bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paclitaxel mitigates structural alterations and cardiac conduction system defects in a mouse model of Hutchinson–Gilford progeria syndrome
Authors: Macías Álvaro , Díaz-Larrosa J Jaime , Blanco Yaazan , Fanjul Víctor , González-Gómez Cristina , Gonzalo Pilar , Andrés-Manzano María Jesús , da Rocha Andre Monteiro , Ponce-Balbuena Daniela , Allan Andrew , Filgueiras-Rama David , Jalife José , Andrés Vicente 
Published: February 2021

AbstractAimsHutchinson–Gilford progeria syndrome (HGPS) is an ultrarare laminopathy caused by expression of progerin, a lamin A variant, also present at low levels in non-HGPS individuals. HGPS patients age and die prematurely, predominantly from cardiovascular complications. Progerin-induced cardiac repolarization defects have been described previously, although the underlying mechanisms are unknown.Methods and resultsWe conducted studies in heart tissue from progerin-expressing LmnaG609G/G609G (G609G) mice, including microscopy, intracellular calcium dynamics, patch-clamping, in vivo magnetic resonance imaging, and electrocardiography. G609G mouse cardiomyocytes showed tubulin-cytoskeleton disorganization, t-tubular system disruption, sarcomere shortening, altered excitation–contraction coupling, and reductions in ventricular thickening and cardiac index. G609G mice exhibited severe bradycardia, and significant alterations of atrio-ventricular conduction and repolarization. Most importantly, 50% of G609G mice had altered heart rate variability, and sinoatrial block, both significant signs of premature cardiac aging. G609G cardiomyocytes had electrophysiological alterations, which resulted in an elevated action potential plateau and early afterdepolarization bursting, reflecting slower sodium current inactivation and long Ca+2 transient duration, which may also help explain the mild QT prolongation in some HGPS patients. Chronic treatment with low-dose paclitaxel ameliorated structural and functional alterations in G609G hearts.ConclusionsOur results demonstrate that tubulin-cytoskeleton disorganization in progerin-expressing cardiomyocytes causes structural, cardiac conduction, and excitation–contraction coupling defects, all of which can be partially corrected by chronic treatment with low dose paclitaxel.
Climate change, weather shocks, and price convergence in pre-industrial Germany
Authors: Albers Hakon , Pfister Ulrich 
Published: February 2021

Abstract
Market integration of European inland regions such as Germany caught up on North-Western Europe from the seventeenth century onwards. As many studies rely on grain prices and the pre-industrial era was a period of climate change, a relevant question is in how far changing weather shocks impact on the measurement of convergence trends. We create a new high-quality grain price dataset and apply four methodologies to quantify market integration robust to weather shocks and climate change. Population growth and river transport turn out as plausible explanations for price convergence rather than climate change.
Complex pleiotropic genetic architecture of evolved heat stress and oxidative stress resistance in the nematodeCaenorhabditis remanei
Authors: O’Connor Christine H , Sikkink Kristin L , Nelson Thomas C , Fierst Janna L , Cresko William A , Phillips Patrick C 
Published: February 2021

AbstractThe adaptation of complex organisms to changing environments has been a central question in evolutionary quantitative genetics since its inception. The structure of the genotype–phenotype maps is critical because pleiotropic effects can generate widespread correlated responses to selection and potentially restrict the extent of evolutionary change. In this study, we use experimental evolution to dissect the genetic architecture of natural variation for acute heat stress and oxidative stress response in the nematode Caenorhabiditis remanei. Previous work in the classic model nematode Caenorhabiditis elegans has found that abiotic stress response is controlled by a handful of genes of major effect and that mutations in any one of these genes can have widespread pleiotropic effects on multiple stress response traits. Here, we find that acute heat stress response and acute oxidative response in C. remanei are polygenic, complex traits, with hundreds of genomic regions responding to selection. In contrast to expectation from mutation studies, we find that evolved acute heat stress and acute oxidative stress response for the most part display independent genetic bases. This lack of correlation is reflected at the levels of phenotype, gene expression, and in the genomic response to selection. Thus, while these findings support the general view that rapid adaptation can be generated by changes at hundreds to thousands of sites in the genome, the architecture of segregating variation is likely to be determined by the pleiotropic structure of the underlying genetic networks.
Selection into shift work is influenced by educational attainment and body mass index: a Mendelian randomization study in the UK Biobank
Authors: Daghlas Iyas , Richmond Rebecca C , Lane Jacqueline M , Dashti Hassan S , Ollila Hanna M , Schernhammer Eva S , Smith George Davey , Rutter Martin K , Saxena Richa , Vetter Céline 
Published: February 2021

AbstractBackgroundShift work is associated with increased cardiometabolic disease risk. This observation may be partly explained by cardiometabolic risk factors having a role in the selection of individuals into or out of shift work. We performed Mendelian randomization (MR) analyses in the UK Biobank (UKB) to test this hypothesis.MethodsWe used genetic risk scores (GRS) to proxy nine cardiometabolic risk factors and diseases (including educational attainment, body mass index (BMI), smoking, and alcohol consumption), and tested associations of each GRS with self-reported frequency of current shift work among employed UKB participants of European ancestry (n = 190 573). We used summary-level MR sensitivity analyses to assess robustness of the identified effects, and we tested whether effects were mediated through sleep timing preference.ResultsGenetically instrumented liability to lower educational attainment (odds ratio (OR) per 3.6 fewer years in educational attainment = 2.40, 95% confidence interval (CI) = 2.22–2.59, P = 4.84 × 10–20) and higher body mass index (OR per 4.7 kg/m2 higher BMI = 1.30, 95% CI = 1.14–1.47, P = 5.85 × 10–5) increased odds of reporting participation in frequent shift work. Results were unchanged in sensitivity analyses allowing for different assumptions regarding horizontal pleiotropy. No selection effects were evident for the remaining exposures, nor for any exposures on selection out of shift work. Sleep timing preference did not mediate the effects of BMI and educational attainment on selection into shift work.ConclusionsLiability to lower educational attainment and higher BMI may influence selection into shift work. This phenomenon may bias epidemiological studies of shift work that are performed in the UKB.
Hamiltonian Floer Theory for Nonlinear Schrödinger Equations and the Small Divisor Problem
Authors: Fabert Oliver 
Published: February 2021

Abstract
We prove the existence of infinitely many time-periodic solutions of nonlinear Schrödinger equations using pseudo-holomorphic curve methods from Hamiltonian Floer theory. For the generalization of the Gromov–Floer compactness theorem to infinite dimensions, we show how to solve the arising small divisor problem by combining elliptic methods with results from the theory of diophantine approximations.
Role of the PhoPQ two-component regulatory system in the β-lactam resistance ofStenotrophomonas maltophilia
Authors: Huang Hsin-Hui , Wu Bo-Kuan , Li Li-Hua , Lin Yi-Tsung , Yang Tsuey-Ching 
Published: February 2021

AbstractBackgroundStenotrophomonas maltophilia, an opportunistic pathogen, is intrinsically resistant to most β-lactams except ceftazidime and ticarcillin/clavulanate, due to the inducibly expressed L1 and L2 β-lactamases. A two-component regulatory system (TCS) allows organisms to sense and respond to changes in different environmental conditions. The PhoPQ TCS of S. maltophilia plays regulatory roles in antibiotic susceptibility, physiology, stress adaption and virulence. Inactivation of S. maltophilia phoPQ increases β-lactam susceptibility.ObjectivesTo elucidate the PhoPQ-regulating mechanism for β-lactam resistance.MethodsThe candidate genes responsible for the ΔphoPQ-mediated β-lactam resistance compromise were identified by transcriptome analysis and verified by quantitative RT–PCR and complementation assay. Etest was used to assess β-lactam susceptibility. The phosphorylation level of the PhoP protein was determined by Phos-tag SDS-PAGE and western blotting. A β-lactam influx assay was used to investigate the influx efficiency of a β-lactam.ResultsPhoPQ deletion down-regulated the expression of mltD1 and slt, attenuated the induced β-lactamase activity and then compromised the β-lactam resistance. Complementation of mutant phoPQ with mltD1 or slt genes partially reverted the induced β-lactamase activity and β-lactam resistance. The PhoPQ TCS was activated in logarithmically grown KJ cells and was further activated by low magnesium, but not by a β-lactam. However, low-magnesium-mediated PhoPQ activation hardly made an impact on β-lactam resistance enhancement. Furthermore, PhoPQ inactivation altered the outer membrane permeability and increased the influx of a β-lactam.ConclusionsThe PhoPQ TCS is activated to some extent in physiologically grown S. maltophilia. Inactivation of phoPQ attenuates the expression of mltD1 and slt, and increases β-lactam influx, both synergically contributing to β-lactam resistance compromise.
Utility of 30-Day Readmission Metrics in the Burn Population: Navigating Quality Metric Limitations in Special Populations
Authors: Prindeze Nicholas J , Shupp Jeffrey W , Johnson Laura S 
Published: February 2021

Abstract
Hospital readmission data may be a useful tool in identifying risk factors leading to higher costs of care or poorer overall outcomes. Several studies have emerged utilizing these datasets to examine the trauma and burn population, which have been unable to distinguish planned from unplanned readmissions. The 2014 Nationwide Readmissions Database was queried for 363 burn-specific ICD-9 DX codes and filtered by age and readmission status to capture the adult burn population. Additionally, burn-related excision and grafting procedures were filtered from 25 ICD-9 SG codes to distinguish planned readmissions. A total of 26,719 burn patients were identified with 781 all-cause unscheduled 30-day readmissions. Further filtering by burn-related excision and grafting procedures then identified 468 patients undergoing a burn-related excision and grafting procedure on readmission, reducing the dataset to 313 patients and identifying up to 60% of readmissions as possibly improperly coded planned readmissions. From this dataset, nonoperative management on initial admission was found to have the strongest correlation with readmission (OR 5.00; 3.33–7.14). Notably corrected data, when stratified by annual burn patient admission volume, identified a significant likelihood of readmission (OR 4.57; 2.15–9.70) of centers receiving the lowest annual number of burn patients, which was not identified in the unfiltered dataset. Healthcare performance statistics may be a powerful metric when utilized appropriately; however, these databases must be carefully applied to small and special populations. This study has determined that as many as 60% of burn patient readmissions included in prior studies may be improperly coded planned readmissions.
Gastroduodenal amyloidosis: a case report and review of literature
Authors: Almushait Youssef B , Syed Faaezuddin , Abbasi Safwan U , Alhussaini Hussah F , Alsohaibani Fahad I 
Published: February 2021

Abstract
Amyloidosis is a disorder characterized by deposition of abnormally folded proteins in the extracellular space of various tissues and organs, possibly leading to their dysfunction. In the majority of cases, amyloidosis presents with systemic involvement including the gastrointestinal tract; however, localized gastroduodenal amyloidosis is rare. We report a case of gastroduodenal amyloidosis in a 36-year-old male with multiple comorbidities who presented with right upper quadrant abdominal pain. Reports of gastroduodenal amyloidosis and other relevant literature were also reviewed and discussed alongside this case.
Phloem loading in rice leaves depends strongly on the apoplastic pathway
Authors: Wang Gaopeng , Wu Yue , Ma Li , Lin Yan , Hu Yuxiang , Li Mengzhu , Li Weiwei , Ding Yanfeng , Chen Lin 
Published: February 2021

Abstract
Phloem loading is the first step in sucrose transport from source leaves to sink organs. The phloem loading strategy in rice remains unclear. To determine the potential phloem loading mechanism in rice, yeast invertase (INV) was overexpressed by a 35S promoter specifically in the cell wall to block sugar transmembrane loading in rice. The transgenic lines exhibited obvious phloem loading suppression characteristics accompanied by the accumulation of sucrose and starch, restricted vegetative growth and decreased grain yields. The decreased sucrose exudation rate with p-chloromercuribenzenesulfonic acid (PCMBS) treatment also indicated that rice actively transported sucrose into the phloem. OsSUT1 (SUCROSE TRANSPORTER 1) showed the highest mRNA levels of the plasma membrane-localized OsSUTs in source leaves. Cross sections of the OsSUT::GUS transgenic plants showed that the expression of OsSUT1 and OsSUT5 occurred in the phloem companion cells. Rice ossut1 mutants showed reduced growth and grain yield, supporting the hypothesis of OsSUT1 acting in phloem loading. Based on these results, we conclude that apoplastic phloem loading plays a major role in the export of sugar from rice leaves.
Auxin and gibberellin signaling cross-talk promotes hypocotyl xylem expansion and cambium homeostasis
Authors: Ben-Targem Mehdi , Ripper Dagmar , Bayer Martin , Ragni Laura 
Published: February 2021

Abstract
During secondary growth, the thickening of plant organs, wood (xylem) and bast (phloem) is continuously produced by the vascular cambium. In Arabidopsis hypocotyl and root, we can distinguish two phases of secondary growth based on cell morphology and production rate. The first phase, in which xylem and phloem are equally produced, precedes the xylem expansion phase in which xylem formation is enhanced and xylem fibers differentiate. It is known that gibberellins (GA) trigger this developmental transition via degradation of DELLA proteins and that the cambium master regulator BREVIPEDICELLUS/KNAT1 (BP/KNAT1) and receptor like kinases ERECTA and ERL1 regulate this process downstream of GA. However, our understanding of the regulatory network underlying GA-mediated secondary growth is still limited. Here, we demonstrate that DELLA-mediated xylem expansion in Arabidopsis hypocotyl is mainly achieved through DELLA family members RGA and GAI, which promote cambium senescence. We further show that AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8, which physically interact with DELLAs, specifically repress phloem proliferation and induce cambium senescence during the xylem expansion phase. Moreover, the inactivation of BP in arf6 arf8 background revealed an essential role for ARF6 and ARF8 in cambium establishment and maintenance. Overall, our results shed light on a pivotal hormone cross-talk between GA and auxin in the context of plant secondary growth.
MALDI-TOF-MS Analysis in the Discovery and Identification of the Serum Peptide Pattern of Pancreatic Ductal Adenocarcinoma
Authors: Huang Yuan , Chen Feng , Zhang Linglin , Lv Qian , Yan Jun , Cui Wei 
Published: February 2021

Abstract

Objective
To explore the application of serum peptidomics in the early diagnosis of pancreatic ductal adenocarcinoma (PDAC).

Methods
The serum specimens from 176 patients with PDAC and 158 healthy control patients were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry to obtain serum peptide profiles. Next, a classification model by differentiated peptides was established and verified to distinguish the 2 groups. Finally, the peptides were identified by tandem mass spectrometry.

Results
A classification model was established by 13 peptides. For patients with PDAC in the early stage, the sensitivity and specificity of the model reached 100% and 96.7%, respectively. The amino acid sequences of the 13 peptides were then determined and the types of proteins were identified, including platelet basic protein, fibrinogen alpha, complement C3, and secreted frizzled-related protein 4. Some of the 13 peptides could be potential PDAC biomarkers.

Conclusion
Serum peptidomics may have potential application in the early diagnosis of PDAC.
Understanding the Middle East through the eyes of Japan’s Newspapers: A topic modelling and sentiment analysis approach
Authors: Ghasiya Piyush , Okamura Koji 
Published: February 2021

Abstract
For Japan—a country that has always been described with virtually no major natural resources such as oil, gas, and coal—the Middle Eastern region has a special place in its economic and foreign policy. In 2017, 39% of Japan’s energy came from oil, and 87% of Japan’s imported oil came from the Middle East, predominantly Saudi Arabia and the UAE. The above facts are enough to discern the critical significance of the Middle Eastern region for Japan. For Japan to have an unhindered supply of oil and other natural resources, it is pertinent that this region remains peaceful. In this scenario, the Middle East-related articles in Japan’s newspapers can help understand Japan’s perspective towards the Middle East. This paper would first apply the topic modelling approach non-negative matrix factorization (NMF) on Middle East-related articles from three newspapers of Japan. After discovering crucial topics, we would utilize traditional supervised machine learning algorithms to determine the overall and topic-specific sentiments from the collected headlines. Our topic modelling results discovered that the Japanese media widely reported issues like Islamic State, the refugee crisis, the Syrian civil war, Qasem Soleimani killing, and Iran nuclear deal. Further, the news related to Saudi Arabia, Syria, and Trump garnered high negative sentiment.
Richness, abundance and spatial heterogeneity of gastropods and bivalves in coral ecosystems across the Mexican Tropical Pacific
Authors: Barrientos-Luján Norma Arcelia , Rodríguez-Zaragoza Fabián Alejandro , López-Pérez Andrés 
Published: February 2021

ABSTRACT
The diversity of gastropods and bivalves, total mollusc richness and total mollusc abundance were analysed for three substrates (coral, rock and sand) in the coral and reef ecosystems of the Mexican Tropical Pacific (MTP). Up to 3,828 individuals (70% gastropods and 30% bivalves), belonging to 209 species (146 gastropods and 63 bivalves), were identified; this is one of the most diverse molluscan faunas (2.77 species/m2) associated with reef systems in the MTP. Evaluation of the sampling effort demonstrated that 80% of gastropod species and 93% of bivalve species inhabiting the reef system were recovered. The highest abundance occurred in the coral substrate (1,939 individuals), while the highest species richness was found on the rock substrate (131 species). The analysis showed that the greatest spatial variation in total mollusc, gastropod and bivalve diversity occurred among different substrates within individual localities, with minor differences among assemblages with increasing spatial scale reflecting the relative homogeneity of the molluscan fauna in the study area. While the gastropods Conus nux, Steironepion piperatum and Muricopsis zeteki accounted for differences among different regions, and Vermicularia pellucida eburnea and Bostrycapulus aculeatus accounted for differences among states, the abundances of M. zeteki, B. aculeatus and V. pellucida eburnea were related to differences in diversity at the scale of individual localities. Among bivalves, Leiosolenus aristatus, L. plumula and Gastrochaena ovata accounted for differences between regions, states and localities, respectively. Overall, the study shows that species composition is influenced by both the substrate and the geographical location of assemblages. This indicates that conservation strategies should address preserving habitat heterogeneity at local scales in the study area.
Frustrated folding of guanine quadruplexes in telomeric DNA
Authors: Carrino Simone , Hennecker Christopher D , Murrieta Ana C , Mittermaier Anthony 
Published: February 2021

AbstractHuman chromosomes terminate in long, single-stranded, DNA overhangs of the repetitive sequence (TTAGGG)n. Sets of four adjacent TTAGGG repeats can fold into guanine quadruplexes (GQ), four-stranded structures that are implicated in telomere maintenance and cell immortalization and are targets in cancer therapy. Isolated GQs have been studied in detail, however much less is known about folding in long repeat sequences. Such chains adopt an enormous number of configurations containing various arrangements of GQs and unfolded gaps, leading to a highly frustrated energy landscape. To better understand this phenomenon, we used mutagenesis, thermal melting, and global analysis to determine stability, kinetic, and cooperativity parameters for GQ folding within chains containing 8–12 TTAGGG repeats. We then used these parameters to simulate the folding of 32-repeat chains, more representative of intact telomeres. We found that a combination of folding frustration and negative cooperativity between adjacent GQs increases TTAGGG unfolding by up to 40-fold, providing an abundance of unfolded gaps that are potential binding sites for telomeric proteins. This effect was most pronounced at the chain termini, which could promote telomere extension by telomerase. We conclude that folding frustration is an important and largely overlooked factor controlling the structure of telomeric DNA.
The origin and development of firm management
Authors: Giorcelli Michela 
Published: February 2021

Abstract
This paper examines the historical origin and diffusion of management practices. Despite their centrality in modern world, the concepts of ‘management’ developed fairly recently. Only with the Industrial Revolution, due to the increased firm size, owners needed a management structure to coordinate activities across different plants. Management soon became the subject of numerous studies in economics, sociology, and psychology to maximize firm productivity. The first large-scale programme of management practices diffusion was developed in the US during the Second World War: offering such training to US firms involved in war production boosted their performance for at least 10 years. After the Second World War, the US exported its management principles to Europe, where they have large and persistent effects on small firm productivity, and to Japan, where they interacted with the local economic conditions and originated the ‘kaizen Japanese management’, which aims at ‘continuous improvement’ in firm performance.