bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of givosiran for acute hepatic porphyria: 24‐month interim analysis of the randomized phase 3 ENVISION study
Authors: Ventura Paolo , Bonkovsky Herbert L. , Gouya Laurent , Aguilera‐Peiró Paula , Montgomery Bissell D. , Stein Penelope E. , Balwani Manisha , Anderson D. Karl E. , Parker Charles , Kuter David J. , Monroy Susana , Oh Jeeyoung , Ritchie Bruce , Ko John J. , Hua Zhaowei , Sweetser Marianne T. , Sardh Eliane ,   for the ENVISION Investigators
Published: October 2021

AbstractBackground & AimsUpregulation of hepatic delta‐aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta‐aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims: evaluate long‐term efficacy and safety of givosiran in acute hepatic porphyria.MethodsInterim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double‐blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open‐label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta‐aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events.ResultsPatients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double‐blind period, 0.0 in open‐label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double‐blind period) and 0.0 (open‐label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long‐term givosiran led to sustained lowering of delta‐aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double‐blind period.ConclusionsLong‐term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life.
Seasonal genotype dynamics of a marine dinoflagellate: Pelagic populations are homogeneous and as diverse as benthic seed banks
Authors: Jerney Jacqueline , Rengefors Karin , Nagai Satoshi , Krock Bernd , Sjöqvist Conny , Suikkanen Sanna , Kremp Anke 
Published: October 2021

AbstractGenetic diversity is the basis for evolutionary adaptation and selection under changing environmental conditions. Phytoplankton populations are genotypically diverse, can become genetically differentiated within small spatiotemporal scales and many species form resting stages. Resting stage accumulations in sediments (seed banks) are expected to serve as reservoirs for genetic information, but so far their role in maintaining phytoplankton diversity and in evolution has remained unclear. In this study we used the toxic dinoflagellate Alexandrium ostenfeldii (Dinophyceae) as a model organism to investigate if (i) the benthic seed bank is more diverse than the pelagic population and (ii) the pelagic population is seasonally differentiated. Resting stages (benthic) and plankton (pelagic) samples were collected at a coastal bloom site in the Baltic Sea, followed by cell isolation and genotyping using microsatellite markers (MS) and restriction site associated DNA sequencing (RAD). High clonal diversity (98%–100%) combined with intermediate to low gene diversity (0.58–0.03, depending on the marker) was found. Surprisingly, the benthic and pelagic fractions of the population were equally diverse, and the pelagic fraction was temporally homogeneous, despite seasonal fluctuation of environmental selection pressures. The results of this study suggest that continuous benthic–pelagic coupling, combined with frequent sexual reproduction, as indicated by persistent linkage equilibrium, prevent the dominance of single clonal lineages in a dynamic environment. Both processes harmonize the pelagic with the benthic population and thus prevent seasonal population differentiation. At the same time, frequent sexual reproduction and benthic–pelagic coupling maintain high clonal diversity in both habitats.
Isoprene enhances leaf cytokinin metabolism and induces early senescence
Authors: Dani Kaidala Ganesha Srikanta , Pollastri Susanna , Pinosio Sara , Reichelt Michael , Sharkey Thomas D. , Schnitzler Jörg‐Peter , Loreto Francesco 
Published: October 2021

Summary

Isoprene, a major biogenic volatile hydrocarbon of climate‐relevance, indisputably mitigates abiotic stresses in emitting plants. However functional relevance of constitutive isoprene emission in unstressed plants remains contested. Isoprene and cytokinins (CKs) are synthesized from a common substrate and pathway in chloroplasts. It was postulated that isoprene emission may affect CK‐metabolism.

Using transgenic isoprene‐emitting (IE) Arabidopsis and isoprene nonemitting (NE) RNA‐interference grey poplars (paired with respective NE and IE genotypes), the life of individual IE and NE leaves from emergence to abscission was followed under stress‐free conditions. We monitored plant growth rate, aboveground developmental phenotype, modelled leaf photosynthetic energy status, quantified the abundance of leaf CKs, analysed Arabidopsis and poplar leaf transcriptomes by RNA‐sequencing in presence and absence of isoprene during leaf senescence.

Isoprene emission by unstressed leaves enhanced the abundance of CKs (isopentenyl adenine and its precursor) by > 200%, significantly upregulated genes coding for CK‐synthesis, CK‐signalling and CK‐degradation, hastened plant development, increased chloroplast metabolic rate, altered photosynthetic energy status, induced early leaf senescence in both Arabidopsis and poplar. IE leaves senesced sooner even in decapitated poplars where source–sink relationships and hormone homeostasis were perturbed.

Constitutive isoprene emission significantly accelerates CK‐led leaf and organismal development and induces early senescence independent of growth constraints. Isoprene emission provides an early‐riser evolutionary advantage and shortens lifecycle duration to assist rapid diversification in unstressed emitters.
Non‐pharmacological interventions for pollen‐induced allergic symptoms: Systematic literature review
Authors: Schutzmeier Paul , Kutzora Susanne , Mittermeier Isabella , Becker Jana , Bergmann Karl‐Christian , Böse‐O’Reilly Stephan , Buters Jeroen , Damialis Athanasios , Heinrich Joachim , Kabesch Michael , Mertes Hanna , Nowak Dennis , Korbely Christine , Walser‐Reichenbach Sandra , Weinberger Alisa , Heinze Stefanie , Steckling‐Muschack Nadine , Herr Caroline 
Published: October 2021

AbstractBackgroundAllergic diseases pose a health problem worldwide. Pollen are widespread aeroallergens which can cause symptoms like shortness of breath, cough, itchy eyes, or rhinitis. Apart from preventive measures and pharmacological treatment, also non‐pharmacological interventions have been suggested to reduce symptoms. The objective of this work was to review studies investigating the effectiveness of non‐pharmacologic interventions to reduce allergic symptoms.MethodsPubMed, EMBASE, and CENTRAL were systematically reviewed in July 2018 and April 2020. Several authors worked on the screening of titles, abstracts, and full texts. One author for each literature search performed the data extraction and the risk of bias assessment. Studies were included if they met the inclusion criteria defined by the PECOs. Studies which investigating the effect of non‐pharmacologic interventions on patients with allergic rhinitis were included.ResultsTwenty‐nine studies investigating eleven types of non‐pharmacologic interventions to avoid and reduce allergic symptoms due to pollen exposure were included in this review. Out of all studies, seven studies addressed nasal rinsing and 22 included acupuncture, air filtering, artisanal tears, individual allergen avoidance advice, various nasal applications, self‐hypnosis, rhinophototherapy, and wraparound sunglasses.ConclusionMost studies had a high risk of bias and small sample sizes. There were only a few high‐quality studies that give hints about the effectiveness of non‐pharmacological interventions. For future research, more high‐quality studies are required to confirm the effectiveness of simple, safe, and cost‐effective interventions.
Genome and systems biology of Melilotus albus provides insights into coumarins biosynthesis
Authors: Wu Fan , Duan Zhen , Xu Pan , Yan Qi , Meng Minghui , Cao Mingshu , Jones Chris S. , Zong Xifang , Zhou Pei , Wang Yimeng , Luo Kai , Wang Shengsheng , Yan Zhuanzhuan , Wang Penglei , Di Hongyan , Ouyang Zifeng , Wang Yanrong , Zhang Jiyu 
Published: October 2021

SummaryMelilotus species are used as green manure and rotation crops worldwide and contain abundant pharmacologically active coumarins. However, there is a paucity of information on its genome and coumarin production and function. Here, we reported a chromosome‐scale assembly of Melilotus albus genome with 1.04 Gb in eight chromosomes, containing 71.42% repetitive elements. Long terminal repeat retrotransposon bursts coincided with declining of population sizes during the Quaternary glaciation. Resequencing of 94 accessions enabled insights into genetic diversity, population structure, and introgression. Melilotus officinalis had relatively larger genetic diversity than that of M. albus. The introgression existed between M. officinalis group and M. albus group, and gene flows was from M. albus to M. officinalis. Selection sweep analysis identified candidate genes associated with flower colour and coumarin biosynthesis. Combining genomics, BSA, transcriptomics, metabolomics, and biochemistry, we identified a β‐glucosidase (BGLU) gene cluster contributing to coumarin biosynthesis. MaBGLU1 function was verified by overexpression in M. albus, heterologous expression in Escherichia coli, and substrate feeding, revealing its role in scopoletin (coumarin derivative) production and showing that nonsynonymous variation drives BGLU enzyme activity divergence in Melilotus. Our work will accelerate the understanding of biologically active coumarins and their biosynthetic pathways, and contribute to genomics‐enabled Melilotus breeding.
In vitro activity of isothiocyanates against Fusarium graminearum
Authors: Ashiq Samina , Edwards Simon G. , Fatukasi Olajide , Watson Andrew , Back Matthew A. 
Published: October 2021

AbstractIsothiocyanates are biotoxic degradation products formed as a result of enzymatic hydrolysis of glucosinolates present in Brassica species. The application of biofumigant Brassica crops, as an alternative crop protection method for soilborne pathogens and pests is increasingly gaining interest. However, little is known of the potential of biofumigation to reduce the inoculum of Fusarium species affecting cereals. The aim of this study was to evaluate the antifungal activity of five isothiocyanates, namely allyl, benzyl, ethyl, 2‐phenylethyl and methyl isothiocyanates, against germination and growth of Fusarium graminearum under in vitro conditions. Aromatic isothiocyanates were more inhibitory than the aliphatic isothiocyanates against mycelial growth, whereas the reverse was observed for conidial germination. Among the tested isothiocyanates, allyl and methyl isothiocyanates were more efficient overall, showing lower ED50 values (35–150 mg/L) for conidial germination and mycelial radial growth. The findings suggest that Brassica plants containing allyl and methyl glucosinolates could have a suppressive effect, reducing the inoculum of F. graminearum in soil prior to cereal production.
Characterization and proteomics of chicken seminal plasma extracellular vesicles
Authors: Luo Xuliang , Guo Yan , Huang Ying , Cheng Manman , Wu Xiaohui , Gong Yanzhang 
Published: October 2021

AbstractIn mammals, seminal plasma extracellular vesicles (SPEVs) can regulate sperm motility and capacitation. The characteristics and functions of SPEVs in avians have been rarely reported. In this study, chicken SPEVs were isolated and characterized by transmission and scanning electron microscopy (TEM/SEM) and nanoparticle tracking analysis (NTA); furthermore, seven extracellular vesicle (EVs) marker proteins were detected by Western blot (WB). TEM revealed that chicken SPEVs had a classic bilayer membrane structure. NTA confirmed that the size of SPEVs was 30–250 nm, and concentration ranged from 8.0 E + 11–8.5 E + 11 particles/ml. There were 3073 SPEVs proteins identified by deep sequencing, including 2794 intracellular proteins and 279 extracellular proteins. The overlap rate of proteomes between chicken SPEVs and vesicles reported in the Vesiclepedia database reached 86%, and 360 new proteins that had not been reported by the ExoCarta and Vesiclepedia databases were identified in chicken SPEV proteomes. Gene Ontology (GO) analysis revealed that chicken SPEV proteins were mainly enriched in supplying energy and transporting protein. There were 4 IFT family proteins speculated to play an important role in sperm composition and function. Our data were compared with two previously published studies on the proteomics of chicken seminal plasma (SP) and hen uterine fluid, and some overlapping proteins described in chicken SPEVs had been identified in hen uterine fluid (545) and chicken SP (284). In conclusion, these findings will increase our understanding of the content and composition of proteome in SPEVs and provide new insights into the important role of the SPEV regulation in sperm functions.
Genomic diversity and resistome profiles of Salmonella enterica subsp. enterica serovar Kentucky isolated from food and animal sources in Ireland
Authors: Slowey Rosemarie , Kim Seon Woo , Prendergast Deirdre , Madigan Gillian , Van Kessel Jo Ann S. , Haley Bradd J. 
Published: October 2021

AbstractSalmonella enterica subsp. enterica serovar Kentucky is frequently isolated from poultry, dairy and beef cattle, the environment and people with clinical salmonellosis globally. However, the sources of this serovar and its diversity and antimicrobial resistance capacities remain poorly described in many regions. To further understand the genetic diversity and antimicrobial sensitivity patterns among S. Kentucky strains isolated from non‐human sources in Ireland, we sequenced and analysed the genomes of 61 isolates collected from avian, bovine, canine, ovine, piscine, porcine, environmental and vegetation sources between 2000 and 2016. The majority of isolates (n = 57, 93%) were sequence type (ST) 314, while only three isolates were ST198 and one was ST152. Several isolates were multidrug‐resistant (MDR) and 14 carried at least one acquired antimicrobial resistance gene. When compared to a database of publicly available ST314, four distinct clades were identified (clades I–IV), with the majority of isolates from Ireland clustering together in Clade I. Two of the three ST198 isolates were characteristic of those originating outside of the Americas (Clade ST198.2), while one was distantly clustered with isolates from South and North America (Clade ST198.1). The genomes of the two clade ST198.2 isolates encoded Salmonella Genomic Island 1 (SGI1), were multidrug‐resistant and encoded polymorphisms in the DNA gyrase (gyrA) and DNA topoisomerase (parC) known to confer resistance to fluoroquinolones. The single ST152 isolate was from raw beef, clustered with isolates from food and bovine sources in North America and was pan‐susceptible. Results of this study indicate that most S. Kentucky isolates from non‐human sources in Ireland are closely related ST314 and only a few isolates are antimicrobial‐resistant. This study also demonstrates the presence of multidrug‐resistant ST198 in food sources in Ireland.
Analytical Approximations for Dry Friction-Induced Stick–Slip and Pure-Slip Vibration Amplitudes of a Self-Excited Smooth and Discontinuous Oscillator
Authors: Yan Junfeng , Huang Zehao 
Published: October 2021

Abstract
An analytical and numerical investigation into pure-slip and stick–slip oscillations induced by dry friction between a rigid mass linked by an inclined spring, modeled by the archetypal self-excited smooth and discontinuous (SD) oscillator, and the classical moving rigid belt, is presented. The friction force between surface contacts is modeled in the sense of Stribeck effect to formulate the friction model that the friction force first decreases and then increases with increasing relative sliding speed. Some perturbation methods are considered into this system for establishing the approximate analytical expressions of the occurring conditions, vibration amplitudes, and base frequencies of dry friction-induced stick–slip and pure-slip oscillations. For pure-slip oscillations, two different approaches are applied to analyze this self-excited SD oscillator. One of them is the homotopy perturbation method by constructing the nonlinear amplitude and frequency. Based on the multiple-scales homotopy perturbation method, a nonlinear equation for amplitude of the analytical approximate solution is constructed, which containing all parameters of problem. For stick–slip oscillations, the analytical approximations for amplitude and frequency are obtained by perturbation methods for finite time intervals of the stick phase, which is linked to the subsequent slip phase under the conditions of continuity and periodicity. The accuracy of analytical approximations is verified by the comparison between analytical approximations and numerical simulations. These analytical expressions are needed for gaining a deeper understanding of dry friction-induced pure-slip and stick–slip oscillations for the friction system with geometric nonlinearity.
Analysis of Dynamic Characteristics of a Fractional-Order Spur Gear Pair With Internal and External Excitations
Authors: Hou Jing-Yu , Yang Shao-Pu , Li Qiang , Liu Yong-Qiang 
Published: October 2021

Abstract
The nonlinear frequency response characteristics of a spur gear pair with fractional-order derivative under combined internal and external excitations are investigated based on the incremental harmonic balance (IHB) method. First, a pure torsional vibration model is proposed that contains various complex factors, such as the time-varying mesh stiffness, transmission error, the fluctuation of input torque, backlash. Then, the IHB method is developed to calculate the higher-order approximate solution of the system, and the correctness of the results is verified by comparing with numerical simulation results obtained by the power series expansion (PSE) method. Furthermore, the types of various impact situations and their judgment conditions are discussed, and the different impact behaviors are analyzed in detail when ω∈[0, 1.5] by using phase diagrams and amplitude–frequency response curves. The influence of important parameters on the dynamic characteristics of gear pair is analyzed at last. The results indicate that the analytical solution derived by IHB method is sufficiently precise. Significantly, the dynamic characteristics of the system could be effectively controlled by adjusting time-varying mesh stiffness coefficient, the order and coefficient of fractional-order term, and the amplitude of internal excitation or external excitation. As a part of the theory of fractional-order mechanical system, the impact performance of fractional-order gear pair is approached for the first time by analytical method.
Fatigue Damage Management According to Performance-Based Maintenance Concept
Authors: Kamaya Masayuki 
Published: October 2021

Abstract
A maintenance concept of performance-based maintenance (PBM) has been proposed by the current author. According to the PBM concept, inspection results are considered in determining the next inspection schedule. In this study, this concept was applied to fatigue degradation for stainless steel components in the pressurized water reactor (PWR) primary water environment. It is possible to estimate the fatigue life for the PWR water environment from that obtained in an air environment and the parameter Fen, which represents the ratio of the fatigue life in the air and PWR water environments. It was shown that the fatigue life prediction using Fen can be replaced by the crack growth analysis using the growth rate for the PWR water environment. Then, the crack growth was predicted for a thermal loading assuming the growth occurred in the PWR water environment. It was shown that the duration until the next inspection could be optimized based on the inspection results together with the crack growth curve. A longer operation before the inspection assured a longer duration until the next inspection.
A necessary condition for discrete branching laws for Klein four symmetric pairs
Authors: He Haian 
Published: October 2021

We show a necessary condition for Klein four symmetric pairs [Formula: see text] satisfying the condition (D.D.); that is, there exists at least one infinite-dimensional simple [Formula: see text]-module that is discretely decomposable as a [Formula: see text]-module. This work is a continuation of [A criterion for discrete branching laws for Klein four symmetric pairs and its application to [Formula: see text], Int. J. Math. 31(6) (2020) 2050049]. Moreover, we define associated Klein four symmetric pairs, and we may use these tools to compute that a class of Klein four symmetric pairs do not satisfy the condition (D.D.); for example, [Formula: see text].
Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study
Authors: Ebbesen Magnus N. , D’Souza Maria , Andersson Charlotte , Butt Jawad H. , Madelaire Christian , Biering‐Sorensen Tor , Lock‐Hansen Morten , Kristensen Soren Lund , Gislason Gunnar , Kober Lars , Torp‐Pedersen Christian , Schou Morten 
Published: October 2021

Background
It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first‐degree family members with HF or dilated cardiomyopathy (DCM).

Methods and Results
Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre‐existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first‐degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5‐year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8–10.7] versus 5.6% [95% CI, 5.0–6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13–1.64]). (HF 8.4% [95% CI, 7.0–9.8] versus 4.5% [95% CI, 4.1–5.0]); (adjusted HR, 1.49 [95% CI, 1.22–1.82]). However, familial HF/DCM was not significantly associated with an increased 5‐year risk and rate of death (0.8% [95% CI, 0.4–1.2] versus 1.1% [95% CI, 0.8–1.3]); (adjusted HR, 0.80 [95% CI, 0.46–1.39]).

Conclusions
In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first‐degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5‐year incidence of HF compared with those without.