides some theoretical foundations for using moving average (MA) rules in the stock market. In particular, the paper analyzes the conditional probability of price increments and examines how this probability varies over time. We prove under certain assumptions that the probability of being in an uptrend is greater than the probability of being in a downtrend. This demonstration partially justifies the common use of MA rules in the stock market. Finally, we propose an ex-post empirical analysis to evaluate and compare the performance of some MA rules and other portfolio strategies in the US stock market. In this context, we also suggest a methodology that incorporates these trading rules as alarm rules to predict potential market failures. Our ex-post results confirm the advantages of using these trading rules to predict market trends and crises.
Clinical impacts of administering a nonsteroidal anti-inflammatory drug to beef calves after assisted calving on pain and inflammation, passive immunity, health, and growth
Authors: Pearson Jennifer M , Pajor Edmond A , Campbell John R , Caulkett Nigel A , Levy Michel , Dorin Craig , Windeyer M Claire 
Published: March 2019

AbstractAssisted calves are often born weak, injured, or oxygen deprived and have a higher risk of morbidity and mortality. The objective was to investigate the impact of using pain mitigation at birth in assisted beef calves on physiological indicators of pain and inflammation, passive immunity, health, and growth. Thirty-three primiparous cows and their calves requiring assistance at birth on two ranches located in southern Alberta were enrolled. Data collected at birth include date and time of calving, calf sex, meconium staining, presentation of calf, and calving difficulty (easy assist: one person manually delivered the calf; difficult assist: delivery by two or more people, or mechanical assistance). Within 10 min of birth, calves were stratified by calving difficulty, randomized to a medication group, and received a subcutaneous dose of meloxicam (0.5 mg/kg BW) or an equivalent volume of placebo. Cow–calf pairs were then placed in individual box stalls for observation and sampling. At birth, 1, 4, and 24 h after birth, heart rate, respiratory rate, and rectal temperature were assessed and blood samples collected to measure indicators of pain and inflammation (cortisol, corticosterone, substance P, and haptoglobin). Serum IgG concentration and failed transfer of passive immunity (serum IgG concentration &lt;24 g/L) were assessed in the 24-h blood samples. Preweaning treatment for disease and mortality information was collected and calves were weighed at 7 to 10 d of age and at weaning. Of the 33 calves enrolled, 17 calves received meloxicam and 16 calves received a placebo. Meloxicam-medicated calves had significantly greater ADG to 7 to 10 d of age (P = 0.05) (mean = 0.9 kg/d; SE = 0.10) compared with placebo-medicated calves (mean = 0.6 kg/d; SE = 0.12). There was no significant effect of meloxicam on physiological indicators of pain and inflammation, standing or nursing by 1 h, passive immunity, health outcomes, or ADG to weaning (P &gt; 0.1). Although this was a small sample population, meloxicam given to assisted calves at birth improved ADG in the first week of life, which may indicate an important production management tool for improving well-being in assisted calves.
Contemporary Validation of a Nomogram Predicting Colon Cancer Recurrence, Revealing All-Stage Improved Outcomes
Authors: Konishi Tsuyoshi , Shimada Yoshifumi , Hsu Meier , Wei Iris H , Pappou Emmanouil , Smith J Joshua , Nash Garrett M , Guillem José G , Paty Philip B , Garcia-Aguilar Julio , Cercek Andrea , Yaeger Rona , Stadler Zsofia K , Segal Neil H , Varghese Anna , Saltz Leonard B , Shia Jinru , Vakiani Efsevia , Gönen Mithat , Weiser Martin R 
Published: March 2019

AbstractBackgroundThe Memorial Sloan Kettering Cancer Center (MSK) colon cancer recurrence nomogram is a risk calculator that provides patients and clinicians with individualized prediction of recurrence following curative resection of colon cancer. Although validated on multiple separate cohorts, the nomogram requires periodic updating as patient care changes over time. The aim of this study was to evaluate the nomogram’s accuracy in a contemporary cohort and modify the tool to reflect improvements in outcome related to advances in colon cancer therapy.MethodsA contemporary patient cohort was compiled, including consecutive colon cancer patients undergoing curative resection for stage I–III colon adenocarcinoma at MSK from 2007 to 2014. The nomogram’s predictive accuracy was assessed by concordance index and calibration plots of predicted vs actual freedom from recurrence at 5 years after surgery.ResultsData from a total of 999 eligible patients with complete records were used for validation. Median follow-up among survivors was 37 months. The concordance index was 0.756 (95% confidence interval = 0.707 to 0.805), indicating continued discriminating power, but the calibration plot revealed that the nomogram overestimated recurrence risk. Recalibration of the nomogram by estimating a new baseline freedom-from-recurrence function restored the nomogram’s accuracy.ConclusionThe updated nomogram retains the original nomogram’s variables but includes a lower baseline estimation of recurrence risk, reflecting improvements in outcomes for all stages of colon cancer, likely resulting from advances in imaging and integration of multiple treatment modalities.
Association Between Children’s Hospital Visitor Restrictions and Healthcare-Associated Viral Respiratory Infections: A Quasi-Experimental Study
Authors: Forkpa Hawa , Rupp Angela H , Shulman Stanford T , Patel Sameer J , Gray Elizabeth L , Zheng Xiaotian , Bovee Maria , Kociolek Larry K 
Published: March 2019

AbstractWe investigated the effect of annual winter visitor restrictions on hospital respiratory virus transmission. The healthcare-associated (HA) viral respiratory infection (VRI) transmission index (number of HA VRIs per 100 inpatient community-associated VRIs) was 59% lower during the months in which visitor restrictions were implemented. These data prompt consideration for instituting year-round visitor restrictions.
Maize glossy6 is involved in cuticular wax deposition and drought tolerance
Authors: Li Li , Du Yicong , He Cheng , Dietrich Charles R , Li Jiankun , Ma Xiaoli , Wang Rui , Liu Qiang , Liu Sanzhen , Wang Guoying , Schnable Patrick S , Zheng Jun 
Published: March 2019

AbstractCuticular waxes, long-chain hydrocarbon compounds, form the outermost layer of plant surfaces in most terrestrial plants. The presence of cuticular waxes protects plants from water loss and other environmental stresses. Cloning and characterization of genes involved in the regulation, biosynthesis, and extracellular transport of cuticular waxes onto the surface of epidermal cells have revealed the molecular basis of cuticular wax accumulation. However, intracellular trafficking of synthesized waxes to the plasma membrane for cellular secretion is poorly understood. Here, we characterized a maize glossy (gl6) mutant that exhibited decreased epicuticular wax load, increased cuticle permeability, and reduced seedling drought tolerance relative to wild-type. We combined an RNA-sequencing-based mapping approach (BSR-Seq) and chromosome walking to identify the gl6 candidate gene, which was confirmed via the analysis of multiple independent mutant alleles. The gl6 gene represents a novel maize glossy gene containing a conserved, but uncharacterized, DUF538 domain. This study suggests that the GL6 protein may be involved in the intracellular trafficking of cuticular waxes, opening the door to elucidating the poorly understood process by which cuticular wax is transported from its site of biosynthesis to the plasma membrane.
Prospective Investigation of an Automated PCR/Nucleic Acid Microarray-Based Platform for Enteric Pathogen Testing
Authors: Beckman Amy K , Ferrieri Patricia 
Published: March 2019

Abstract

Background
The Verigene Enteric Pathogens Test (Luminex Corporation) is a polymerase chain reaction (PCR)/nucleic acid microarray-based assay targeting 8 bacterial and viral pathogens that cause diarrhea.

Objective
To compare traditional enteric culture methods with stool testing by Verigene EP (PCR/microarray).

Methods
Tests were performed using PCR/microarray between February and August 2016. All specimens also underwent culture for Salmonella and Shigella; specimens that tested positive for bacterial pathogen(s) had confirmatory cultures.

Results
Valid results were obtained for 99.3% of the 3795 stool specimens. Among these, 497 (13.2%) specimens tested positive for at least 1 pathogen by PCR/microarray; 45.5% of these tested positive for 1 or more bacterial pathogens. Agreement between positive bacterial PCR/microarray results and culture-based testing was 85.3%. Compared with cultures, PCR/microarray demonstrated 95.2% and 87.5% sensitivity and 99.8% and 99.8% specificity for Salmonella and Shigella, respectively.

Conclusions
The Verigene EP generated evaluable results for most stool specimens tested and demonstrated good agreement with bacterial cultures.
EZHIP/CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma
Authors: Hübner Jens-Martin , Müller Torsten , Papageorgiou Dimitris N , Mauermann Monika , Krijgsveld Jeroen , Russell Robert B , Ellison David W , Pfister Stefan M , Pajtler Kristian W , Kool Marcel 
Published: March 2019

Abstract

Background
Posterior fossa A (PFA) ependymomas are one of 9 molecular groups of ependymoma. PFA tumors are mainly diagnosed in infants and young children, show a poor prognosis, and are characterized by a lack of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark. Recently, we reported overexpression of chromosome X open reading frame 67 (CXorf67) as a hallmark of PFA ependymoma and showed that CXorf67 can interact with enhancer of zeste homolog 2 (EZH2), thereby inhibiting polycomb repressive complex 2 (PRC2), but the mechanism of action remained unclear.

Methods
We performed mass spectrometry and peptide modeling analyses to identify the functional domain of CXorf67 responsible for binding and inhibition of EZH2. Our findings were validated by immunocytochemistry, western blot, and methyltransferase assays.

Results
We find that the inhibitory mechanism of CXorf67 is similar to diffuse midline gliomas harboring H3K27M mutations. A small, highly conserved peptide sequence located in the C-terminal region of CXorf67 mimics the sequence of K27M mutated histones and binds to the SET domain (Su(var)3-9/enhancer-of-zeste/trithorax) of EZH2. This interaction blocks EZH2 methyltransferase activity and inhibits PRC2 function, causing de-repression of PRC2 target genes, including genes involved in neurodevelopment.

Conclusions
Expression of CXorf67 is an oncogenic mechanism that drives H3K27 hypomethylation in PFA tumors by mimicking K27M mutated histones. Disrupting the interaction between CXorf67 and EZH2 may serve as a novel targeted therapy for PFA tumors but also for other tumors that overexpress CXorf67. Based on its function, we have renamed CXorf67 as “EZH Inhibitory Protein” (EZHIP).
Shallow Equality and Symbolic Jurisprudence in Multilingual Legal Orders
Authors: Leung Janny H.C. 
Published: March 2019

Abstract
This book offers a critical perspective to the proliferation of official multilingualism in the contemporary world. Through diachronic and synchronic comparisons, it shows that official multilingualism has become a norm in the political management of linguistic diversity, but actual practices vary according to sociohistorical contexts and current power dynamics. It explains such convergences and divergences using a theory of symbolic jurisprudence, which posits that official language law has served chiefly as a discursive resource for a range of political and economic functions, such as ensuring stability, establishing legitimacy, balancing rival powers, and harnessing trade opportunities. The book goes on to examine the practical impact of official multilingualism on public institutions and legal processes and the application of linguistic equality—frequently asserted in multilingual polities—on the ground. The study shows that serious pursuit of linguistic equality calls for elaborate administrative effort in public institutions and carries a potential to clash with existing legal practices (from legal drafting and interpretation, to language rights in trial proceedings). However, such changes—however extensive—hardly ever disrupt the status quo. The book further argues that linguistic equality as proclaimed and practiced in many polities today is shallow in character, and must not be confused with popular conceptions of equality. The book concludes that both symbolic jurisprudence and shallow equality are components of a policy of strategic pluralism that underlies official multilingualism. Although official multilingualism can legitimately be used to pursue collective goals, it runs the underlying risks of disguising substantive inequalities and displacing more progressive efforts in social change.
Tracing Linguistic Management through Time
Authors: Leung Janny H.C. 
Published: March 2019

Abstract
This chapter offers a historical account of how polities have operated in a linguistically diverse society. Although societal multilingualism has been commonplace throughout human civilization, official multilingualism is clearly a modern phenomenon. However, whether the use of a language is mandated by policy or law, or is a matter of convention, polities have always had to deal with linguistic diversity. Therefore, instead of comparing the language(s) that receive official recognition, the chapter uses law as a site to examine the internal language practice of a polity in different historical periods. The account shows that official multilingualism today, encapsulating contemporary ethics and politics, has characteristics that distinguish it from treaded paths of linguistic management.
How Official Multilingualism Works
Authors: Leung Janny H.C. 
Published: March 2019

Abstract
This chapter spells out major sociopolitical forces that have contributed to the widespread adoption of official multilingualism, and offers an explanation of how official multilingualism works through law. Jurisdictions that adopt multilingual law are primarily driven by pragmatic rather than normative forces. Official language law can perform a plethora of instrumental functions because such law works chiefly through its symbolic power. This discursive reading of law is contrary to the dominant, positivist view of law as command of a sovereign backed by force. Although symbolism is sometimes defined in opposition to what is real or substantive, law that works through symbolism is not necessarily empty in content or limited in impact. In fact, its semiotic flexibility has allowed it to be used to pursue a wide range of instrumental goals, which consist mostly of political and economic capital.